Researchers at the Texas A&M Health Science Center Institute of Biosciences and Technology at Houston have discovered a toxin present in the bacteria responsible for the current nationwide outbreak of staph infections also has a role in an aggressive pneumonia that is often fatal within 72 hours.
Their study is available online in Science Express and in an upcoming issue of the journal Science.
"The virulence of CA-MRSA (community-associated methicillin-resistant Staphylococcus aureus) strains that produce the PVL (Panton Valentine leukocidin) toxin presents a nightmare scenario," said M. Gabriela Bowden, Ph.D., research assistant professor at HSC-IBT and co-senior author. "If the community-acquired strain establishes itself in the hospital setting, it will be difficult to contain."
The most common cause of staph infections, S. aureus is a 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 their study, Dr. Bowden and her colleagues at the HSC-IBT Center for Extracellular Matrix Biology used mice to analyze S. aureus Panton Valentine leukocidin (PVL), a pore-forming toxin secreted by bacterial strains associated with both the current outbreak of CA-MRSA and necrotizing pneumonia.
CA-MRSA causes serious skin and soft tissue infections in healthy persons who have not been recently hospitalized or undergone invasive medical procedures, while necrotizing pneumonia destroys healthy lung tissue and can be fatal within 72 hours. With the PVL toxin, the bacterium also attacks infection-fighting white blood cells (leukocytes).
In the 1940s, the high mortality rate from S. aureus was abated by penicillin, but the bacteria soon developed a resistance. Methicillin provided new treatment options for infections in the late 1950s, but as of the late 1990s, it has become resistant.
In December, the United Kingdom had its first documented report of fatal necrotizing pneumonia cases caused by PVL-positive CA-MRSA. Eight hospitalized patients developed infections from CA-MRSA, and two died. It was previously believed the hospitals were free of these virulent strains of CA-MRSA.
Testing several bacterial strains, the HSC-IBT researchers learned PVL itself has an enhanced ability to disrupt cells in the body, and PVL-positive S. aureus has a greater capacity to attach to and colonize the lung, the latter resulting in necrotizing pneumonia.
"Our research shows in vivo that PVL is sufficient to cause pneumonia," Dr. Bowden said. "PVL-producing S. aureus overexpress other factors that enhance inflammation and bacterial attachment to the lung. These combined effects result in a vicious cycle of tissue destruction and inflammation, explaining the rapid onset and lethal outcome of this type of pneumonia."
Using these findings, the next step is additional studies to identify targets for potential development of therapies to treat S. aureus infections, including the PVL-positive strain.
"The present study underscores the aggressiveness of these strains and the urgent need to develop new strategies to battle these infections," Dr. Bowden said.
Other Science Express study contributors from the Center for Extracellular Matrix Biology were Magnus Hφφk, Ph.D., director and professor; Eric Brown, Ph.D., assistant professor (now at The University of Texas School of Public Health at Houston); Maria Labanderia-Rey, postdoctoral fellow; Vanessa Vazquez, graduate student; and Elena Barbu, graduate student. Florence Couzon, Sandrine Boisset, Michele Bes, Yvonne Benito, Jerome Etienne and Franηois Vandenesch from the University of Lyon and Hospices Civils de Lyon (France) also contributed.
Grants from the HSC, French Ministry of Research, National Institutes of Health, and Neva and Wesley West and Hamill Foundations supported this research.
The Texas A&M Health Science Center provides the state with health education, outreach and research. Its six components located in communities throughout Texas are Baylor College of Dentistry, the College of Medicine, the Graduate School of Biomedical Sciences, the Institute of Biosciences and Technology, the Irma Lerma Rangel College of Pharmacy, and the School of Rural Public Health.
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