This month's Genome Watch looks at how the combination of household contact sampling and whole-genome sequencing has provided insight into the sources and transmission patterns of methicillin-resistant Staphylococcus aureus clone USA300.
Staphylococcus aureus is a Gram-positive bacterium that, in humans, is frequently found in the upper respiratory tract and on the skin. Methicillin-resistant S. aureus (MRSA) was first described in the 1960s, and it has become increasingly widespread; MRSA is resistant to β-lactam antimicrobials and is frequently resistant to other antimicrobials as well. MRSA is often associated with outbreaks in healthcare facilities, but it can also cause disease in the community, predominantly skin and soft tissue infections (SSTIs), as well as more serious disease1. In the United States, it is estimated that community-acquired MRSA incurs a cost to society of US$1.4–$13.8 billion per year2. In recent years, the MRSA USA300 clone has become the most common cause of community-acquired MRSA in the United States. In order to control MRSA, it is crucial to understand what the sources of infection are and how MRSA is transmitted, and recent whole-genome sequencing (WGS) studies have provided insight into these mechanisms for the USA300 clone.
In a study investigating an epidemiological network of USA300 infections in New York City, United States, Uhlemann et al. sequenced 387 putative USA300 isolates from screened cases, controls, household members and household environments, using the Illumina HiSeq platform3. Comparison of single-nucleotide polymorphisms (SNPs) from the different isolates showed that the median pair-wise SNP distance between any two isolates from the community was 104 (that is, the median difference between any two isolates was 104 SNPs), whereas isolates from the same household were more closely related, with a median difference of three SNPs. A small number of inter-household transmission events could also be identified based on this analysis. Overall, these data suggest that there were multiple introductions of USA300 into the community and, by contrast, a single USA300 clone was typically introduced per household, which then acted as a reservoir of infection for household members.
Further investigating the role of household reservoirs, Alam et al. performed WGS on 146 isolates of USA300 taken from 21 index patients with SSTIs and their household contacts in Chicago and Los Angeles, United States, using the Illumina HiSeq platform4. Each household was visited and members sampled three times: a baseline visit shortly after treatment of the SSTI with follow-ups at 3 months and 6 months after the initial visit. In agreement with the previous study3, isolates from the same household were very similar to each other, confirming that a single USA300 introduction occurred at each residence. Inspection of a minimum spanning tree based on the core protein clusters of the isolates indicated that many of the isolates from the index patients were derived from an existing population of USA300 within the household, rather than being the introductory isolate. Use of a time-scaled phylogeny approach provided additional evidence of long-term persistence of USA300 within households. This analysis revealed that, prior to the sampling of the index patient, USA300 had existed in these households for approximately 2–8 years.
These studies have shown how, in different parts of the United States, a common epidemiological reservoir of MRSA USA300 can be detected. By contrast, the resistance of the USA300 isolates to other antimicrobials seemed to differ by geographical region, with fluoroquinolone resistance being at a relatively high prevalence in New York City and Los Angeles, but at a relatively low prevalence in Chicago3,4. Nonetheless, theconsensus on the importance of asymptomatic colonization and household transmission in the maintenance of USA300 across the country suggests that these two factors should be considered as targets for measures designed to control the transmission of this MRSA clone. If eradication is the goal, it will be important to include not only patients with clinical cases of MRSA for decolonization, but also their household contacts and family members.
Huang, H. et al. Comparisons of community-associated methicillin-resistant Staphylococcus aureus (MRSA) and hospital-associated MSRA infections in Sacramento, California. J. Clin. Microbiol. 44, 2423–2427 (2006).
Lee, B. Y. et al. The economic burden of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA). Clin. Microbiol. Infect. 19, 528–536 (2013).
Uhlemann, A. C. et al. Molecular tracing of the emergence, diversification, and transmission of S. aureus sequence type 8 in a New York community. Proc. Natl Acad. Sci. USA 111, 6738–6743 (2014).
Alam, M. T. et al. Transmission and microevolution of USA300 MRSA in U.S. households: evidence from whole-genome sequencing. mBio. 6, e00054–15 (2015).
The author declares no competing financial interests.