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BIOLOGICAL SCIENCES / MICROBIOLOGY
Emergence of a bacterial clone with enhanced virulence by acquisition of a phage encoding a secreted phospholipase A₂

Izabela Sitkiewicz^*, Michal J. Nagiec^*,, Paul Sumby^*, Stephanie D. Butler, Colette Cywes-Bentley, and James M. Musser^*,¶

*Center for Molecular and Translational Human Infectious Diseases Research, Methodist Hospital Research Institute, Houston, TX 77030; Southwest Foundation for Biomedical Research, San Antonio, TX 78227; and Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115

Communicated by Richard M. Krause, National Institutes of Health, Bethesda, MD, September 1, 2006 (received for review July 20, 2006)

The molecular basis of pathogen clone emergence is relatively poorly understood. Acquisition of a bacteriophage encoding a previously unknown secreted phospholipase A₂ (designated SlaA) has been implicated in the rapid emergence in the mid-1980s of a new hypervirulent clone of serotype M3 group A Streptococcus. Although several lines of circumstantial evidence suggest that SlaA is a virulence factor, this issue has not been addressed experimentally. We found that an isogenic slaA mutant strain was significantly impaired in ability to adhere to and kill human epithelial cells compared with the wild-type parental strain. The mutant strain was less virulent for mice than the wild-type strain, and immunization with purified SlaA significantly protected mice from invasive disease. Importantly, the mutant strain was significantly attenuated for colonization in a monkey model of pharyngitis. We conclude that transductional acquisition of the ability of a GAS strain to produce SlaA enhanced the spread and virulence of the serotype M3 precursor strain. Hence, these studies identified a crucial molecular event underlying the evolution, rapid emergence, and widespread dissemination of unusually severe human infections caused by a distinct bacterial clone.

bacteria | Group A Streptococcus | Streptococcus pyogenes

Present address: Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599.

The authors declare no conflict of interest.

^¶To whom correspondence should be addressed. E-mail: jmmusser{at}tmh.tmc.edu

© 2006 by The National Academy of Sciences of the USA

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