Mutations in agr Do Not Persist in Natural Populations of Methicillin-Resistant Staphylococcus aureus

Bo Shopsin () 2 3 Christian Eaton 2 3 Gregory A. Wasserman 2 3 Barun Mathema 0 2 Rajan P. Adhikari 1 2 Simon Agolory 2 3 Deena R. Altman 2 3 Robert S. Holzman 2 3 Barry N. Kreiswirth 0 2 Richard P. Novick 1 2 0 Public Health Research Institute , Newark, New Jersey 1 Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine, New York University School of Medicine , New York , New York 2 Received 29 April 2010; accepted 11 June 2010; electronically published 13 October 2010. Potential conflicts of interest: B.S. has served as an advisor to and has received research support from Pfizer. All other authors report no potential conflicts. Presented in part: Gordon Conference on Staphylococcal Diseases , September 2009, Waterville Valley , New Hampshire. Financial support: American Heart Association Fellow-to-Faculty Transition Award (to B.S.); National Institutes of Health (grant R01-AI30138 to R.P.N.); Cystic Fibrosis Foundation (grant to B.S.). 540 First Ave, Second Floor, Lab 1 , New York, NY 10016 3 Department of Medicine, Division of Infectious Diseases Staphylococcus aureus organisms vary in the function of the staphylococcal virulence regulator gene agr. To test for a relationship between agr and transmission in S. aureus, we determined the prevalence and genetic basis of agr dysfunction among nosocomial methicillin-resistant S. aureus (MRSA) in an area of MRSA endemicity. Identical inactivating agr mutations were not detected in epidemiologically unlinked clones within or between hospitals. Additionally, most agr mutants had single mutations, indicating that they were short lived. Collectively, the results suggest that agr dysfunction is adaptive for survival in the infected host but that it may be counteradaptive outside infected host tissues. - m P a s n ittoaun icepemrcsuoe nuodW tuupSm tuupSm nuodW nuodW tuupSm tuupSm irneU nuodW tuupSm tuupSm loodB rseaN tuupSm nuodW ltooS tuupSm S M Acknowledgments We thank Karl Drlica and Joel Ernst for critical comments on the manuscript, Daniel Dykhuizen for helpful discussion, and Edward Geisinger for the gift of plasmids. (...truncated)