Open access peer-reviewed chapter

Factors of Nasopharynx that Favor the Colonization and Persistence of Staphylococcus aureus

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Samuel González-García, Aída Hamdan-Partida, Anaíd Bustos-Hamdan and Jaime Bustos-Martínez

Submitted: 05 July 2020 Reviewed: 05 January 2021 Published: 22 January 2021

DOI: 10.5772/intechopen.95843

From the Edited Volume

Pharynx - Diagnosis and Treatment

Edited by Xiaoying Zhou and Zhe Zhang

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Between 30 and 50% of the world population is permanently colonized in some anatomical site by Staphylococcus aureus, although the vast majority are asymptomatic carriers. The nose is its main niche and currently the colonization of S. aureus in the pharynx has become relevant due to the variety of reported carrier rates and the epidemiological importance of the dissemination of Methicillin-resistant S. aureus strains (MRSA) by pharyngeal carriers. For this bacterium to colonize a tissue successfully, it is necessary to establish many interactions with bacterial and host cell components such as bacterial wall teichoic acids (WTA) with the Scavenger SREC-1 host receptor and at the same time evade the defense mechanisms. On the other hand, there are host factors that will facilitate or complicate the colonization or persistence of S. aureus at these sites, such as physiological, genetic, immunological and microbiological factors.


  • Staphylococcus aureus
  • colonization
  • nasopharynx
  • microbiota
  • SREC-1

1. Introduction

Staphylococcus aureus is a Gram-positive bacterium that lives in symbiosis with humans, it is an opportunistic and potentially lethal pathogen [1, 2] of great clinical importance due to the different virulence, invasiveness and resistance factors that it may possess [3]. In humans, it colonizes various tissues, forming part of the normal microbiota [3, 4], although it is also one of the principal cause of community-associated and nosocomial-associated infections; is one of the main causes of bacteremia and infective endocarditis, as well as skin, soft tissue and pleuropulmonary infections and contamination of medical devices [4]. Invasive disease is associated with a mortality rate of ≥20% [2]. Uncontrolled use of antibiotics, particularly their inappropriate and excessive use, has favored the emergence and maintenance of strains of S. aureus resistant to multiple antibiotics such as penicillin (penicillin-resistant S. aureus, PRSA), methicillin (methicillin-resistant S. aureus, MRSA) [5, 6] or vancomycin, strains with high rates of morbidity and mortality in many countries of the world [5]. The most studied primary reservoir site for S. aureus in humans is the nose, predominantly found in the anterior nasal vestibule [7]. Approximately 30% or more of the world population is colonized with S. aureus on the skin, mucous membranes, or in the nose [4, 5] (Figure 1).

Figure 1.

S. aureus can cause a wide range of diseases by spreading to various tissues, among the survival mechanisms being the formation of biofilms regulated by several genes such as the accessory regulatory gene agr and by intracellular infection mechanisms (Modified from Sasegbon and Hamdy. [49]).

The mechanisms of colonization and persistence of S. aureus in the human nose have been extensively studied, however, it must be recognized that the clinical relevance of S. aureus carriers in the pharynx has not been sufficiently investigated [8]. This omission seems to be justified, if the nose is considered as the primary site of colonization of S. aureus, from there, other regions of the body are colonized by manual propagation [9]. However, in the adult population S. aureus can be commonly found in other parts of the body such as the armpits (8%), chest / abdomen (15%), perineum (22%), intestine (17–31%), vagina (5%) [10].

S. aureus carriers have been found in the pharynx and have been reported with high variability in different populations from 4 to 64% [11], some studies mention a higher rate of carriers in the pharynx than in the nose when samples are taken in parallel [10, 12, 13].

Colonization of S. aureus in the nose and pharynx is a multifactorial process that involves genetic aspects of the host, virulence factors of the pathogen, and possible interactions between the microbiota of the host [14], although in principle it is thinks that colonization of the pharynx is secondary to colonization of the nose, it is likely that both processes are independent [15].


2. Human determinants

The human determinants that allow bacterial colonization can be changes at the molecular level that alter the adhesiveness, recognition and eradication properties. Epidemiological studies present little information related to molecular studies [10].

The anterior nostrils are one of the main reservoir niches of S. aureus, however, the colonization of the nose begins from a cutaneous site, where the bacterium plays a role of commensal microbiota and, through contact with contaminated hands, spreads to the nose and other parts of the body [16].

Colonization of the nose begins a few days after birth [17]. Between 40 and 50% of newborns become carriers during the first eight weeks of life but decreases to 21% in the sixth month [18]. In another research, 80% of identical strains were found among mother–child pairs, and in 90% of newborns, S. aureus came from the maternal nose [16].

Days after birth, the hands are the main source of transmission of S. aureus from contaminated surfaces to the nose. Reagan et al. [19] demonstrated by means of a randomized, double-blind and placebo-controlled trial, the link between the passage from the hand to the nose of S. aureus, in addition they demonstrated that nasal decolonization with mupirocin decreased the carriage in the hands and nose [16].

Research in people living in the same household has found that they tend to carry genetically similar nasal strains, suggesting their horizontal transmission. Furthermore, it has been shown that the carriage of MRSA strains in various parts of the body increases the risk of nasal colonization by MRSA [16].

2.1 Overview of the nostrils

The nasal passage filters 95% of the particles with a diameter greater than 15 μm from the inspired air. The nose is extremely important in protecting the distal airways from the influence of gases, aerosols, and pathogens [20].

The anterior part of the nasal cavity (vestibulum nasi) is formed with stratified squamous epithelium, non-ciliated keratinized (60% of the strains of S. aureus originating from the nose are isolated in this part). It has also been shown that S. aureus can colonize and persist in ciliated nasal epithelial cells in the inner part of the nasal cavity (internal nostrils) with pseudostratified columnar ciliated epithelium [9, 14].

The epidermis and dermis are the two main layers that line the vestibulum nasi. The dermis is a connective tissue that contains both epidermal and lymphatic structures, and vascular ducts, nerves, nerve endings, collagen, and elastic fibers, as well as a wide variety of specialized immune cells [7].

The epidermis is made up of the basal, spiny, granular, lucid and corneal striatum [7]. These five main strata are characterized by cells in different stages of differentiation, during which the anterior nasal epithelial cells change their appearance to keratinized squamous anucleated cells called corneocytes, these cells form the stratum corneum (also called cornified layer) being the most external, they are also surrounded by a protein structure containing loricrin and involucrin (Figure 2) [7, 14]. The upper layers of the keratinized epithelium are constantly being replaced, which could contribute to the elimination of the attached bacteria, however, this does not happen [14].

Figure 2.

Nasal colonization sites of S. aureus. 1. Vestibulum nasi or nasal cavity, is the ecological niche of S. aureus in humans. S. aureus Has a large amount of adhesins such as ClfB (light blue line), IcaA (strong blue line), Spa (orange line), SdrC (green dots), FnBPA (pink triangle), which can bind to various proteins of the nasal epithelial cells such as keratin and loricrin (red line), involucrin (purple line), unknown receptors (black triangle), fibronectin (gray rectangle). 2. The inner part of the nasal cavity can also be colonized by S. aureus and survive for a long time, at this site it binds by multiple load interactions by the teichoic acids of the bacterial wall (WTA) with the SREC-1 nasal cell receptor. (modified from Sakr et al. [16]).

2.1.1 Loricrin

Epithelial tissues are the main appendages that protect the internal organs of the body from environmental stress, chemical damage, and microbial infections. The stratified epithelia seen on the skin and oral mucosa are one of the most resistant and protective epithelia, as it resists severe physical and chemical forces and do so by producing a hardened structure: the cornified cell envelope (CE). Loricrin is an important component of keratins. These keratins are structural proteins and constitute approximately 85% of a fully differentiated keratinocyte (Figure 3) [21, 22].

Figure 3.

Location of loricrin, involucrin, keratin and other macromolecules in mature corneocytes (modified from Ishitsuka and Roop. [21]).

Loricrin is an insoluble polypeptide with a molecular weight of 26 kDa. It has a conserved epitope and is a major cornified envelope protein seen in the cytoskeleton of the stratified parakeratinized epithelium. Being a late differentiating protein, it is introduced into the cornified envelope structure due to its cross-linking and binding property. It improves the function of the corneocyte protective barrier in differentiated keratinocytes [21].

Loricrin occupies an important part (70%) of the cornified epidermal envelope. Its concentration is reduced to approximately 30–50% in certain areas such as the palate and esophagus, while it is not expressed in many internal epithelia such as the oral mucosa. In in vivo studies in mammalian tissues, loricrin has a very high expression in all stratified epithelia, and is expressed even more in moist tissues of newborns such as the epidermis, foreskin, epidermal sweat ducts, in addition to the oral and anal mucosa and the esophagus [21, 22].

In vitro analysis and studies in animal models have revealed that the main colonization target ligand of S. aureus is loricrin, binding with clumpling factor B (ClfB) in squamous epithelial cells [23].

2.1.2 Involucrin

Involucrin is a soluble cytosolic protein that is the precursor of the cornified envelope, its main function is to donate a glutamyl or glutamine in the crosslinking reaction catalyzed by the enzyme transglutaminase and it disappears from the soluble phase after the activation of calcium-dependent transglutaminase. 20% of its structure is glutamate and 25% glutamine. An important biochemical characteristic of involucrin is that it contains a central domain composed of 39 tandem repeats of 10 amino acids each segment, this repetitive structure is conserved in the involucrins of all higher primates, only varying the number of repeats [24]. In the cornified structure, involucrin is adjacent to the cell membrane, when the cell membrane is replaced, involucrin is the main substrate to which lipids esterify, primarily ceramides, are covalently attached to form the outer surface of the cornified envelope (Figure 3) [25].

The iron-regulated surface determining protein (IsdA) promotes the adhesion of S. aureus to squamous cells that cooperate in binding to the cornified cell envelope with the host proteins loricrin, involucrin, and cytokeratin [26].

2.1.3 Cytokeratine 10 (K10)

In the epidermis, keratinocytes travel from the basal cell layer to the postmitotic spinous suprabasal cells, and during the process, there is a significant change in the expression of basal cell keratins (K5, K14, and K15) to suprabasal epidermal keratins first to type II K1 keratin and later to type I K10 keratin. The keratin filaments are structurally composed of the K1 / K10 pair and form dense bundles, characteristic of suprabasal epidermal keratinocytes, and this gives the cells and the entire epidermis mechanical integrity (Figure 3). However, there are more functionalities, as K10 has been shown to specifically inhibit the proliferation and progression of the keratinocyte cell cycle and the decrease in K10 leads to an increase in keratinocyte renewal [27, 28].

It has been shown that cytokeratin 10 is a receptor for ClfB of S. aureus, which facilitates the nasal colonization of this and other bacteria [29].

2.2 Interactions with the nasal cavity

Another ecological niche of S. aureus in addition to the vestibulum nasi is the internal part of the nasal cavity (Figure 2). The teichoic acids of the bacterial wall (WTA) are a principal factor for the colonization process. A study reported in an animal model that mutated strains deficient in the tagO and tarK genes that participate in WTA biosynthesis did not adhere to or colonize the nose cells of cotton rats compared to control bacteria [14].

Baur et al. [30] re-studied the adhesion to nasal cells of WTA and reported the expression of the SREC-1 receptor (from the family of Scavenger receptors type F) in the nose of cotton rats and in epithelial cell lines of the human internal nasal cavity. In addition, they found that SREC-1 interacts with WTA and verified it in cotton rats infected with a previous treatment with anti-SREC-1 antibodies, significantly decreasing colonization after 8 hours and 6 days after inoculation compared to the control group.

2.2.1 SREC-1 receptor

The key role that WTA plays in the early colonization stages of S. aureus has been demonstrated, however, until recently the ligand with which it binds to initiate adhesion and colonization with the host was found.

The Scavenger receptor superfamily can bind and endocyte many ligands, which causes the elimination of both exogenous and unnecessary endogenous molecules [31]. It is important to mention that the affinity for the ligands is shared by several Scavenger receptors, regardless of whether their classes (A-J) have little or no biochemical homology [31, 32].

The Scavenger 1 class F receptor (SREC-1, SCARF1 or SR-F1), is the most expressed by endothelial cells (of the Scavenger family). It is a type I transmembrane protein that weighs 86 kDa, contains some epidermal growth factors (EGF) with similarity to the extracellular region, a small transmembrane domain, and a long cytoplasmic tail rich in proline and serine [33].

The size of the cytoplasmic domains could have a role in intracellular signaling, however, this function has not been found. SREC-1 is an evolutionarily highly conserved receptor, particularly in the extracellular domain, and shows significant homology with the Caenorhabditis elegans Scavenger receptor CED-1, important in homeostasis and innate immunity of C. elegans [34].

SREC-1 was obtained from human umbilical vein endothelial cells (HUVEC), but its expression has been reported in multiple cells, including epithelial cells [30], sinusoidal endothelial cells [33, 35], dendritic cells, B-1 cells. [36] and macrophages [35, 36]. It is important to mention that almost all studies focused on the functionality of this receptor have used transfected cell lines, designed to express the receptor extracellularly in vitro, and some studies have used cells that naturally express the SREC-1 receptor in vivo [33]. Furthermore, the first reports of the expression of this receptor showed high transcriptional expression in multiple human tissues such as spleen, lung, heart, liver, and kidney and it has been corroborated in murine tissues [33, 36]. However, more studies are needed to investigate its expression and cellular distribution at the protein quantity in these tissues. So far, there is only one study that has fully characterized the cellular distribution and expression of the SREC-1 receptor in healthy and chronically ill human liver [35]; therefore, much remains to be studied to understand the activity of this receptor in human cells and tissues [33].

2.3 Individual host factors favoring nasal colonization of S. aureus

Some studies have found that S. aureus nasal carriers are more common in people infected with the Human Immunodeficiency Virus (HIV) [37] and obese patients [38], compared to healthy individuals. Nowak et al. [39] ​​published the positive correlation between percentage of body mass and susceptibility to colonization by S. aureus in healthy male individuals. This high prevalence was also reported in diabetic dialyzed patients, compared with non-diabetic patients [16]. Other diseases such as granulomatosis with rheumatoid arthritis, skin and soft tissue infections [40], atopic dermatitis, and recurrent furunculosis have been associated with an increased carrier rate [16].

Contrary to what was reported by Nowak et al. [39], Liu et al. [41] found similar percentages of carriers in women and men, however, men had a higher density of bacteria. To date, it has not been confirmed that hospital workers are at increased risk of being nasal carriers of S. aureus compared to the rest of the population [42, 43]. The association between nasal carriers of S. aureus and smoking is controversial, Olsen et al. [44], reported that healthy active smokers are protected from becoming carriers of S. aureus, due to the possible antibacterial activity of tobacco. However, another experimental inoculation study showed that smokers are colonized more frequently than non-smokers and that quitting smoking improves clearance of S. aureus nasal [45]. Other host pathologies, such as hormonal contraception [46], have also been extensively studied, and the presence of hemoglobin in nasal secretions has been reported as an additional predisposing factor [16].

Regarding host genetics, no significant heritability data has been detected for nasal colonization of S. aureus in twins and family studies [47, 48]. However, some polymorphisms have been found in genes involved in inflammatory processes and have been associated with the carriage of S. aureus in the nose, for example, the phenotype of the histocompatibility antigen HLA-DR3 could be a predisposition [16].

The host cell presents modified carbohydrates and secretes surface proteins, such as blood group antigens, which are involved in bacterial adhesion and colonization. An investigation found that people with blood group O have a 6.5 times higher risk of being carriers of S. aureus in the pharynx, compared to people with blood group A [9].

2.4 Overview of the pharynx

The pharynx is a muscular chamber that serves the respiratory and digestive systems to receive air for the nasal cavity and food and water for the oral cavity [49]. The oropharynx consists of five layers: mucosa, submucosa, pharyngobasilar fascia, constrictor muscle, and oropharyngeal fascia [50]. The pharynx has stratified non-ciliated epithelium that secretes mucus with mucin. Specifically, the posterior wall of the oropharynx (and the soft palate) is lined by a nonkeratinized stratified squamous epithelium, supported by an underlying lamina propria and a muscular layer. In the palatal and lingual tonsil regions, there are nodules of lymphoid tissue located below the epithelium, each tonsil is in a fixed position, in other regions there are membrane-associated lymphoid tissue [MALT], found throughout the body. The structural support is mainly provided by reticular fibers composed of type III collagen. These fibers condense and combine with elastin fibers to form septa that dissect the tonsillar parenchyma [50]. S. aureus can bind to multiple ligands of the pharynx such as collagen, fibronectin, fibrinogen through adhesin proteins such as Cna, FnBa, FnBb, among others (Figure 4) [16].

Figure 4.

Colonization of S. aureus in the human pharynx. S. aureus Competes directly with bacteria that predominantly colonize the pharynx; it is known that bacteria such as Streptococcus pneumoniae, Streptococcus mutans, Streptococcus mitis, among others, inhibit the growth of S. aureus. Regarding the colonization mechanism, so far only the same ones as in the nose have been studied, for example, their binding to fibrinogen, fibronectin, collagen, among other proteins expressed in both anatomical sites, however, they have not been analyzed in depth its specific interactions with the pharynx.

The oropharynx links the mouth, nasopharynx, lower respiratory tract, and gastrointestinal tract and is always exposed to a large number of microorganisms, both exogenous and endogenous. The set of species to be studied is wide, since there are very diverse bacterial communities in both adults and the elderly. The pharynx is also a niche for pathogenic bacteria that can cause localized (pharyngitis) or disseminated disease (primarily lung disease or systemic if spread) [51].

2.4.1 Importance of the study of S. aureus in the pharynx

The pharynx has recently been identified as a potential colonization site for S. aureus, this colonization can occur in the presence or absence of nasal colonization [52]. Being a carrier of S. aureus in the pharynx has potentially important implications in decolonization strategies for populations at high risk of infection, it is unlikely that topical drugs aimed at eradicating nasal colonization affect transport in the throat, therefore which could be an important focus in future infections if S. aureus persists in the pharynx [53].

Most of the S. aureus detections, in particular MRSA, are only made from nasal swabs, since the pharyngeal swab is not considered a standard, Mertz et al. [54] mention that some drawbacks of pharyngeal exudate is causing discomfort to the patient and that it increases the cost to the health care system without significantly greater sensitivity. However, as mentioned above, pharyngeal colonization may be more common than nose colonization than has been published.

The rate of nasal carriers of MRSA in hospital patients has been found to be 5.9 to 15.6%, however, the rate of pharyngeal MRSA carriers is between 10 and 23.1%, which represents a greater number of carriers in the pharynx [55].

Cirkovic et al. [56] conducted a study of carriers and genetic diversity of MRSA in 195 hospitalized patients and 105 workers of a University Hospital in Serbia and reported a rate of 32.2% of exclusive MRSA carriers in the nose and another 32.2% of exclusive carriers of the pharynx, in addition of 35.5% of MRSA carriers in both sites, so the exclusion of pharyngeal exudates would result in a significant error in a substantial part of this work, since around a third are MRSA carriers exclusive to the pharynx [12, 13].

2.4.2 Interaction of S. aureus with the microbiota

Pathogenic bacteria can coexist with their host in two ways, as harmless microbiota microorganisms or as invading pathogens that enter healthy tissues after overcoming innate defense mechanisms or if the immune system is compromised [57]. Despite microbiology studies regarding infection mechanisms, ecological studies of pathogenic microorganisms present in the human microbiota are still lacking [58].

In vitro and in vivo studies that simulate colonization by S. aureus, as well as analysis of microbiomes and metagenomes reveal that the nose presents an intermediate level of bacterial diversity compared to the human oral cavity and intestine, but they present greater diversity than the vagina, which has less diversity. A percentage of the human population carries several bacterial species in the nose, such as Finegoldia magna, Dolosigranulum pigrum and Salmonella spp., are negatively correlated with colonization by S. aureus [41, 59]. It is not known how the nasal microbiota can prevent S. aureus colonization. Understanding this mechanism can help to understand why about 30% of the human population is persistently colonized by S. aureus, another 30% is highly resistant to nasal colonization by S. aureus, and the remainder are considered intermittent carriers [58].

2.4.3 Nasal microbiota

The nasal cavity of humans harbors a diverse bacterial community that is in principle stable at the gender level [41, 59, 60], but may vary between individuals and with season [61] In the same way, other places in the human body that are exposed to the environment are the skin and the oropharynx [61, 62, 63]. The dynamics of the nasal microbiota have not yet been analyzed. The analysis of the nasal microbiota is performed by amplification and sequencing of the 16S rRNA gene, that in many cases it is not possible to distinguish between species, therefore should implement shotgun metagenome sequencing techniques [58].

Many species of nasal bacteria are anaerobic [64], indicating that part of the nasal epithelium is barely exposed to air in the nasal cavity. Many species cannot be cultivated in vitro, they require special growth conditions [58].

Bacteria in the nose belong mainly to three phyla (Actinobacteria, Firmicutes, and Proteobacteria) and 80% humans or more are colonized with Corynebacterium spp., Propionibacterium spp., and Staphylococcus spp. [62, 65, 66]. Other genera are found less frequently [41].

Based on the abundance of characteristic species in the human nose, seven types of community status (CST) have been defined. (CST), each of which represents a nasal bacterial community dominated by S. aureus (CST1), Enterobacteriaceae (Escherichia spp., Proteus spp., Klebsiella spp. and others; CST2), S. epidermidis (CST3), Propionibacterium spp. (CST4), Corynebacterium spp. (CST5), Moraxella spp. (CST6) or Dolosigranulum spp. (CST7) [41]. S. aureus was found in several CSTs, although much less frequently than in CST1 [58].

During the first years of life, the microbiota of the respiratory tract develops [67, 68]. The oral microbiota is similar to that of the skin, but is less similar to that of the oral cavity. So the nose could be an intermediate step between these two niches [62]. The microbiota of the sebaceous and moist areas of the skin is more similar to that of the nose than to the dry areas of the skin [61]. Streptococcus spp. is abundant in the oral cavity, but it is found in low numbers in the nose [69]. Species of Coagulase-negative Staphylococcus (SCN), such as Staphylococcus capitis, Staphylococcus warneri, Staphylococcus hominis, and Staphylococcus lugdunensis, are prevalent on the skin, but they are only found in the nasal cavity of some people, with the exception of S. epidermidis, which colonizes both the nose and the skin of most people [58]. Factors influencing composition of the nasal microbiota

Bacterial communities in the nose undergo seasonal variations, mainly during the change from winter to spring [70]. The environment plays an important role in the composition of the nasal microbiota as factors such as humidity, temperature, dust or pollen influence [41, 70]. Furthermore, smoking has been shown to prevent nasal colonization by S. aureus [44], although it is still under discussion [45]. Some studies have shown that the gender and genetic composition of the host have a moderate influence on the colonization of S. aureus, however the type of nasal microbiota seems to be an important factor for the colonization of this bacterium [41, 48]. Furthermore, nasal colonization by S. aureus hardly varies between humans of different ethnic and geographic origins [70]. The various regions of the nose, from the anterior vestibule to the sphenoethmoidal recess in the posterior nasal cavity, are lined with mucus, thus differing in the composition of the microbiota between individuals [60].

Metagenomic studies have shown the importance of the role of bacteriophages in the dynamics of the microbiota of the skin and intestine [71]. In the human nose the abundance and diversity of bacteriophages have not yet been analyzed, they can alter the nasal microbiota. Bacteriophages are one of the main mechanisms for horizontal transfer of virulence and antibiotic resistance genes between staphylococci and other bacteria, which can contribute to the appearance of new strains [72]. Competition for nutrients

Unlike the gastrointestinal microbiota, bacteria in the nasal cavity do not interact with food in the diet and can only acquire nutrients that are excreted by cells, so nasal secretions contain few nutrients [73] and are has hypothesized that bacteria in the nasal microbiota compete for scarce nutrients. Nasal secretions contain NaCl in physiological concentrations (~ 150 mM) and low levels of potassium, magnesium, and phosphate. Carbohydrates, amino acids, and other nutrients are found in nasal secretions in much lower amounts than those found in plasma [58]. There is a synthetic nasal medium (SNM), containing nutrients in the same amounts as in nasal fluid, allowing S. aureus to develop, but most SCNs cannot grow under these conditions or grow very slowly [73]. This would indicate that most of the SCNs present in the nose are only transitory and are not a permanent colonization site for these bacteria. Many of the genes involved in the nutrient absorption systems and anabolic metabolic pathways in S. aureus are highly expressed in NMS or in the nose [73]. S. aureus is successful when it competes with other nasal microorganisms as it depends on its ability to grow in low amounts of nutrients. Nasal bacteria do not always compete with other bacteria for nutrients, in certain cases they can also cooperate with others to obtain specific nutrients, such as S. aureus and Corynebacterium accolens that seem to have a mutualistic relationship [60].

The main carbohydrate in nasal fluids is glucose and it is found in low concentrations (between 35 μM and 1 mM, with an average value of ~370 μM) [73] which depends on the nutritional status of the person. The colonized by S. aureus is higher in diabetic people, perhaps due to high concentrations of nasal glucose. Sialic acids, which line the membrane of eukaryotic cells, can be an important source of energy for bacteria in the nasal cavity [58]. Many bacteria can metabolize sialic acids how S. aureus and some SCNs including S. intermedius, S. lugdunensis, and S. saprophyticus, but not S. epidermidis, can absorb and use sialic acid [74].

S. aureus is the only one of the staphylococci that can degrade the main phosphatidylcholine group that is released from eukaryotic cells, extracellular glycerophosphocholine (GroPC). S. aureus can grow with GroPC as the sole carbon source so it can survive in limited nutrient conditions [58].

Nasal fluids contain several of the 20 amino acids necessary for protein biosynthesis in concentrations between 10 μM and 250 μM; however, several such as methionine, tyrosine, aspartate, asparagine, glutamine, and isoleucine are found in very low concentrations [73] so they need to be synthesized by nasal bacteria. This was verified since a mutant of S. aureus that presents a deficiency in the synthesis of methionine was isolated and this affected its growth in the cotton rat nasal colonization model [14, 73]. In certain sites of the nose, the concentrations of amino acids and peptides may be higher, S. aureus and other nasal bacteria secrete proteases that can degrade host proteins, which are found in high concentrations in nasal fluids, such as albumin, lactoferrin, mucins, cytokeratin 10, and hemoglobin [75]. S. aureus produces approximately ten extracellular proteases, which makes it different from most other nasal bacteria that do not produce extracellular proteases or produce only a few [76].

Nasal discharge, in addition to being low in nutrients, is also poor in essential metal ions such as zinc, manganese, iron, and other host proteins such as calprotectin and lactoferrin, which sequester these ions from the nasal cavity to prevent bacterial growth [75]. Because of this, the microbiota needs specific mechanisms to compete with the host’s defense, known as “nutritional immunity” [58].

When the growth of nasal bacteria slows due to a lack of nutrients, some bacteria produce antimicrobial substances to inhibit competing bacteria, these antimicrobial substances are normally ribosomally synthesized and post-translationally modified peptides (RiPP) or nonribosomal peptide-synthetase (NRPS) enzymes. Bacteria that produce these molecules are protected from specific immunity. Antimicrobial RiPPs (called bacteriocins) sometimes have a limited range of activity and are produced against specific groups of nasal bacteria. Most bacteriocins in nasal bacteria show changes such as thiazole heterocycles, lanthionine bridges (lantibiotics), and oxazole (microkines) or pyridine rings (thiopeptides) [77]. There are not many reports of bacteriocins in bacterial species isolated from the human nose [78].

Nasal strains of Staphylococcus spp. were studied for antimicrobial substances and found to be produced with a high frequency (86%) and a wide diversity of activities against groups of nasal bacteria. Due to this, bacteriocins can play a very important role in the formation of the nasal microbiota. Most members of Firmicutes and Proteobacteria are unaffected by the inhibitory activities of staphylococci, except Dolosigranulum pigrum and Moraxella catarrhalis. However, some bacteria of the phylum Actinobacteria, such as Corynebacterium pseudodiphtheriticum and Micrococcus luteus, were inhibited by staphylococcal bacteriocins [79]. These susceptible bacteria may be the main competitors of nasal staphylococci [58]. Most of the staphylococcal genes used in bacteriocin biosynthesis are found in mobile genetic elements forming part of plasmids or on the bacterial chromosome, which undergo extensive genetic rearrangements and horizontal gene transfer [79].

Bacteriocins have a wide variation in amino acid sequence, which can cause changes in the spectrum of activity [80, 81]. Due to this, the evolutionary process could have increased and changed the type of nasal bacteria, causing changes in the composition of the microbiota. This is the case with thousands of genes that produce secondary metabolites, many of which are potential antimicrobial substances. In investigations of the human metagenome of different surfaces of the human body, it was found that antimicrobial peptides can play an important role in the maintenance of the human microbiota [81]. In an investigation of nasal strains, S. epidermidis strains were found to be the main antimicrobial-producing bacteria, while S. aureus rarely produces these substances. The production of various antimicrobials is favored by stressful conditions during colonization, such as iron limitation or the presence of hydrogen peroxide (H2O2), indicating that many antimicrobials are tightly regulated [79].

Most staphylococcal bacteriocins are inactive for S. aureus. But, S. lugdunensis can synthesize an antimicrobial compound called lugdunin that inhibits and kills S. aureus. Lugdunin is encoded by the bacterial genome and is the first identified antimicrobial NRP produced by a human commensal bacterium, and represents a new class of cyclic peptide antibiotics containing thiazolidine. The lugdunin production operon is present in almost all nasal strains of S. lugdunensis, allowing this bacterium to compete with and kill S. aureus. People colonized by S. lugdunensis have a six times lower risk of being carriers of S. aureus than people who are not colonized [82]. Similarly, SCNs that produce certain bacteriocins can prevent S. aureus from colonizing the skin in patients with atopic dermatitis [83]. These results show the importance of the production of antimicrobial compounds by commensal bacteria that can prevent colonization by pathogenic bacteria such as S. aureus [58]. Another enzyme called lysostafin that is produced by Staphylococcus simulans could degrade the cell wall of multiple species of staphylococci, including S. aureus, by hydrolyzing the pentaglycine bonds that bind peptidoglycan [84].

Other bacteria in the nose use indirect methods to inhibit the growth of competing bacteria, such as S. pneumoniae, which is found mainly in the throat and rarely in the nose, but colonization by S. pneumoniae prevents colonization of the nose by S. aureus [58]. Possibly, this inhibition may be due to the release of hydrogen peroxide, a metabolite produced by S. pneumoniae that produces the generation of free radicals that damage DNA, and which also activates the prophages contained in the genome of S. aureus strains, which that causes the lysis of bacteria [85]. Also, S. pneumoniae can interfere with S. aureus in other ways, such as by inducing cross-reactive antibodies that prevent S. aureus colonization [86]. Viridans group streptococci (S. mitis, S. sanguis, S. oralis, S. mutans, and S. sobrinus) have also been found to prevent MRSA colonization of the pharynx in newborns, due to bacteriocin activity of peroxidase type [87].

2.5 Pharyngeal microbiota

In the nasal, oral and pharyngeal human cavities live hundreds of microbial species, including between 25 and 40 families archeas, bacteria, amoebae and fungi, as evidenced in a wide range of cultures. The number of newly discovered species has increased considerably due to the discovery of noncultivable species [88]. A data published in the Human Microbiome Project (HMP), 5 main bacterial phyla have been identified in the pharynx: Firmicutes, Proteobacteria, Bacteroidetes, Fusobacteria and Actinobacteria. Interestingly, the pharyngeal microbiome is distinguished from other parts of the body (intestines, skin and vagina) by having more Bacteroidetes. The proportion of bacterial phyla in the pharyngeal microbiome comprises 27% of Bacteroidetes and only 10% of Proteobacteria, compared to the salivary microbiome, whose proportion corresponds to 9% of Bacteroidetes and 51% of Proteobacteria. These two phyla are mentioned because they are the main pathogens in human infections, for example, periodontitis is caused by Bacteroidetes and the most common Gram-negative pathogens (Acinetobacter, Moraxella, Pseudomonas, Haemophilus, Klebsiella, and Legionella spp) [89]. However, the two genera that dominate the micro-ecosystem of the pharynx are Streptococcus and Prevotella [90].

2.5.1 The pharyngeal microecosystem

The most common bacterial genera in the human pharynx are Prevotella, Capnocytophaga, Campylobacter, Veillonella, Streptococcus, Neisseria, Haemophilus, which represent 9.72% to 1.26% of the bacteria in the normal microbiome, according to HMP data. [89, 90]. As there are few studies of the pharyngeal microbiome, many interactions between the components of the microecosystem are not clear, however, the interactions of microorganisms with factors of the local environment are characteristic of the microbiome. From the above, it can be assumed that the pharyngeal microbiome may share common characteristics of other human microbiomes [89].

2.5.2 Potential roles of the pharyngeal microbiome

Animals have developed strategies that allow them to evade the invasion of microbial pathogens and humans are no exception. Therefore, the one inhabited by commensal microorganisms that participate as defenders has a fundamental action to comply with these strategies. However, the role of the pharyngeal microbiome in respiratory tract infections (RTIs) is not fully understood, there is evidence to suggest a protective effect, like the gut microbiome [89].

The pharynx microbiome plays a crucial role in lining the mucosa of the respiratory tract by protecting against infections by airborne pathogens, in addition to the immune mechanisms of the host, particularly against emerging infectious agents [89, 91].

Homeostasis of the pharyngeal microbiome is necessary to prevent infections caused by native bacterial species, which allows the abundant development of each species. Many pathogenic species can adapt well to the pharyngeal ecosystem and become established in the resident microbiome, rendering the host asymptomatic (such as S. aureus, H. influenza, and Mycoplasma pneumoniae) [92]. In epidemiological studies it has been suggested that the proportion of resident pathogens varies seasonally, as does the incidence of RTIs attributed to them [93].


3. Conclusions

S. aureus is an important clinical pathogen for humans that has developed the ability to bind to various components of the extracellular matrix of a wide range of cells and has generated mechanisms that allow its survival and persistence in adverse conditions such as the formation of biofilms. and intracellular infection, which overwhelmingly evades the host’s immune response in various human tissues.

On the other hand, it has also been possible to integrate with other important bacterial communities of the nose and skin to form part of the normal microbiome of these sites, but it can also survive in other tissues where it is not considered a normal microorganism, as is the case of the pharynx or intestines.

Although there are many studies of the colonization mechanisms and interactions of S. aureus in the nose, there is little information on the processes and interactions that it performs in the pharynx. Therefore, additional studies of the pharynx as a site of colonization of S. aureus are required.



This work was support by Special Research Support Program of UAM.


Conflict of interest

The authors declare no conflict of interest.


  1. 1. Brown AF, Leech JM, Rogers TR, McLoughlin RM. Staphylococcus aureus colonization: modulation of host immune response and impact on human vaccine design. Front Immunol 2014;4:1-20. DOI: 10.3389/fimmu.2013.00507
  2. 2. Mistretta N, Brossaud M, Telles F, Sanchez V, Talaga P, Rokbi B. Glycosylation of Staphylococcus aureus cell wall teichoic acid is influenced by environmental conditions. Sci Rep 2019;1:1-11. DOI: 10.1038/s41598-019-39929-1
  3. 3. Kadariya J, Thapaliya D, Bhatta S, Mahatara RL, Bempah S, Dhakal N, et al. Multidrug-resistant Staphylococcus aureus Colonization in Healthy Adults Is more Common in Bhutanese Refugees in Nepal than Those Resettled in Ohio. Biomed Res Int 2019;2019:1-11. DOI: 10.1155/2019/5739247
  4. 4. Tong SYC, Davis JS, Eichenberger E, Holland TL, Fowler VG. Staphylococcus aureus infections: epidemiology, pathophysiology, clinical manifestations, and management. Clin Microbiol Rev 2015;3:603-61. DOI: 10.1128/CMR.00134-14
  5. 5. Khairalla AS, Wasfi R, Ashour HM. Carriage frequency, phenotypic, and genotypic characteristics of methicillin-resistant Staphylococcus aureus isolated from dental health-care personnel, patients, and environment. Sci Rep 2017;7:1-16. DOI: 10.1038/s41598-017-07713-8
  6. 6. Rodríguez-Lázaro D, Oniciuc EA, García PG, Gallego D, Fernández-Natal I, Dominguez-Gil, et al. Detection and characterization of Staphylococcus aureus and methicillin-resistant S. aureus in foods confiscated in EU borders. Front Microbiol 2017;8:1-10. DOI: 10.3389/fmicb.2017.01344
  7. 7. Hanssen AM, Kindlund B, Stenklev NC, Furberg AS, Fismen S, Olsen RS, et al. Localization of Staphylococcus aureus in tissue from the nasal vestibule in healthy carriers. BMC Microbiology 2017;17:1-11. DOI: 10.1186/s12866-017-0997-3
  8. 8. van Belkum A, Verkaik NJ, De Vogel CP, Boelens HA, Verveer J, Nouwen JL, et al. Reclassification of Staphylococcus aureus nasal carriage types. J Infect Dis 2009;199: 1820-6. DOI: 10.1086/599119
  9. 9. Nurjadi D, Lependu J, Kremsner PG, Zanger P. Staphylococcus aureus throat carriage is associated with ABO−/secretor status. J Infect 2012;65:310-7. DOI: 10.1016/j.jinf.2012.05.011
  10. 10. Sollid JUE, Furberg AS, Hanssen AM, Johannessen M. Staphylococcus aureus: determinants of human carriage. Infect Genet Evol 2014;21:531-41. DOI: 10.1016/j.meegid.2013.03.020
  11. 11. Mertz D, Frei R, Jaussi B, Tietz A, Stebler C, Flückiger U, et al. Throat swabs are necessary to reliably detect carriers of Staphylococcus aureus. Clin Infect Dis 2007;45:475-7. DOI: 10.1086/520016
  12. 12. Hamdan-Partida A, Sainz-Espuñes T, Bustos-Martínez J. Characterization and persistence of Staphylococcus aureus strains isolated from the anterior nares and throats of healthy carriers in a Mexican community. J Clin Microbiol 2010;48:1701-5. DOI: 10.1128/jcm.01929-09
  13. 13. Hamdan-Partida A, González-García S, de la Rosa García, E, Bustos-Martínez J. Community-acquired methicillin-resistant Staphylococcus aureus can persist in the throat. Int J Med Microbiol 2018;308:469-75. DOI: 10.1016/j.ijmm.2018.04.002
  14. 14. Weidenmaier C, Goerke C, Wolz C. Staphylococcus aureus determinants for nasal colonization. Trends Microbiol 2012;20:243-50. DOI: 10.1016/j.tim.2012.03.004
  15. 15. Hanson BM, Kates AE, Mills E, Herwaldt LA, Torner JC, Dawson JD, et al. The Oropharynx as a Distinct Colonization Site for Staphylococcus aureus in the Community. bioRxiv 2017;137901. DOI: 10.1101/137901
  16. 16. Sakr A, Brégeon F, Mège JL, Rolain JM, Blin O. Staphylococcus aureus nasal colonization: an update on mechanisms, epidemiology, risk factors, and subsequent infections. Front Microbiol 2018;9:1-15. DOI: 10.3389/fmicb.2018.02419
  17. 17. Maayan-Metzger A, Strauss T, Rubin C, Jaber H, Dulitzky M, Reiss-Mandel A, et al. Clinical evaluation of early acquisition of Staphylococcus aureus carriage by newborns. Int J Infect Dis 2017);64:9-14. DOI: 10.1016/j.ijid.2017.08.013
  18. 18. Peacock SJ, Justice A, Griffiths D, De Silva GDI, Kantzanou MN, Crook, D, et al. Determinants of acquisition and carriage of Staphylococcus aureus in infancy. J Clin Microbiol 2003;41:5718-25. DOI: 10.1128/jcm.41.12.5718-5725.2003
  19. 19. Reagan DR, Doebbeling BN, Pfaller MA, Sheetz CT, Houston AK, Hollis RJ, Wenzel R P. Elimination of coincident Staphylococcus aureus nasal and hand carriage with intranasal application of mupirocin calcium ointment. Ann Intern Med 1991;114:101-6. DOI: 10.7326/0003-4819-114-2-101
  20. 20. Beule AG. Physiology and pathophysiology of respiratory mucosa of the nose and the paranasal sinuses. GMS Curr Top Otorhinolaryngol Head Neck Surg 2010;9:1-24. DOI: 10.3205/cto000071
  21. 21. Ishitsuka Y, Roop DR. Loricrin: Past, Present, and Future. Int J Mol Sci 2020;21:1-28. DOI: 10.3390/ijms21072271
  22. 22. Nithya S, Radhika T, Jeddy N. Loricrin–an overview. J Oral Maxillofac Pathol 2015;19:64-8. DOI: 10.4103/0973-029X.157204
  23. 23. Mulcahy ME, Geoghegan JA, Monk IR, O'Keeffe KM, Walsh EJ, Foster TJ, et al. Nasal colonisation by Staphylococcus aureus depends upon clumping factor B binding to the squamous epithelial cell envelope protein loricrin. PLoS Pathog 2012;8:1-14. DOI: 10.1371/journal.ppat.1003092
  24. 24. Yaffe MB, Beegen H, Eckert RL. Biophysical characterization of involucrin reveals a molecule ideally suited to function as an intermolecular cross-bridge of the keratinocyte cornified envelope. J Biol Chem 1992;267:12233-8.
  25. 25. Candi E, Schmidt R, Melino G. The cornified envelope: a model of cell death in the skin. Nat Rev Mol Cell Biol 2005;6:328-40. DOI: 10.1038/nrm1619
  26. 26. Foster TJ, Geoghegan JA, Ganesh VK, Höök M. Adhesion, invasion and evasion: the many functions of the surface proteins of Staphylococcus aureus. Nat Rev Microbiol 2014;12:49-62. DOI: 10.1038/nrmicro3161
  27. 27. Moll R, Divo M, Langbein L. The human keratins: biology and pathology. Histochem Cell Biol 2008;129:705-33. DOI: 10.1007/s00418-008-0435-6
  28. 28. Kumar A, Jagannathan N. Cytokeratin: A review on current concepts. Int J Orofac Biol 2018;2:6-11. DOI: 10.4103/ijofb.ijofb_3_18
  29. 29. Trivedi S, Uhlemann AC, Herman-Bausier P, Sullivan SB, Sowash MG, Flores EY, et al. The surface protein SdrF mediates Staphylococcus epidermidis adherence to keratin. J Infect Dis 2017;215:1846-54. DOI: 10.1093/infdis/jix213
  30. 30. Baur S, Rautenberg M, Faulstich M, Grau T, Severin Y, Unger C, et al. A nasal epithelial receptor for Staphylococcus aureus WTA governs adhesion to epithelial cells and modulates nasal colonization. Plos Pathog 2014;10:1-13. DOI: 10.1371/journal.ppat.1004089
  31. 31. Canton J, Neculai D, Grinstein S. Scavenger receptors in homeostasis and immunity. Nat Rev Immunol 2013;13:621-34. DOI: 10.1038/nri3515
  32. 32. Zani IA, Stephen SL, Mughal NA, Russell D, Homer-Vanniasinkam S, Wheatcroft SB, et al. Scavenger receptor structure and function in health and disease. Cells 2015;4:178-201. DOI: 10.3390/cells4020178
  33. 33. Patten DA. SCARF1: a multifaceted, yet largely understudied, scavenger receptor. Inflamm Res 2018;67:627-32. DOI: 10.1007/s00011-018-1154-7
  34. 34. Means TK, Mylonakis E, Tampakakis E, Colvin RA, Seung E, Puckett L, et al. Evolutionarily conserved recognition and innate immunity to fungal pathogens by the scavenger receptors SCARF1 and CD36. J Exp Med 2009;206:637-53. DOI: 10.1084/jem.20082109
  35. 35. Patten DA, Kamarajah SK, Rose JM, Tickle J, Shepherd EL, Adams DH, et al. SCARF-1 promotes adhesion of CD4+ T cells to human hepatic sinusoidal endothelium under conditions of shear stress. Sci Rep 2017;7:1-15. DOI: 10.1038/s41598-017-17928-4
  36. 36. Ramirez-Ortiz ZG, Pendergraft III WF, Prasad A, Byrne MH, Iram T, Blanchette CJ, et al. The scavenger receptor SCARF1 mediates the clearance of apoptotic cells and prevents autoimmunity. Nat Immunol 2013;14:917-26. DOI: 10.1038/ni.2670
  37. 37. Kotpal R, Bhalla P, Dewan R, Kaur R. Incidence and risk factors of nasal carriage of Staphylococcus aureus in HIV-infected individuals in comparison to HIV-uninfected individuals: a case–control study. J Int Assoc Provid AIDS Care 2016;15:141-7. DOI: 10.1177/2325957414554005
  38. 38. Olsen K, Danielsen K, Wilsgaard T, Sangvik M, Sollid JU, Thune I, et al. Obesity and Staphylococcus aureus nasal colonization among women and men in a general population. PLoS One 2013;8:e63716. DOI: 10.1371/journal.pone.0063716.
  39. 39. Nowak JE, Borkowska BA, Pawlowski BZ. Sex differences in the risk factors for Staphylococcus aureus throat carriage. Am J Infect Control 2017;45:29-33. DOI: 10.1016/j.ajic.2016.07.013
  40. 40. Immergluck LC, Jain S, Ray SM, Mayberry R, Satola S, Parker TC, et al. Risk of skin and soft tissue infections among children found to be Staphylococcus aureus MRSA USA300 carriers. West J Emerg Med 2017;18:201-12. DOI: 10.5811/westjem.2016.10.30483
  41. 41. Liu CM, Price LB, Hungate BA, Abraham AG, Larsen LA, Christensen K, et al. Staphylococcus aureus and the ecology of the nasal microbiome. Sci Adv 2015;1:e1400216. DOI: 10.1126/sciadv.1400216
  42. 42. Elie-Turenne MC, Fernandes H, Mediavilla JR, Rosenthal M, Mathema B, Singh A, et al. Prevalence and characteristics of Staphylococcus aureus colonization among healthcare professionals in an urban teaching hospital. Infect Control Hosp Epidemiol 2010;31:574-80. DOI: 10.1086/652525
  43. 43. Price JR, Cole K, Bexley A, Kostiou V, Eyre DW, Golubchik T, et al. Transmission of Staphylococcus aureus between health-care workers, the environment, and patients in an intensive care unit: a longitudinal cohort study based on whole-genome sequencing. Lancet Infect Dis 2017;17:207-14. DOI: 10.1016/S1473-3099(16)30413-3
  44. 44. Olsen K, Falch BM, Danielsen K, Johannessen M, Sollid JE, Thune I, et al. Staphylococcus aureus nasal carriage is associated with serum 25-hydroxyvitamin D levels, gender and smoking status. The Tromsø Staph and Skin Study. Eur J Clin Microbiol Infect Dis 2012;31:465-73. DOI: 10.1007/s10096-011-1331-x
  45. 45. Cole AL, Schmidt-Owens M, Beavis AC, Chong CF, Tarwater PM, Schaus J, et al. Cessation from smoking improves innate host defense and clearance of experimentally inoculated nasal Staphylococcus aureus. Infect Immun 2018;86:e00912-17. DOI: 10.1128/IAI.00912-17
  46. 46. Zanger P, Nurjadi D, Schleucher R, Scherbaum H, Wolz C, Kremsner PG, et al. Import and Spread of Panton-Valentine Leukocidin–Positive Staphylococcus aureus Through Nasal Carriage and Skin Infections in Travelers Returning From the Tropics and Subtropics. Clin Infect Dis 2012;54:483-92. DOI: 10.1093/cid/cir822
  47. 47. Roghmann MC, Johnson JK, Stine OC, Lydecker AD, Ryan KA, Mitchell BD, et al. Persistent Staphylococcus aureus colonization is not a strongly heritable trait in Amish families. PLoS One 2011;6: e17368. DOI: 10.1371/journal.pone.0017368
  48. 48. Andersen PS, Pedersen JK, Fode P, Skov RL, Fowler Jr VG, Stegger M, et al. Influence of host genetics and environment on nasal carriage of Staphylococcus aureus in Danish middle-aged and elderly twins. J Infect Dis 2012;206:1178-84. DOI: 10.1093/infdis/jis491
  49. 49. Sasegbon A, Hamdy S. The anatomy and physiology of normal and abnormal swallowing in oropharyngeal dysphagia. Neurogastroenterol Motil 2017;29:1-15 DOI: 10.1111/nmo.13100
  50. 50. Fossum C, Beltran C, Ma DJ, Foote RL. Biological Model for Predicting Toxicity in Patients With Head and Neck Cancer Treated With Proton Beam Therapy. Int J Radiat Oncol Biol Phys 2016;96:E616-E617.
  51. 51. de Steenhuijsen Piters WA, Sanders EA, Bogaert D. The role of the local microbial ecosystem in respiratory health and disease. Philos Trans R Soc Lond B Biol Sci 2015;370:20140294. DOI: 10.1098/rstb.2014.0294
  52. 52. Bignardi GE, S Lowes. "MRSA screening: throat swabs are better than nose swabs." J Hosp Infect 2009;71:373-4. DOI: 10.1016/j.jhin.2009.01.003
  53. 53. Lee CJ, Sankaran S, Mukherjee DV, Apa ZL, Hafer CA, Wright L, et al. Staphylococcus aureus oropharyngeal carriage in a prison population. Clin Infect Dis 2011;52:775-8. DOI: 10.1093/cid/cir026
  54. 54. Mertz D, Frei R, Jaussi B, Tietz A, Stebler C, Flückiger U, et al. Throat swabs are necessary to reliably detect carriers of Staphylococcus aureus. Clin Infect Dis 2007;45:475-7. DOI: 10.1086/520016
  55. 55. Nahimana I, Francioli P, Blanc DS. Evaluation of three chromogenic media (MRSA-ID, MRSA-Select and CHROMagar MRSA) and ORSAB for surveillance cultures of methicillin-resistant Staphylococcus aureus. Clin Microbiol Infect 2006;12:1168-74. DOI: 10.1111/j.1469-0691.2006.01534.x
  56. 56. Cirkovic I, Stepanovic S, Skov R, Trajkovic J, Grgurevic A, Larsen AR. Carriage and genetic diversity of methicillin-resistant Staphylococcus aureus among patients and healthcare workers in a Serbian university hospital. PLoS One 2015;10:e0127347. DOI: 10.1371/journal.pone.0127347
  57. 57. Tacconelli E, Foschi F. Does gender affect the outcome of community-acquired Staphylococcus aureus bacteraemia? Clin Microbiol Infect 2017;23:23-5. DOI: 10.1016/j.cmi.2016.09.011
  58. 58. Krismer B, Weidenmaier C, Zipperer A, Peschel A. The commensal lifestyle of Staphylococcus aureus and its interactions with the nasal microbiota. Nat Rev Microbiol 2017;15:675-87. DOI: 10.1038/nrmicro.2017.104
  59. 59. Wos-Oxley ML, Plumeier I, Von Eiff C, Taudien S, Platzer M, Vilchez-Vargas R, et al. A poke into the diversity and associations within human anterior nare microbial communities. ISME J 2010;4:839-51. DOI: 10.1038/ismej.2010.15
  60. 60. Yan M, Pamp SJ, Fukuyama J, Hwang PH, Cho DY, Holmes S, et al. Nasal microenvironments and interspecific interactions influence nasal microbiota complexity and S. aureus carriage. Cell Host Microbe 2013;14:631-40. DOI: 10.1016/j.chom.2013.11.005
  61. 61. Grice EA, Kong HH, Conlan S, Deming CB, Davis J, Young AC, et al. Topographical and temporal diversity of the human skin microbiome. Science 2009;324:1190-2. DOI: 10.1126/science.1171700
  62. 62. Huttenhower C, Gevers D, Knight R, Abubucker S, Badger JH, Chinwalla AT, et al. Structure, function and diversity of the healthy human microbiome. Nature 2012;486:207-14. DOI: 10.1038/nature11234
  63. 63. Segata N, Waldron L, Ballarini A, Narasimhan V, Jousson O, Huttenhower C. Metagenomic microbial community profiling using unique clade-specific marker genes. Nat Methods 2012;9:811-4. DOI: 10.1038/nmeth.2066
  64. 64. Kaspar U, Kriegeskorte A, Schubert T, Peters G, Rudack C, Pieper DH, et al. The culturome of the human nose habitats reveals individual bacterial fingerprint patterns. Environ Microbiol 2016;18:2130-42. DOI: 10.1111/1462-2920.12891
  65. 65. Mahdavinia M, Keshavarzian A, Tobin MC, Landay AL, Schleimer RP. A comprehensive review of the nasal microbiome in chronic rhinosinusitis (CRS). Clin Exp Allergy 2016;46: 21-41. DOI: 10.1111/cea.12666
  66. 66. Kumpitsch C, Koskinen K, Schöpf V, Moissl-Eichinger C. The microbiome of the upper respiratory tract in health and disease. BMC Biol 2019;17:87. DOI: 10.1186/s12915-019-0703-z
  67. 67. Biesbroek G, Tsivtsivadze E, Sanders EA, Montijn R, Veenhoven RH, Keijser BJ, et al. Early respiratory microbiota composition determines bacterial succession patterns and respiratory health in children. Am J Respir Crit Care Med 2014;190:1283-92. DOI: 10.1164/rccm.201407-1240OC
  68. 68. Peterson SW, Knox NC, Golding GR, Tyler SD, Tyler AD, Mabon P, et al. A study of the infant nasal microbiome development over the first year of life and in relation to their primary adult caregivers using cpn60 universal target (UT) as a phylogenetic marker. PLoS One 2016;11:e0152493. DOI: 10.1371/journal.pone.0152493
  69. 69. Lemon KP, Klepac-Ceraj V, Schiffer HK, Brodie EL, Lynch SV, Kolter, R. Comparative analyses of the bacterial microbiota of the human nostril and oropharynx. mBio 2010;1:e00129-10. DOI: 10.1128/mBio.00129-10
  70. 70. Camarinha-Silva A, Jáuregui R, Pieper DH, Wos-Oxley ML. The temporal dynamics of bacterial communities across human anterior nares. Environ Microbiol Rep 2012;4:126-32. DOI: 10.1111/j.1758-2229.2011.00313.x
  71. 71. Mirzaei MK, Maurice CF. Ménage à trois in the human gut: interactions between host, bacteria and phages. Nat Rev Microbiol 2017;15:397-408. DOI: 10.1038/nrmicro.2017.30
  72. 72. McCarthy AJ, Loeffler A, Witney AA, Gould KA, Lloyd DH, Lindsay JA. Extensive horizontal gene transfer during Staphylococcus aureus co-colonization in vivo. Genome Biol Evol 2014;6:2697-708. DOI: 10.1093/gbe/evu214
  73. 73. Krismer B, Liebeke M, Janek D, Nega M, Rautenberg M, Hornig G, et al. Nutrient limitation governs Staphylococcus aureus metabolism and niche adaptation in the human nose. PLoS Pathog 2014;10:e1003862. DOI: 10.1371/journal.ppat.1003862
  74. 74. Olson ME, Nygaard TK, Ackermann L, Watkins RL, Zurek OW, Pallister KB, et al. Staphylococcus aureus nuclease is an SaeRS-dependent virulence factor. Infect Immun 2013;81:1316-24. DOI: 10.1128/IAI.01242-12
  75. 75. Tomazic PV, Birner-Gruenberger R, Leitner A, Obrist B, Spoerk S, Lang-Loidolt D. Nasal mucus proteomic changes reflect altered immune responses and epithelial permeability in patients with allergic rhinitis. J Allergy Clin Immunol 2014;133:741-50. DOI: 10.1016/j.jaci.2013.09.040
  76. 76. Koziel J, Potempa J. Protease-armed bacteria in the skin. Cell Tissue Res 2013;351:325-37. DOI: 10.1007/s00441-012-1355-2
  77. 77. Arnison PG, Bibb MJ, Bierbaum G, Bowers AA, Bugni TS, Bulaj G, et al. Ribosomally synthesized and post-translationally modified peptide natural products: overview and recommendations for a universal nomenclature. Nat Prod Rep 2013;30:108-60. DOI: 10.1039/c2np20085f
  78. 78. Septimus EJ, Schweizer ML. Decolonization in prevention of health care-associated infections. Clin Microbiol Rev 2016; 29:201-22. DOI: 10.1128/CMR.00049-15
  79. 79. Janek D, Zipperer A, Kulik A, Krismer B, Peschel A. High frequency and diversity of antimicrobial activities produced by nasal Staphylococcus strains against bacterial competitors. PLoS Pathog 2016;12: e1005812. DOI: 10.1371/journal.ppat.1005812
  80. 80. Bierbaum G, Sahl HG. Lantibiotics: mode of action, biosynthesis and bioengineering. Curr Pharm Biotechnol 2009;10:2-18. DOI: 10.2174/138920109787048616
  81. 81. Donia MS, Cimermancic P, Schulze CJ, Brown LCW, Martin J, Mitreva M, et al. A systematic analysis of biosynthetic gene clusters in the human microbiome reveals a common family of antibiotics. Cell 2014;158:1402-14. DOI: 10.1016/j.cell.2014.08.032
  82. 82. Zipperer A, Konnerth MC, Laux C, Berscheid A, Janek D, Weidenmaier C, et al. Human commensals producing a novel antibiotic impair pathogen colonization. Nature 2016;535:511-6. DOI: 10.1038/nature18634
  83. 83. Nakatsuji T, Chen TH, Narala S, Chun KA, Two AM, Yun T, et al. Antimicrobials from human skin commensal bacteria protect against Staphylococcus aureus and are deficient in atopic dermatitis. Sci Transl Med 2017;9:eaah4680. DOI: 10.1126/scitranslmed.aah4680
  84. 84. Mądry A, Jendroszek A, Dubin G, Wladyka B. Production of Lysostaphin by Nonproprietary Method Utilizing a Promoter from Toxin–Antitoxin System. Mol Biotechnol 2019;61:774-82. DOI: 10.1007/s12033-019-00203-4
  85. 85. Selva L, Viana D, Regev-Yochay G, Trzcinski K, Corpa JM, Novick RP, et al. Killing niche competitors by remote-control bacteriophage induction. Proc Natl Acad Sci U S A 2009;106:1234-8. DOI: 10.1073/pnas.0809600106
  86. 86. Lijek RS, Luque SL, Liu Q , Parker D, Bae T, Weiser JN. Protection from the acquisition of Staphylococcus aureus nasal carriage by cross-reactive antibody to a pneumococcal dehydrogenase. Proc Natl Acad Sci U S A 2012;109:13823-8. DOI: 10.1073/pnas.1208075109
  87. 87. Uehara Y, Kikuchi K, Nakamura T, Nakama H, Agematsu K, Kawakami Y, et al. H2O2 produced by viridans group streptococci may contribute to inhibition of methicillin-resistant Staphylococcus aureus colonization of oral cavities in newborns. Clin Infect Dis 2001;32:1408-13. DOI: 10.1086/320179
  88. 88. Ahn J, Chen CY, Hayes RB. Oral microbiome and oral and gastrointestinal cancer risk. Cancer Causes Control 2012;23:399-404. DOI: 10.1007/s10552-011-9892-7
  89. 89. Gao Z, Kang Y, Yu J, Ren L. Human pharyngeal microbiome may play a protective role in respiratory tract infections. Genomics Proteomics Bioinformatics 2014;12:144-50. DOI: 10.1016/j.gpb.2014.06.001
  90. 90. Jordán F, Lauria M, Scotti M, Nguyen TP, Praveen P, Morine M, et al. Diversity of key players in the microbial ecosystems of the human body. Sci Rep 2015;5:15920. DOI: 10.1038/srep15920
  91. 91. Kim TH, Johnstone J, Loeb M. Vaccine herd effect. Scand J Infect Dis 2011;43:683-9. DOI: 10.3109/00365548.2011.582247
  92. 92. Quintero B, Araque M, Van Der Gaast-de Jongh C, Escalona F, Correa M, Morillo-Puente S, et al. Epidemiology of Streptococcus pneumoniae and Staphylococcus aureus colonization in healthy Venezuelan children. Eur J Clin Microbiol Infect Dis 2011;30:7-19. DOI: 10.1007/s10096-010-1044-6
  93. 93. Bogaert D, Keijser B, Huse S, Rossen J, Veenhoven R, Van Gils E, et al. Variability and diversity of nasopharyngeal microbiota in children: a metagenomic analysis. PloS One 2011;6:e17035. DOI: 10.1371/journal.pone.0017035

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Samuel González-García, Aída Hamdan-Partida, Anaíd Bustos-Hamdan and Jaime Bustos-Martínez

Submitted: 05 July 2020 Reviewed: 05 January 2021 Published: 22 January 2021