Abstract
Staphylococcus aureus is an opportunistic pathogen and is frequently associated with the antimicrobial resistance. There has been horizontal gene transfer of Staphylococcus chromosome cassette mec (SCCmec) among the staphylococcal species that colonize a similar colonization niche, which eventually results in emergence of new variant with enhanced survival ability in terms of antimicrobial resistance and virulence level in S. aureus. Evolution and dissemination of SCCmec structure resulted in the emergence of methicillin-resistant S. aureus (MRSA) clones around the world covering hospital, community, and livestock settings. MRSA also has the ability to resist different antibiotic profiles known as multidrug-resistant S. aureus (MDR S. aureus).
Keywords
- Staphylococcus aureus
- SCCmec
- MRSA clones
- multi-drug-resistant S. aureus
1. Introduction
Methicillin-resistant
Multidrug-resistant MRSAs have also been reported that make the antibiotic regiment limited. Prevalence of MRSA is of a growing concern, particularly due to the more recent increased frequency of community-associated MRSA (CA-MRSA) and livestock-associated MRSA (LA-MRSA). Thus, this pathogen becomes a major concern in public health as well as livestock industry [10–13].
Many studies have been looking at the mechanism and dissemination pattern of MRSA and its genetic characteristics, but due to the potential, geographical, and temporal differences, a comprehensive review is needed to put the whole picture connected.
2. Staphylococcus aureus
The production of golden pigmentation of
Generally, 20–30% of individuals are persistent carriers of
Immunocompromised patients with
3. Methicillin-resistant S. aureus (MRSA)
MRSA has the ability to resist almost all available β-lactam antibiotics. Statistics showed about 40–70% of
Generally, MRSA can be categorized into two major groups known as hospital-associated MRSA (HA-MRSA) and community-associated MRSA (CA-MRSA). Globally, the majority of MRSA infections are HA-MRSA that are acquired from healthcare facilities. Currently, MRSA isolates are subdivided into three major groups known as hospital-associated MRSA (HA-MRSA), community-associated MRSA (CA-MRSA), and livestock-associated MRSA (LA-MRSA). Previous reports revealed that both HA-MRSA and CA-MRSA isolates differ distinctly from each other, with HA-MRSA showing high antimicrobial resistance but less virulence and lack of capabilities as colonizers [23–26]. Meanwhile, CA-MRSA isolates exhibit a low antimicrobial resistance but a high virulence harboring PVL gene and numerous pathogenicity factors, as well as good colonizers [26–29].
MRSA spread in population since 1990 and become the major cause of community-associated infection [27]. The scenario worsens when multidrug MRSA emerges, in which it can resist more than two antibiotics of different classes that reduce the option for available treatment of Staphylococcal infection [30, 31].
Methicillin resistance characteristic in
4. SCCmec structure
Staphylococcal cassette chromosome
A single SCC
4.1. Complete SCCmec
To date, the International Working Group-SCC
Furthermore, many different SCC
Different types of SCC
4.2. Pseudo-SCCmec
Pseudo-SCC
However, certain pseudo-SCC
ACME is found in both MRSA and MSSA, especially with sequence type ST8 (ST8), and has been disseminated in virulent
5. Origin of SCCmec structure
The origin of SCC
Several studies described coagulase-negative staphylococci (CoNS) as the primary reservoir of the SCC
5.1. From coagulase-negative staphylococci species to MRSA
The existence of various forms of SCC
5.2. From MSSA to MRSA
MRSA emerges when MSSA receives SCC
Wong et al. [64] identified SCC
6. Clonal dissemination of MRSA
Nowadays, the dissemination of MRSA has become a major global problem that threatens human health [27]. However, only limited clones of MRSAs could be inferred to disseminate in different countries and continents through genotypic analysis using several DNA typing methods such as SCC
MRSA strain COL was the first MRSA clone detected carrying SCC
The popular human MRSA pandemic clones, the EMRSA-15 and EMRSA-16, were identified in the United Kingdom (UK) around early 1990s. Since then, the clones become predominant healthcare-associated MRSA in UK [78, 79] and several European countries such as Denmark [80], Sweden [81], Belgium [79], and Spain [82]. Studies in Kuwait [83] and USA [84] also reported the spread of EMRSA-15 and 16 clones in hospital setting in the countries. To date, these clones have already been widespread in 15 countries around the world [85]. Both MRSAs belong to SCC
CA-MRSA clones have also been observed to disseminate worldwide particularly with sequence types ST80 and ST30. MRSA clone with ST80 is the most common CA-MRSA clone in European countries and usually carries PVL genes. Moreover, ST80 clone also showed resistance toward fluoroquinolones, tetracyclines, and fusidic acid [87]. CA-MRSA clone with sequence type ST30 was observed to disseminate in Asian and Oceanic countries. An example is the multidrug USA300 clone, known as West Pacific clone. It was first identified in the USA and carried plasmid that encodes several antibiotic resistance genes [88]. Enany et al. identified novel clones with sequence types ST1010 (121)c and ST1009 (1153)c isolated from Egypt after they analyzed different genetic patterns of PVL+CA-MRSA isolates from different countries [89].
In certain countries, it was found that MRSA can also spread among livestock, known as LA-MRSA. LA-MRSA CC398 is the popular clonal complex among livestock and has already been reported to spread in several European farms in Netherland, Denmark, Germany, France, and Italy [90]. MRSA CC398 was originated from pigs and spread among dairy cattle and turkey [91, 92]. In Netherlands, MRSA contamination on meat was reported after 2217 meat samples were analyzed covering 35.3% turkey, 15.2% beef, 15.2% veal, 10.7% pork, and 6.2% lamb meat [93]. LA-MRSA can be transmitted to human by physical contact with livestock contaminated with MRSA [94]. LA-MRSA may have equal virulence ability as compared to CA-MRSA and HA-MRSA toward human. Therefore, persons with continuous exposure to livestock carrying LA-MRSA are at high risk [95]. Other than meat, LA-MRSA can also be found in dairy milk. Recently, 11 sequence types were detected from LA-MRSA isolated from 15 Brazilian dairy farms (n = 552) with four of them contain novel sequence types (ST1622, ST1623, ST1624, and ST1625) [96].
7. Multidrug-resistant (MDR) MRSA
Antibiotic or antimicrobial drugs are the most effective therapeutic agents used in treating microbial infections through either one or both bactericidal and bacteriostatic effects. Nevertheless, antibiotic or antimicrobial drug resistance has been a major problem worldwide, with incidence of MRSA reported in healthcare facilities in Asia to reach its peak in late 1990s, and stayed at plateau level during 2000s [97]. The heavy usage of drugs in treatment hastens the selection of bacteria that harbor multidrug resistance genes particularly
The emergence of multidrug-resistant
There has been a dramatic increase in the incidence of nosocomial infections as well as community-associated MRSA and livestock-associated MRSA caused by strains of
Several studies attempted to profile all possible multidrug-resistant MRSA since 1987, encompassing samples from hospitals, community, as well as veterinary settings [113, 114]. Lim et al. (2013) carried out temporal comparative surveillance of antibiograms from clinical samples in 2003–2008 and showed a significant increase in resistance rates (from 1 to 96%), as well as multidrug-resistant phenotypes (96%). This study also indicated the prevalence of multidrug-resistant MRSA with SCC
The first international surveillance study on epidemiology of CA-MRSA in Asian countries revealed important findings with regard to the current epidemiology of MRSA infections in the community and hospitals within Asia with multidrug-resistance rates at 73.1 and 83.7% for CA-MRSA and HA-MRSA, respectively [119]. At least, 357 isolates of CA-MRSA were analyzed with resistance rates of gentamicin, ciprofloxacin, and trimethoprim/sulfamethoxazole being significantly lower than those of HA-MRSA isolates, whereas resistance rates of clindamycin, erythromycin, and tetracycline were similarly high in both CA-MRSA and HA-MRSA [119, 120].
8. Conclusion
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