Re: MRSA Spreads in Households
Molecular tracing of the emergence, diversification, and transmission of S. aureus sequence type 8 in a New York community
Anne-Catrin Uhlemanna,1,2,
Janina Dordelb,1,
Justin R. Knoxa,
Kathy E. Ravenc,
Julian Parkhillb,
Matthew T. G. Holdenb,3,
Sharon J. Peacockb,c, and
Franklin D. Lowya,d
Author Affiliations
Edited by Alan G. Barbour, University of California, Irvine, CA, and accepted by the Editorial Board March 24, 2014 (received for review January 24, 2014)
Significance
A single clone, pulsed-field gel type USA300, has driven an unprecedented community-associated epidemic of Staphylococcus aureus infections, often affecting young, otherwise healthy individuals. Here we reconstruct the recent evolution and phylogeographic spread of USA300, using whole-genome sequencing of a large collection of infection and colonization isolates from a Manhattan community. We find that households serve as major reservoirs of persistence and transmission. By defining isolate variability within and between households, we localized putative transmission networks in the community. We further identified clonal spread of fluoroquinolone-resistant USA300, suggesting a critical role for antibiotic exposure in the recent evolution of this epidemic strain. Our study provides an important framework for molecular epidemiological investigations into the transmission of opportunistic pathogens that colonize and infect communities.
Abstract
During the last 2 decades, community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strains have dramatically increased the global burden of S. aureus infections. The pandemic sequence type (ST)8/pulsed-field gel type USA300 is the dominant CA-MRSA clone in the United States, but its evolutionary history and basis for biological success are incompletely understood. Here, we use whole-genome sequencing of 387 ST8 isolates drawn from an epidemiological network of CA-MRSA infections and colonizations in northern Manhattan to explore short-term evolution and transmission patterns. Phylogenetic analysis predicted that USA300 diverged from a most common recent ancestor around 1993. We found evidence for multiple introductions of USA300 and reconstructed the phylogeographic spread of isolates across neighborhoods. Using pair-wise single-nucleotide polymorphism distances as a measure of genetic relatedness between isolates, we observed that most USA300 isolates had become endemic in households, indicating their critical role as reservoirs for transmission and diversification. Using the maximum single-nucleotide polymorphism variability of isolates from within households as a threshold, we identified several possible transmission networks beyond households. Our study also revealed the evolution of a fluoroquinolone-resistant subpopulation in the mid-1990s and its subsequent expansion at a time of high-frequency outpatient antibiotic use. This high-resolution phylogenetic analysis of ST8 has documented the genomic changes associated with USA300 evolution and how some of its recent evolution has been shaped by antibiotic use. By integrating whole-genome sequencing with detailed epidemiological analyses, our study provides an important framework for delineating the full diversity and spread of USA300 and other emerging pathogens in large urban community populations.
http://www.pnas.org/content/early/2014/04/17/1401006111
