IBT researchers create potential vaccine against dangerous staph infections

December 23, 2008

(HOUSTON) — Researchers at the Texas A&M Health Science Center Institute of Biosciences and Technology at Houston have created a vaccine based on the toxin Panton Valentine leukocidin (PVL) to protect mice from deep skin infections and pneumonia associated with a bacteria that are increasingly responsible for serious staph infections.

The study is currently available online in Clinical Microbiology and Infection and will be in an upcoming issue of the journal.

“Our present study is one step towards fulfilling the urgent need to develop new strategies to battle these aggressive infections,” said Gabriela Bowden, Ph.D., assistant professor in the Center for Extracellular Matrix Biology in the HSC-Institute of Biosciences and Technology and study senior author.

The most common cause of staph infections, Staphylococcus aureus is bacteria found on the skin or in the nose of about 25-30 percent of people. It also can be the culprit in minor skin infections like pimples and boils, as well as major diseases like meningitis, endocarditis, toxic shock syndrome and pneumonia.

In the 1940s, the high mortality rate from S. aureus was abated by penicillin, though the bacteria soon developed a resistance. Methicillin provided new treatment options for infections in the late 1950s, but resistant strains appeared by 1961.

These community-associated methicillin-resistant (CA-MRSA) strains cause serious infections in healthy persons not recently hospitalized or having undergone invasive medical procedures. The most sudden of all, necrotizing pneumonia, destroys healthy lung tissue and can be fatal in less than 72 hours. Producing the PVL toxin, the bacterium attacks infection-fighting white blood cells called leukocytes.

In this study, Dr. Bowden and her colleagues compared the virulence of the most prevalent CA-MRSA strain in the United States called “USA300” to its genetically identical PVL-deleted mutant. They found that PVL contributes to lung and muscle tissue destruction in necrotizing pneumonia and skin infections.

“Mice infected with the USA300 strain developed a dominant anti-PVL response,” Dr. Bowden said. “PVL subunits then were tested as vaccinogens against this clinical strain, and their efficacy correlated to both the route of vaccination and infection. Our data suggest that PVL is a virulence factor in CA-MRSA infections.”

Staphylococcal infections are becoming more virulent and affecting healthy children and young adults. Dr. Bowden is noted for her work in deciphering what virulence factors are present in these novel strains of S. aureus that allow easy dissemination within the community.

In fact, earlier studies by HSC-Institute of Biosciences and Technology researchers have shown that PVL itself can cause pneumonia. PVL-positive S. aureus also has a greater capacity to attach to and colonize the lung, the latter resulting in necrotizing pneumonia.

Research associate Priya Choudhury and graduate student Vanessa Vazquez in the HSC-Institute of Biosciences and Technology contributed to the Clinical Microbiology and Infection study. Also contributing were Eric L. Brown and Erin M. Koers of The University of Texas School of Public Health; and Oana Dumitrescu, Damien Thomas, Cedric Badiou, Jerome Etienne, Gerard Lina and Francois Vandenesch of the University of Lyon and Hospices Civils de Lyon (France).

Research support was provided by the Texas A&M Health Science Center Office of Research and the Hamill Foundation.

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