Abstract
BackgroundIn the past decade, several countries have seen gradual replacement of endemic multi-resistant healthcare-associated methicillin-resistant Staphylococcus aureus (MRSA) with clones that are more susceptible to antibiotic treatment. One example is Singapore, where MRSA ST239, the dominant clone since molecular profiling of MRSA began in the mid-1980s, has been replaced by ST22 isolates belonging to EMRSA-15, a recently emerged pandemic lineage originating from Europe.ResultsWe investigated the population structure of MRSA in Singaporean hospitals spanning three decades, using whole genome sequencing. Applying Bayesian phylogenetic methods we report that prior to the introduction of ST22, the ST239 MRSA population in Singapore originated from multiple introductions from the surrounding region; it was frequently transferred within the healthcare system resulting in a heterogeneous hospital population. Following the introduction of ST22 around the beginning of the millennium, this clone spread rapidly through Singaporean hospitals, supplanting the endemic ST239 population. Coalescent analysis revealed that although the genetic diversity of ST239 initially decreased as ST22 became more dominant, from 2007 onwards the genetic diversity of ST239 began to increase once more, which was not associated with the emergence of a sub-clone of ST239. Comparative genomic analysis of the accessory genome of the extant ST239 population identified that the Arginine Catabolic Mobile Element arose multiple times, thereby introducing genes associated with enhanced skin colonization into this population.ConclusionsOur results clearly demonstrate that, alongside clinical practice and antibiotic usage, competition between clones also has an important role in driving the evolution of nosocomial pathogen populations.Electronic supplementary materialThe online version of this article (doi:10.1186/s13059-015-0643-z) contains supplementary material, which is available to authorized users.
Highlights
In the past decade, several countries have seen gradual replacement of endemic multi-resistant healthcare-associated methicillin-resistant Staphylococcus aureus (MRSA) with clones that are more susceptible to antibiotic treatment
This study focused on MRSA collected between 2000 and 2010 from the three main general hospitals: Singapore General Hospital, Tan Tock Seng Hospital and Changi General Hospital, which will subsequently be referred to as Hospital 1, Hospital 2 and Hospital 3, respectively (Figure S1A in Additional file 1)
Indications of distinct MRSA populations were based on observed differences in antibiotic resistance profiles; a clone resistant to multiple antibiotics [6] was being replaced by a clone resistant to fewer antibiotics
Summary
Several countries have seen gradual replacement of endemic multi-resistant healthcare-associated methicillin-resistant Staphylococcus aureus (MRSA) with clones that are more susceptible to antibiotic treatment. One of the most prevalent organisms causing healthcare-associated infections is Staphylococcus aureus [1]. This organism is part of the natural microbiota of humans, from which clones of epidemic drug-resistant S. aureus have emerged. HA-MRSA was first isolated in hospitals in Singapore in the late 1970s This was followed in the early 1990s by a sharp increase in prevalence, reaching a plateau in the late 1990s when approximately 40% of S. aureus isolated from inpatients with S. aureus infections were MRSA [6]. In 2006, a total of 3,517 non-duplicate MRSA isolates were cultured from clinical samples (497 from blood) from the 6 public sector hospitals in Singapore
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