de Lencastre, H. | bioRxiv Science

bioRxiv2017

Global phylogenomics of multidrug-resistant Staphylococcus aureus sequence type 772: the Bengal Bay clone

The global spread of antimicrobial resistance has been well documented in Gram-negative bacteria and healthcare-associated epidemic pathogens, often emerging from regions with heavy antimicrobial use. However, the degree to which similar processes occur with Gram-positive bacteria in the community setting is less well understood. Here we demonstrate the recent origin and global spread from the Indian subcontinent of a multidrug resistant Staphylococcus aureus lineage, sequence type 772 (Bengal Bay clone). Short-term outbreaks occurred following intercontinental transmission, typically associated with travel and family contacts, but ongoing endemic transmission was uncommon. Instrumental in the emergence of a single dominant clade in the early 1990s was the acquisition of a multidrug resistance integrated plasmid that did not appear to incur a significant fitness cost. The Bengal Bay clone therefore combines the multidrug resistance of traditional healthcare-associated clones with the epidemiological and virulence potential of community-associated clones.

genomics↗

bioRxiv2017

Methicillin resistant Staphylococcus aureus emerged long before the introduction of methicillin in to clinical practice

The spread of drug-resistant bacterial pathogens pose a major threat to global health. It is widely recognised that the widespread use of antibiotics has generated selective pressures that have driven the emergence of resistant strains. Methicillin-resistant Staphylococcus aureus (MRSA) was first observed in 1960, less than one year after the introduction of this second generation {beta}-lactam antibiotic into clinical practice. Epidemiological evidence has always suggested that resistance arose around this period, when the mecA gene encoding methicillin resistance carried on an SCCmec element, was horizontally transferred to an intrinsically sensitive strain of S. aureus. Whole genome sequencing a collection of the very first MRSA isolates allowed us to reconstruct the evolutionary history of the archetypal MRSA. Bayesian phylogenetic reconstruction was applied to infer the time point at which this early MRSA lineage arose and when SCCmec was acquired. MRSA emerged in the mid 1940s, following the acquisition of an ancestral type I SCCmec element, some fourteen years prior to the first therapeutic use of methicillin. Methicillin use was not the original driving factor in the evolution of MRSA as previously thought. Rather it was the widespread use of first generation {beta}-lactams such as penicillin in the years prior to the introduction of methicillin, which selected for S. aureus strains carrying the mecA determinant. Crucially this highlights how new drugs, introduced to circumvent known resistance mechanisms, can be rendered ineffective by unrecognised adaptations in the bacterial population due to the historic selective landscape created by the widespread use of other antibiotics.

microbiology↗