A genomic portrait of the emergence, evolution, and global spread of a methicillin-resistant Staphylococcus aureus pandemic

Abstract

The widespread use of antibiotics in association with high-density clinical care has driven the emergence of drugresistant bacteria that are adapted to thrive in hospitalized patients. Of particular concern are globally disseminated methicillin-resistant Staphylococcus aureus (MRSA) clones that cause outbreaks and epidemics associated with health care. The most rapidly spreading and tenacious health-care-associated clone in Europe currently is EMRSA-15, which was first detected in the UK in the early 1990s and subsequently spread throughout Europe and beyond. Using phylogenomic methods to analyze the genome sequences for 193 S. aureus isolates, we were able to show that the current pandemic population of EMRSA-15 descends from a health-care-associated MRSA epidemic that spread throughout England in the 1980s, which had itself previously emerged from a primarily community-associated methicillin-sensitive population. The emergence of fluoroquinolone resistance in this EMRSA-15 subclone in the English Midlands during the mid-1980s appears to have played a key role in triggering pandemic spread, and occurred shortly after the first clinical trials of this drug. Genome-based coalescence analysis estimated that the population of this subclone over the last 20 yr has grown four times faster than its progenitor. Using comparative genomic analysis we identified the molecular genetic basis of 99.8% of the antimicrobial resistance phenotypes of the isolates, highlighting the potential of pathogen genome sequencing as a diagnostic tool. We document the genetic changes associated with adaptation to the hospital environment and with increasing drug resistance over time, and how MRSA evolution likely has been influenced by country-specific drug use regimens.

Differing epidemiology of two major healthcare-associated meticillin-resistant Staphylococcus aureus clones

“…CC239 was isolated frequently from respiratory tract specimens and patients with respiratory tract infections ( Table I) 10,13,[21][22][23] This study identified significant risk factors for CC22 relative to CC239, including older age, LTCF residence and admission to a subacute healthcare facility. In contrast, CC239 is primarily a nosocomial pathogen, with acquisition and transmission occurring within the acute care hospital system.…”

The role of vaccines in fighting antimicrobial resistance (AMR)

“…8 Likewise genomic analysis of S. aureus clinical isolates has been able to map the development of fluoroquinolone resistance to the timeframe and region where the first fluoroquinolone clinical trials were conducted. 9

10.1080/21645515.2018.1476814-F0001Figure 1.The rapid global spread of antibiotic resistant S. aureus , 78 C. difficile 8 and E. coli. 79 .

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How old are bacterial pathogens?

“…In recent years, comparative genomics has reconstructed the short-term evolutionary history of multiple bacterial clades whose diversity converges on a recent common ancestor (MRCA) that existed decades ago. One example is a clone of antibiotic-resistant Staphylococcus aureus that has been a common cause of hospital disease in Europe and other continents [1] (electronic supplementary material, table S1). Another example is food-borne gastroenteritis caused by Salmonella enterica serovar Agona, whose MRCA dates to the 1930s, and which spread globally in the 1960s via contaminated fish meal from South America [2].…”