Review
Prevalence and genotype distribution of methicillin-resistant Staphylococcus aureus (MRSA) in India

https://doi.org/10.1016/j.jgar.2016.07.008Get rights and content

Highlights

  • MRSA is as pervasive in India as it is worldwide.

  • The majority of HA-MRSA belong to SCCmec III ST239 genotype.

  • CA-MRSA mostly belong to SCCmec IV ST22, SCCmec V ST772 and SCCmec V ST672 genotypes.

  • HA-MRSA are becoming more invasive and vancomycin-resistant.

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is a serious human pathogen that can cause a wide variety of infections. Comparative genetic analyses have led to the discovery that despite the existence of a vast number of genotypes, outbreak strains of MRSA appear to be limited to certain genotypes, some of which are further restricted to certain geographical locations. Whereas extensive literature is available in several countries, the complexity of the clonal distribution both of healthcare-associated (HA) and community-associated (CA) MRSA in India is only now beginning to be understood. Studies have revealed that MRSA in India is distributed among all of the major staphylococcal cassette chromosome mec (SCCmec) types. The majority of HA-MRSA isolates belong to SCCmec type III and sequence type (ST) 239. By contrast, CA-MRSA mostly belong to ST22 (SCCmec IV), ST772 (SCCmec V) and ST672 (SCCmec V) genotypes. Similar to the global scenario, CA-MRSA is becoming more invasive and transmissible and is increasingly becoming difficult to be differentiated from HA-MRSA. In addition, it is disturbing that some of the HA-MRSA isolates have been reported to be vancomycin-resistant. On the other hand, almost no information is available on the genotypes of livestock-associated MRSA or their potential impact on human infections in India. Concerted efforts are needed to further understand the genetic epidemiology of MRSA in India.

Introduction

Staphylococcus aureus is a highly versatile and adaptive pathogen that causes a wide spectrum of diseases ranging from minor local infections to fatal systemic syndromes [1]. The success of S. aureus as a pathogen is due to its ability to express various types of virulence factors and to form biofilm. These determinants not only help S. aureus to invade the host but also to resist the action of antimicrobials and host defence mechanisms, facilitating the establishment of persistent and recurring infections [2], [3], [4]. These properties make S. aureus a resilient pathogen and, not surprisingly, methicillin-resistant S. aureus (MRSA) has become one of the most significant nosocomial pathogens worldwide today. The first description of MRSA was in the UK in 1961, and this was followed soon thereafter by reports elsewhere—in Europe in 1965, in Australia in 1966, in the USA in 1968 and in Asia in the 1970s [5], [6].

MRSA can be genotyped by one or more of several molecular techniques [7], including pulsed-field gel electrophoresis (PFGE) [8], multilocus sequence typing (MLST) [9] (http://saureus.mlst.net), staphylococcal protein A (spa) typing [10] (http://spaserver.ridom.de) and staphylococcal cassette chromosome mec (SCCmec) typing [11]. The different typing techniques are employed for different purposes. PFGE and spa typing are very useful for short-term epidemiological studies, whereas MLST, which can be applied to phylogenetic analyses, can be used for longitudinal and long-term studies. PFGE is a PCR-independent technique where chromosomal DNA is subjected to restriction digestion followed by electrophoresis under an alternating voltage gradient. PFGE used to be the gold standard to investigate MRSA outbreaks in hospitals as well as to probe hospital-to-hospital transmission. However, in addition to poor extrapolation between laboratories, some studies have reported that PFGE is less reproducible and therefore less useful for long-term surveillance [12]. These drawbacks can be overcome by MLST, which involves PCR amplification and sequencing of seven housekeeping genes followed by allelic profiling and assigning of sequence types (STs) to each strain. Further, groups of STs in which every ST shares at least five of seven identical alleles with at least one other ST in the group are referred to as clonal complexes (CCs). Although laborious, MLST has been reported to be a useful tool for studying the phylogenetic relationship and evolutionary biology of isolates. Discrimination between strains and extrapolation of data between laboratories can also be achieved by spa typing, which involves PCR and sequencing for the single locus of spa as opposed to seven loci for MLST. MRSA can also be classified by SCCmec typing, which involves PCR for one or more of the mec, ccr, cch and ccu loci. As of 28 June 2016, 3112 STs (http://saureus.mlst.net/sql/sthtml.asp), 16 071 spa types (http://www.spaserver.ridom.de/) and 11 SCCmec types (I through XI, some further subclassified into A, B, C1, C2 and E) (http://www.sccmec.org/Pages/SCC_TypesEN.html) have been identified.

Outbreak strains of MRSA, which can cause a sudden rise in the incidence of infections, can be grouped into hospital/healthcare-associated (HA) or community-associated (CA) MRSA. Traditionally, HA-MRSA is considered to be of nosocomial origin and usually causes infections upon prolonged hospitalisation or in patients with indwelling devices, or those undergoing dialysis, surgery, or antimicrobial or immunosuppressive therapy [13]. By contrast, CA-MRSA strains originate from healthy individuals with no risk factors or previous healthcare contact and constitute a major proportion of skin and soft-tissue infections (SSTIs) [14]. CA-MRSA is typically susceptible to most antibiotics except methicillin and β-lactams [15]. Genotypically, HA-MRSA mainly carry SCCmec types I, II and III (1B, 2A and 3A in the newly proposed nomenclature), whilst CA-MRSA generally carry SCCmec types IV and V (2B and 5C2) [16].

A vast amount of information is available from several countries on the prevalence of MRSA. It has been observed that several clones have circulated or have been circulating in different parts of the world. These include the USA (100, 200, 300, etc.), the epidemic MRSA (EMRSA-1, −15, −16, etc.), the Western Australia (WA) and the Canadian MRSA (CMRSA) series as well as other clones, each of which harbour a few characteristic genetic loci [17].

Remarkably, a restricted number of genotypes appear to dominate specific outbreaks, sometimes in particular geographical areas. Of late, however, some of the clones have spread beyond their initial geographic boundaries [17]. It would be interesting and important to map and characterise the global distribution of genotypes in order to not only elucidate evolutionary relationships and movement of clones from one place to another, but also to design potential intervention strategies. However, data from developing and resource-constrained countries are scarce. This review presents the current knowledge about genotype and sequence characteristics of MRSA in India.

Section snippets

Literature search

PubMed, Medline and Google Scholar were mined for the search terms ‘MRSA’, ‘genotype’, ‘prevalence’ and/or ‘India’ and 361 abstracts and 205 manuscripts published between 1990 and 2016 were identified for inclusion in this review. After reviewing all of the relevant abstracts and articles, 86 full-length articles containing unambiguous genotyping information based on at least one of the methodologies described above were considered for discussion.

Conclusions

It is becoming clear that MRSA is as pervasive in India as it is worldwide and that both HA-MRSA and CA-MRSA are prevalent. Although certain spa types may be more frequent, MRSA from India are distributed among all of the SCCmec types. The majority of HA-MRSA belong to SCCmec III ST239, whereas CA-MRSA mostly belong to SCCmec IV ST22, SCCmec V ST772 and SCCmec V ST672 genotypes (Table 2). Similar to trends globally, CA-MRSA infections as well as vancomycin resistance appear to be on the rise in

Conflicts of interest

The authors certify that they have no affiliations with or involvement in any organization or entity with any interest, financial or non-financial, in the subject matter or materials discussed in this manuscript.

Funding

None.

Ethical approval

Not required.

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    Present address: Center for Immunology and Microbial Diseases, MS-251, Albany Medical College, 47 New Scotland Avenue, Albany, NY 12208, USA.

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