Salmonella enterica Transmission and Antimicrobial Resistance Dynamics across One-Health Sector

Abstract

From human infection to animal production and the environment, Salmonella enterica has become a global-threat. The pathogen’s dynamics have been determined by its transfer from sector to sector. Antibiotic-resistant bacteria can survive and proliferate in antibiotics. Misuse of antibiotics has made certain S. enterica resistant. The One-Health sector has antibiotic-resistant Salmonella (an approach that recognizes that human health is closely connected to the health of animals and the shared environment). According to certain studies, most animal and environmental S. enterica have virulence genes needed for human infections. S. enterica antibiotic resistance patterns have varied over the decades, resulting in pan-drug-resistant-strains. Plasmid-mediated fluoroquinolone resistance genes are found in One-Health Salmonella species. The S. enterica subspecies Typhi has been found to be extensively drug-resistant (XDR) in some areas. Cephalosporin-resistant S. enterica subspecies Typhi is a severe problem that underscores the need for Vi-conjugat-vaccines. New diagnostics for resistant-Salmonella in food, animal, environment, and human sectors are needed to control the spread of these deadly infections. Also, hygiene is essential as reduced transmissions have been recorded in developed countries due to improved hygienic practices. This chapter aims to discuss the transmission and antimicrobial resistance dynamics of S. enterica across the One-Health sector.

1. Introduction

Antibiotic-resistant Salmonella are pathogens that antibiotics cannot control or kill. They may survive and even increase in the presence of an antibiotic. Salmonella is the causative agent of salmonellosis, an intestinal illness affecting humans and animals [1]. Salmonellosis is a fairly prevalent disease that is transmitted around the world. Salmonella is a leading agent in the development of acute and chronic diarrhea. Some species have been linked to systemic infection and sepsis that led to the deaths of various animals and humans. Salmonellosis is significant in the One-Health strategy and is consequently of major relevance to public health [2]. Recently, resistant Salmonella has been found in humans, animals, and the environment (One-Health sector) [3]. One-Health sector is a concept used to recognize the interrelation of human health, animal health, and the shared environment and how diseases and pathogens move across the three sectors. Salmonella infection has been shown to produce severe systemic illness, which is responsible for large economic losses to the commercial chicken sector due to morbidity, mortality, and decreased egg production [4, 5] as reported by the Food and Agriculture Organization (FAO). The transmission has been a subject of argument by several writers [6, 7].

The selection pressure induced by antimicrobials Salmonella is a driving factor behind the emergence and spread of resistant bacteria, including Salmonella enterica pathogens, which were genetically encoded, transmitted by successive offspring, and in some instances could be transferred horizontally to distantly related bacteria [4]. Also, employing antimicrobials in food animal husbandry has increased the emergence of resistant S. enterica from food-producing animals [8]. Antibiotic-resistant Salmonella infections have grown in recent decades, making treatment more challenging. Because antimicrobial resistance is passed from one generation of bacteria through vertical transmission, resistant bacteria, in this case S. enterica, keep striving. Antibiotic-resistant Salmonella has risen for numerous causes. Salmonella infections require new antibacterial classes [9]. Some scientists hypothesize that Salmonella antimicrobial resistance is linked to invA expression and other mechanisms by which Gram-negative bacteria develop resistance [10, 11]. Some S. enterica subspecies Typhi strains with reduced ciprofloxacin sensitivity have emerged in the Indian subcontinent, southern Asia, and sub-Saharan Africa, leading to treatment failure [9, 12, 13]. S. enterica subspecies Typhi has resistant to first-line antibiotics such as chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole [13, 14]. Ceftriaxone, cefotaxime, and cefixime are also used to treat enteric fever, including nalidixic- and fluoroquinolone-resistant forms [10, 11].

Continuous abuse regarding the overuse of fluoroquinolone and certain cephalosporins in the management of Salmonella infection is underscored by the lack of effective antimicrobial stewardship programs, which has impacted antimicrobial resistance issues. Horizontal transfer of resistance genes via genetic elements like plasmids, transposons, and integrons has also impacted antimicrobial resistance issues, rendering those previously susceptible to becoming non-susceptible. Thus, the observed resistance or reduced susceptibility of Salmonellae to fluoroquinolones and some cephalosporins could result from genetic modification due to gene transfer. The resistant genes in Salmonella are embedded in the Salmonella pathogenic islands (SPIs). Studies have identified several SPIs, particularly the presence of mobile genetic elements (MGEs), which caused the rapid spread of resistant genes due to the high transmissible MCEs from one bacterium to the other [15, 16]. S. enterica are highly associated with multiple MGEs; these MGEs are in the SPIs, which are the center of virulence of S. enterica [17]. This book chapter aims to discuss the transmission dynamic of antibiotic-resistant S. enterica across humans, environments, and animals. The chapter discusses the genus Salmonella; the host adaptability of Salmonella; the virulence determinants of Salmonella; the transmission of antibiotic-resistant S. enterica in humans, animals, and the environment; and the detection of S. enterica and its antimicrobial resistance.

2. The genus Salmonella

Dr. Daniel Salmon, a veterinary bacteriologist who worked for the United States Department of Agriculture (USDA), was honored by having his name bestowed on the genus Salmonella [18]. Salmonella is non-sporulating short Gram-negative bacilli [19], and most move with the help of peritrichous flagella. However, some serotypes of Salmonella, such as Salmonella pullorum and Salmonella gallinarum, are not motile [20]. They may be aerobic or facultative anaerobic, and the optimal temperature range for growth is between 5 and 45 degrees Celsius. At a temperature of 37 degrees Celsius, growth is most optimal. The optimum pH for reproduction is 7; however, Salmonella may live in environments with pH values ranging from 4 to 9 [21]. They grow in culture media designed for enterobacteriaceae and in blood agar. In addition, they grow in specialized media such as Salmonella-Shigella Agar and some ChromoAgar. Their colonies range from 2 to 4 millimeters in diameter and have smooth and round edges. They are slightly raised in a medium that contains carbon and nitrogen [22, 23]. When preserved in variable media such as peptone broth, colonies have the potential to maintain their viability for a significant amount of time [23, 24]. Salmonella strains have the biochemical capacity to catabolize nutrients, D-glucose, and other carbohydrates, except for lactose and sucrose, resulting in the generation of acid and gas [25]. Salmonella can utilize citrate as their only source of carbon, reduce nitrate to nitrite, and have the potential to produce hydrogen sulfide [19]. They are catalase positive and oxidase negative. They neither ferment malonate nor hydrolyze urea, and they do not produce indole. The bacterium has a coating of mucus around it, which helps to protect it from being digested by phagocytes, and it also has a fringe of fimbria placed around its outer surface, which helps it adhere to cells [19, 25, 26].

Salmonella is a member of the family of bacteria known as Enterobacteriaceae, which, along with other major pathogens in this group, are frequently implicated in causing illness in the small intestine. However, once the bacteria establish a foothold in the small intestine, they can move throughout the body and cause full-blown systemic disease [25]. S. enterica and Salmonella bongori are the two taxonomic species that make up the genus Salmonella. There are six subspecies of S. enterica: S. enterica subspecies enterica, S. enterica subspecies salamae (II), S. enterica subspecies arizonae (IIIa), S. enterica subspecies diarizonae (IIIb), S. enterica subspecies houtenae (IV), and S. enterica subspecies indica (VI) [25]. S. bongori and most of the subspecies of S. enterica populate the environments of cold-blooded animals, and in certain instances, S. enterica may cause sickness in these animals [27]. However, S. enterica subspecies enterica is the most biomedically significant subspecies. This is because these subspecies’ serovars have a particularly important clinical importance in both veterinary and human disorders. Based on the structures of their flagellar (H) antigens and lipopolysaccharide (LPS) (O) antigens, S. enterica subspecies enterica may be further subdivided into approximately 2500 different serovars [25, 28].

2.1 Host adaptability of S. enterica

Despite their genetic connection, Salmonella strains may be distinguished from one another by their virulence, host adaptability, and host specificity [24, 25]. There is a wealth of epidemiologic information about S. enterica subspecies serovar host specificity. Certain serovars have a preference for certain hosts but are not exclusive to those hosts. Serovars Typhi, Paratyphi A, Gallinarum, and Pullorum are only transmitted from one host to another. Serovar Typhi is responsible for causing typhoid fever in humans [13, 29], while serovar Paratyphi A causes paratyphoid in humans [30]. The serovar Pullorum is responsible for causing disease in poultry, known as systemic pullorum disease [31, 32, 33], which is associated with high mortality and intestinal inflammation [34]. In contrast, serovar Gallinarum is responsible for causing severe systemic fowl [35, 36].

Both Salmonella typhimurium and Salmonella enteritidis can infect a wide variety of animal hosts. Interestingly, they are responsible for transmitting distinct illnesses in various animal species [3, 33, 34, 35]. In humans, the serovar Dublin is sometimes known to induce septicemia and gastrointestinal illness [32, 33]. The serovar Typhimurium and, less often, Enteritidis may cause enterocolitis in calves, which can lead to death from dehydration [37]. The serovars Enteritidis and Typhimurium that cause systemic illness and diarrhea in freshly born chicks are carried by older hens, who are asymptomatic carriers [4, 38]. Serovars Enteritidis and Typhimurium induce a localized, self-limiting form of enterocolitis in humans with healthy immune systems. However, immunocompromised people are more likely to develop a systemic form of the illness [29, 39]. In mouse strains that are sensitive to the illness, serovars Enteritidis and Typhimurium may induce a systemic fever similar to typhoid, although, in other investigations, they do not cause diarrhea [36, 40, 41].

2.2 Virulence determinants of Salmonella

Salmonella displays a wide range of virulence factors that make the bacterium harmful [9, 42]. Polymorphic surface carbohydrates, an abundance of fimbrial adhesins, phase-variable flagella, and well-structured invasion and survival mechanisms in host macrophages and other cells are likely examples of these traits [43, 44]. Nearly 200 genes on the chromosomes of Salmonella are crucial for the pathogenicity of the bacterium [36]. These genes are located in the five SPI-1 to SPI-5 chromosomal pathogenicity islands. A genetic component called a pathogenicity island may also be found on the chromosome [45]. This part of the chromosome exists as a separate and distinct entity from the rest of it. All pathogenicity islands have a few traits, including the inability to be identified in closely related, nonpathogenic reference species or strains and the frequent encapsulation of substantial areas of DNA (10–200 kB), containing genes that typically impart virulence to bacteria [46, 47, 48, 49, 50, 51].

In most cases, they are also connected to elements like inverted repeats, transposases, and integrases [52]. Two of the type III secretion systems that allow Salmonella species to colonize new environments more easily are encoded by SPI-1 and SPI-2 [53]. Salmonella SPI-2 is only found in Salmonella species and is conserved across all of these species [43]. Even though SPI-2 is the sole gene unique to Salmonella, SPI-2 is necessary to establish bacterial invasion and internalization. At the same time, SPI-1 is necessary for developing systemic infection and intracellular replication [54, 55, 56, 57]. The SPI-1 protein is necessary for bacterial invasion and internalization [58]. Therefore, an SPI1 gene that is both present and functioning is required for Salmonella species to be able to cause sickness [58]. On centisome 63 of Salmonella pathogenicity island-1, a 40 kb region carries a significant portion of the genes required for intestinal penetration and invasion of host cells [58]. The Salmonella pathogenicity island-1 includes this region [59]. Environmental isolates of Salmonella that had naturally occurring deletions in the SPI-1 region were unable to enter mammalian cells, according to research by Ginocchio and associates [60]. Salmonella isolates have the potential to colonize and infiltrate intestinal epithelial cells as well as transfer pathogenic effector proteins from the bacteria into the cytosol of the host cell due to the presence of at least 37 genes in the SPI-1. Salmonella isolates may also transfer harmful effector proteins into the host cell’s cytoplasm. Numerous parts of the type III secretion systems (T3SSs) [61], as well as their regulators and secreted effectors, are encoded by these genes [62]. SPI-1 is included inside the Salmonella pathogenicity island 1. After invaders seize control of host cells, the SPI-2 genes express themselves. These genes, which are required for intracellular life, are only present in Salmonella for survival within epithelial cells and macrophages [63]. Mutants’ pathogenicity was much diminished because they could not colonize the infected individuals’ spleens and lacked SPI-2 genes [58, 63]. The effector proteins sipA, sipB, sipC, sifA, hilA, hilC, and hilD, as well as invA, spiC, and invF, are among those secreted [61]. These chromosomal clusters of virulence genes can only be found in Salmonella and are unique to those species.

2.3 Transmission of antibiotic-resistant S. enterica in humans, animals, and the environment

Antibiotic resistance mechanisms in S. enterica include resistance to aminoglycosides (e.g., alleles of aacC, aadA, aadB, ant, aphA, and StrAB), B-lactams (e.g., blaCMY-2, TEM-1, and PSE-1), chloramphenicol (e.g., floR, cmlA, and StrAB), and other antibiotics [64]. In some strains of Salmonella, multidrug resistance mechanisms were shown to be associated with integrons or mobile genetic elements (MGEs) such as IncA/C plasmids [65, 66]. Salmonella that is resistant to antibiotics may be transmitted from animals raised for food to people; in this case, there will be similarities in the resistant patterns and genes present [67]. Salmonella strains that are resistant to antibiotics have been found in humans, and some of these strains have antibiotic-resistant components that are the same as those found in Salmonella isolated from food animals [5, 68, 69]. This suggests that these strains may have come from the same source, which is an evidence of cross-transmission.

Humans are the principal reservoir for Salmonella serovars Typhi and other human-specific serovars. In contrast, other animal species are the key reservoirs for non-typhoidal Salmonella (NTS), which has been linked to human illnesses and infections in other animal species [13]. Salmonella may be found in the feces of practically every animal species; as a result, the zoonotic transmission of Salmonella is not restricted to animals raised for human consumption alone [70, 71]. Foods produced from poultry are the primary cause of Salmonella infections in humans, namely, in eggs, egg products, and chicken meat. Veterinarians and public health officials have identified the shedding of Salmonella as a source of infections for dog handlers, dog owners, and the communities in which they live [18, 22]. This suggests that pets, and particularly dogs in close contact with humans, may be responsible for the transmission of Salmonella. Infected dogs may continue to be carriers of the disease and feces shedders, making them a source of Salmonella for humans and other animals. Although these sources are not often responsible for big outbreaks, they may be responsible for isolated occurrences [70], which is why contact with ill cattle is a systematic way for farm workers to be exposed to diseases. The Centers for Disease Control and Prevention (CDC) reported several outbreaks of multidrug-resistant S. typhimurium infection associated with veterinary facilities. In areas with poor sanitation and contaminated water, fecal–oral transmission from person to person is the route for enteric or typhoid fever [71]. Salmonella typhi is only known to be carried by humans, not any other animals. S. enterica serovars, which have a wide host range, are common in the populations of warm-blooded animals that contribute to the human food supply.

Bacterial transmission typically occurs through the consumption of raw or undercooked food products [63], with poultry being one of the most important reservoirs of Salmonella species [13, 37]. Salmonella strains of many different serotypes have been identified from their natural environments and food sources around the globe [29, 72]. According to Fazl and colleagues’ research [45], hens are the primary vector for the vertical spread of Salmonella, which occurs via the ingestion of chicken eggs. Salmonella spreads quickly from breeding flocks to broiler and commercial egg-laying flocks. Salmonella spreads horizontally between birds through the fecal–oral pathway. The bacteria persist in the environment and have been isolated from poultry litter and dust [73]. The CDC reported in August 2018 about an outbreak of Salmonella Infantis from chicken products, which had also been reported previously [71, 74, 75].

Animal diseases are often brought on by ingesting contaminated food or water. To infiltrate the intestinal epithelium and colonize the mesenteric lymph nodes and other internal organs in the case of a systemic infection. Salmonella bacteria must withstand the challenging circumstances of the digestive tract [67]. Both humans and animals may get Salmonella infections when exposed. The ability of Salmonella to link with host cells and trigger its internalization has been studied [13]. These are essential for Salmonella to survive in the host environment and enter non-phagocytic cells. Animal waste commonly allows Salmonella to enter agricultural environments [76]. Plants and surface water used for irrigation or as a diluent for pesticides or fertilizers may be directly contaminated by animal feces [77]. There has been an increase in recent years in the number of reports that show a link between foodborne disease and the eating of fresh produce contaminated with Salmonella [78]. Salmonella can adapt to various environmental conditions, including those with a low pH or high temperature, allowing it to survive outside the host organism. Salmonella may adhere to plant surfaces and attach before actively infecting a variety of plant interiors. Salmonella that originates in plants retains its virulence when infecting animals [79]. Plants may thus act as a secondary host for Salmonella infections and contribute to spreading the bacteria to animals and humans.

2.4 Antimicrobial resistance of S. enterica from humans, animals, and the environment

The mechanisms of antibiotic resistance fall into three categories: (1) inactivation of the antimicrobial, (2) efflux or changes in permeability or transport of the resistance pathogen, or (3) modification or replacement of the antimicrobial target [80, 81]. Resistance is genetically encoded and may result from mutations in endogenous genes, horizontal gene transfer via plasmids, or horizontal acquisition of alien resistance genes [81, 82]. Both horizontally acquired genes and point mutations may contribute to resistance encoding. Promoter or operator point mutations might be the root cause of overexpression of endogenous genes like the AmpC-lactamase gene or the mar locus [83]. Some antimicrobial target genes, like the gyrase gene, are susceptible to point mutations that may turn them into resistant targets. Exogenous resistance genes encoded on plasmids, integrons, phage, and transposons can be horizontally propagated via the processes of transformation, conjugation, and transduction [84]. This includes genes that code for enzymes that render the antimicrobial inactive, such as lactamases that cleave the four-membered ring in lactams; efflux systems, such as tet (A); altered versions of the enzymes the antimicrobial is intended to inhibit, such as dfrA; or enzymes that alter the antimicrobial target, such as ribosomal RNA methylase [85, 86, 87].

Additionally, by researching the mechanisms of resistance, one may discover the genetic link between animal and human resistance [88, 89]. Suppose the antibiotic resistances seen in human bacterial isolates are closely related to those seen in animal isolates. In that case, it may be possible to identify animal sources of resistant bacteria in human infections that can be targeted to reduce human disease [76, 90, 91]. This can be done by determining if the resistances seen in human bacterial isolates are similar to those seen in animal isolates [92]. This is possible due to the diversity of genetic factors contributing to antibiotic resistance.

Antibiotic resistance among Salmonella strains is increasing, which is a major cause for worry in protecting public health worldwide [93]. At the beginning of the 1960s, it was revealed that Salmonella had first developed resistance to a single antibiotic [88]. Since then, more Salmonella strains resistant to one or more antimicrobial medications have been isolated in various countries, including developed nations [94]. This trend has been seen in several countries. Traditional antibiotic therapies for Salmonella infections include penicillin, chloramphenicol, and trimethoprim-sulfamethoxazole, which are just a few available options. These treatments are believed to be the earliest lines of defense against Salmonella. Salmonella strains resistant to many antibiotics are referred to as multidrug-resistant Salmonella. The MDR phenotypic characteristic was extensively dispersed throughout S. enterica over an extended time, particularly in S. typhi and, to a lesser degree, in Salmonella paratyphi [68, 95]. Asia and Africa are two continents with a substantial incidence of S. enterica strains with the MDR feature [96]. During a surveillance investigation carried out in several nations in Asia and Africa, a significant number of S. enterica MDR isolates were identified [97]. The research particularly pointed to Pakistan, India, Nepal, and Vietnam, where extensive drug-resistant Salmonella was discovered. Because of the widespread use of fluoroquinolones and extended-spectrum cephalosporins, which were used to treat MDR S. enterica, there has been an increase in S. enterica that are capable of producing beta-lactamases [17, 98]. This is because traditional antibiotics have become less effective due to the widespread use of drugs like fluoroquinolones and extended-spectrum cephalosporins. Despite this, some evidence suggests that an increasing number of typhoid Salmonella are acquiring resistance to fluoroquinolones. Isolates from various nations have been reported to be resistant to nalidixic acid, which suggests that they have diminished sensitivity to ciprofloxacin and other fluoroquinolones [93, 99]. The rise in resistant non-typhoidal Salmonella (NTS), particularly in animals used in food production, has made controlling the spread of S. enterica strains resistant to antibiotics more difficult. This is true in particular for animals that are reared for their meat. According to the investigation findings, the MDR phenotype was present in most NTS clinical isolates. Public health officers have voiced their worries over treating ailment and prevention due to this phenomenon.

The use of antibiotics in animal feed to stimulate the development of food animals and in veterinary care to treat bacterial illnesses in those animals is the primary factor that contributes to the establishment of Salmonella with antimicrobial resistance [67]. This is a high risk of zoonotic illness due to the transfer of MDR Salmonella strains from animals to people via the intake of food or water contaminated with the feces of the animals, through direct contact or by the consumption of diseased food animals. Additionally, multidrug-resistant Salmonella strains were discovered in the aquatic habitat of some exotic pet animals, such as tortoises and turtles [100]. This might lead to an increased risk of zoonotic infections in people via direct contact with these animals [74, 76, 90].

2.5 Detection of S. enterica and its antimicrobial resistance

Several methods are used to detect Salmonella and its resistance patterns and genes. There are conventional or culture, serological, and molecular techniques, including polymerase chain reaction and sequencing. Confirming infection with Salmonella is required before treatment [101, 102, 103]. A diagnosis may be confirmed by culture and isolation. Salmonella isolates may be differentiated in various ways, and the number of Salmonella species is continually expanding [104, 105]. Salmonella is typed using complex procedures in addition to serotyping based on antigens to track individual isolates and explain pathogenicity [58, 86]. It is essential from an epidemiological standpoint to distinguish Salmonella isolates because definitive typing may assist in locating the source of an epidemic and tracking changes in antibiotic resistance [105].

Pre-enrichment, selective enrichment and culturing, isolation, biochemical characterization, serological characterization, and final identification are the steps that are included in the standard approach for detecting Salmonella [106, 107]. This method needs at least 4 days to get a negative result, and it takes between six and 7 days to identify and confirm positive samples.

Antibiotic sensitivity testing (AST) measured by inhibition zones is determined by the disk diffusion method, and it is proportional to the susceptibility of the bacteria to the antibiotic on the disk [108]. This depends on the antibiotic disk’s potency and infusing ability. It may not take much modification to use disk diffusion for testing antimicrobial disks [109]. It is used to screen many isolates to choose a subset for further testing, such as MIC determinations. Antimicrobial types must include interpretation criteria (susceptible, intermediate, and resistant) based on standards, guidelines, and quality control reference organisms. Approaches to AST are selected based on their user-friendliness, versatility, adaptability to automated or semi-automated systems, cost-effectiveness, dependability, and accuracy. Conventional Salmonella serotyping is most typically done [110].

S. enterica serotyping is conducted on a global scale, which has enabled improvements in the monitoring and detection outbreaks on a global scale. The O (somatic), H (flagellar), and Vi (capsular) antigens from the lipopolysaccharide (LPS) layer of the cell wall are used for serotyping Salmonella isolates [111, 112]. Salmonella may spontaneously and reversibly change between these two stages of flagellar antigen synthesis, each containing a unique set of H antigens. This phenomenon is known as diphasic flagellar antigen production. In the first phase, also known as the specific phase, the various antigens are denoted by lowercase letters; in the second phase, also known as the group phase, the antigens found initially are given numbers [113, 114]. Traditional serotyping, which uses the autoagglutination method, has some important drawbacks. One is the inability to identify non-typeable Vi antigens and strains [75, 115]. It takes a lot of time, a lot of different chemicals, and a lot of experienced laboratory workers to do this [4].

Latex agglutination, enzyme immunoassay (EIA), and enzyme-linked immunosorbent assay (ELISA) are three examples of the types of immunological tests that have been developed to identify and confirm Salmonella [29, 39, 98] quickly.

DNA hybridization and PCR are two more methods that may be used to identify S. enterica [116, 117]. Amplification and analysis of strain variation may be accomplished by using gene-specific primers in PCR testing. It can improve the detection and characterization of pathogenic bacteria by targeting species-specific DNA regions and specific pathogenicity traits, such as genes that code for toxins, virulence factors, or major antigens [84, 118, 119]. This makes it possible for it to improve the detection of pathogenic bacteria. Other Salmonella strain typing methods include utilizing antibiotic resistance genes as epidemiological markers using multilocus sequence typing [5, 7, 111].

These methods examine the DNA sequences of a series of housekeeping, ribosomal, and virulent genes, and therefore making isolates distinction based on the molecular analysis. This uses short sequence repeat motifs as a target to type isolates.

The polymerase chain reaction (PCR) and real-time PCR are being investigated as potential diagnostic tools for enteric fever [112]. In theory, nucleic acid amplification tests (NAATs) might amplify DNA from bacteria that are either dead or incapable of being cultured, hence rectifying low culture positives caused by antibiotic pre-treatment [113]. According to research [114], the test sensitivity limitations for a PCR technique are the same as those for a culture approach. Culture and PCR are combined in some methodologies. The adoption of NAATs in developing countries is expected to be hampered because of the high cost and lack of laboratory infrastructure [120]. The effectiveness of NAATs for the diagnosis of enteric fever has been the subject of some research. The flagellin genes (fliC-d for S. Typhi and fliC-a for S. Paratyphi A) are most often targeted by PCR [121, 122]. In a study of blood PCR testing for enteric fever, researchers found that although all tests were 100 percent specific, their sensitivities differed [83, 123]. The sensitivity is considerable in most studies to be more than 90% [20] in persons with positive blood culture, but it is lower (3–13%) in those without clinical symptoms [14].

Additionally, PCR tests focusing on fliC have been applied to urine, and the findings have been favorable [124]. The primary benefit of PCR over other identification methods, like culture and conventional methods, is that it produces findings much more quickly [124]. PCR requires specialist laboratory equipment, which might be difficult in regions where typhoid fever is prevalent [14, 39]. Whole-genome sequencing (WGS) has revolutionized how antimicrobial resistance is studied [125, 126]. It has enabled the detection of resistance genes even before they are expressed and has also played a very important role in epidemiological studies of antimicrobial resistance Salmonella [127]. These techniques have helped develop newer diagnostics and are being explored in vaccine candidate development for several Salmonella species other than Typhi [128].

Both phenotypic and genotypic methods detect resistance genes or resistance mechanisms in bacteria, specifically in S. enterica [17]. The phenotypic method explores this bacteria’s expression of certain traits to detect a resistance mechanism [122]. For example, the resistance by Salmonella to third-generation cephalosporin is an indication of possible possession of extended-spectrum beta-lactamases (ESBLs) [129]. Salmonella resistance to Meropenem is an indication to been carbapenemase-producing [130]. Genotypic techniques are employed to confirm the phenotypic detection of an antibiotic-resistance mechanism [131]. Some of these genotypic methods for antibiotic resistance genes include whole genome sequencing and polymerase chain reaction application. Whole genome sequencing is expensive, and as such, it is not routinely used to detect resistance genes. Polymerase chain reaction (PCR) is the method of choice for laboratories with the capacity [132]. Quantitative and conventional PCR is used. Quantitative PCR uses specific primers and probes to detect the resistance or virulence gene of interest. Conventional PCR, which is mostly available and more cost-effective, uses specific primers, and the products are visualized in a gel documentation system after amplification [133].

2.6 Prevention and control of resistant antibiotics and virulent S. enterica across one-health sectors

The prevention of S. enterica infection involves proper co-ordination of preventive measures across the humans and their activities, that is, agriculture, animal rearing for food, the use of animals as companions or pets, and management of environment sector to detect and eliminate any threat [100, 134] of Salmonella [100, 134]. The different levels of prevention of S. enterica pathogens include: prevention of S. enterica pathogens from farms to human via food or through the contaminated environment via poor waste management [120, 135]. The proper management of farms to eliminate pathogenic bacteria from the animal facilities is one effective way of managing Salmonella outbreaks. Also, prosper handling of food processing and animal products contributed to reduced outbreaks [10, 136]. Some keys Salmonella infection outbreaks were associated with transmission from processed food animals like chickens, pork, and other meat products. The use of animal wastes as fertilizers has also been associated with S. enterica outbreaks [76]. Full implementation of good hygiene practices across all sectors, including house hygiene practices and deployment of WASH in all sectors, will eliminate S. enterica from the food chain and all possible transmission avenues.

By consuming contaminated food or drink, enteric fever is most often spread from person to person [134]. In the past, enteric fever was common in Western Europe and the United States [75]. Despite this, pasteurization of milk and other dairy products, the removal of human feces in the food-manufacturing process, and good food and water cleanliness have all contributed to a considerable decline in the prevalence of Salmonella infection [137]. There was a decrease in the number of Salmonella illnesses reported in Latin America simultaneously as sanitary techniques were implemented [137]. Giving access to clean water and food, maintaining proper sanitation, and administering typhoid vaccinations are the best ways to avoid enteric fever. Making and ensuring that water meant for human consumption is safe is the main goal of eliminating possible vectors for the transmission of typhoid Salmonella and non-typhoid Salmonella (NTS). This important objective has been easily achieved in wealthy nations like Europe and the United States but not in developing or underdeveloped countries [138]. In addition to water, a variety of foods may include Salmonella species. However, they are often found in poultry, eggs, and dairy products [139]. The adoption of proper food handling and cooking practices has been proposed to prevent bacterial contamination of food. Due to its efficacy in reducing the risk of food contamination, food irradiation has attracted considerable interest and support in several countries. Several public health agencies, including the WHO and the CDC, have approved irradiating food. Still, due to the risk posed by radioactivity, it is only partially used in certain parts of Europe and the United States [103]. Vaccination is one of the best methods to protect against enteric fever [140]. The inactive parenteral and oral live attenuated vaccines are the two immunization types that may presently be utilized to prevent enteric fever. However, these authorized immunizations are exclusively used in infants and are ineffective at preventing diseases by S. enterica subspecies Paratyphi and NTS. Limiting the erroneous use of antibiotics in food animals and the feed they ingest is one approach that is good for NTS.

Hazard analysis and critical control points (HACCP) are advantageous since it is an efficient strategy for minimizing risk and maximizing product security [141]. The HACCP is employed at various stages of the One-Health sector. This is important to avoid cross-contamination or transfer of pathogenic S. enterica from the environment to processed food, humans, and vice versa. One way of implementing HACCP in the animal sector is to ensure that Salmonella pathogens are not released into the environment [142]. And everyone involved in the processing steps of food are tested for S. enterica to avoid shedding in processed food [143]. Implementing HACCP has several advantages, including eliminating prejudice and providing a framework for prioritizing choices. HACCP helps ensure that only those with the necessary knowledge, skills, and experience are responsible for food safety. With HACCP in place, there is concrete proof of your food safety management, which will be useful in court in the case of any litigation. After the initial investment in implementing HACCP, the system may be very cost-efficient. As a result of HACCP, food manufacturers may fulfill their mandated duty to create healthy, wholesome fares in compliance with applicable regulations [144]. Applying HACCP’s procedures and guidelines almost guarantees better results every time. This is mostly attributable to people’s heightened sensitivity to risks and the fact that they come from all walks of the operation. The HACCP principles and the requisite support mechanisms for a robust food safety program form the basis of the Global Food Safety Initiative (GFSI) by ensuring the absence of Salmonella pathogens in processed food, poultry farms, and the food chain [142, 145].

3. Conclusion

The distribution of Salmonella subspecies capable of causing infections has been found in humans, animals, and environments. Salmonella genes such as sipA, sipB, sipC, sifA, hilA, hilC, hilD, as well as invA, spiC, and invF have been linked to epidemiologic of virulent S. enterica. Some of the Salmonella from all these sources tested positive for the beta-lactamase TEM enzyme. To detect S. enterica, invA has been found valuable in detecting S. enterica contamination in food products and the environment. The invA gene has been made into devices and diagnostics for diagnosing infections in the bloodstream, environmental contamination, and water-processing plants. These factors have also been utilized in investigating outbreaks and infection tracing and tracking, especially in food-processing industries. The detection of this genes even without viable growth of S. enterica has helped control and contain outbreaks. Genes for resistance to fluoroquinolones mediated by plasmids has also been widely found in Salmonella species across the One-Health sector. According to research findings, most Salmonellae are obtained from animals, and the environment carries the virulence genes essential to induce infections in humans. Extensively drug-resistant (XDR) Salmonella typhi is now a serious problem in some countries, multidrug-resistant (MDR) has grown in prevalence, and S. enterica has evolved resistance to an increasing number of antibiotic classes. Extensively drug-resistant (XDR) S. typhi, so designated due to its exhibited resistance to the recommended drugs for typhoid fever, including third-generation cephalosporin, has become a serious issue that highlights the urgency in deploying the Vi-conjugate vaccines.

Conflict of interest

The authors declare no conflict of interest.