WHAT:National Institutes of Health-funded scientists have determined the genome sequences of a dozen strains of Staphylococcus aureus bacteria known to be resistant to vancomycin, an antibiotic of last resort. The researchers demonstrated -that resistance arose independently in each strain, and identified shared features among the strains that may have helped them acquire vancomycin resistance and evade human immune defenses.
Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of hospital-acquired infections in the United States, causing an estimated 18,000 deaths in 2005, the most recent data available. Severe multidrug-resistant MRSA infections require treatment with last-line antibiotics such as vancomycin. Since 2002, 12 cases of vancomycin-resistant S. aureus (VRSA) have been documented in the United States, raising concern that staph infections might become untreatable if vancomycin resistance became widespread. Most of the VRSA cases arose in people with diabetes who had limb infections characterized by the presence of multiple kinds of bacteria, including vancomycin-resistant Enterococcus bacteria.
By comparing the genetic differences among 12 VRSA strains available for study, the researchers found that the strains last shared a common ancestor more than 50 years ago, well before the emergence of vancomycin resistance. The gene sequences showed that rather than spreading from person to person, vancomycin resistance appeared anew in each VRSA case. The team found that each VRSA strain acquired a bit of genetic material called transposon Tn1546, which likely came from vancomycin-resistant Enterococcus bacteria that simultaneously infected the patients.
All the VRSA strains belong to the CC5 family, or clade, of Staphylococcus. The CC5 clade is usually found in antibiotic-resistant hospital-acquired staph infections. The genome data showed that CC5 clade strains lack the ability to make a natural antibacterial colonizing factor, which is why they can co-exist with Enterococcus. The study also revealed that CC5 strains make proteins that disrupt a variety of human immune responses and allow the bacteria to flourish, increasing the odds that resistance factors will be transferred from Enterococcus to Staphylococcus bacteria in a mixed infection.
The genomes provided clues as to why person-to-person spread of VRSA has not become common. Without the ability to make or resist the antibacterial colonizing factor, CC5 clade members are at a disadvantage in any encounter with other naturally occurring staph strains that normally live on the skin and that do produce this factor.
The research was led by Michael S. Gilmore, Ph.D., of Harvard Medical School and the Massachusetts Eye and Ear Infirmary, and was conducted through the Harvard-wide Antibiotic Resistance Program, which is funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the NIH. Study collaborators included first author Veronica N. Kos, Ph.D., of Harvard Medical School, and bioinformatics experts from the NIAID-supported Broad Institute, based at the Massachusetts Institute of Technology.
VN Kos et al. Comparative genomics of vancomycin-resistant Staphylococcus aureus strains and their positions within the clade most commonly associated with methicillin-resistant S. aureus hospital-acquired infection in the United States. mBio DOI: 10.1128/mBio.00112-12 (2012).
NIAID Director Anthony S. Fauci, M.D., and Dennis M. Dixon, Ph.D. chief, Bacteriology and Mycology Branch, NIAID, are available to comment.
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This work was funded by NIH, NIAID, under grant number AI083214, and by the National Eye Institute, NIH, under grant number EY017381.
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