By LEE BOWMAN
Scripps Howard News Service
July 12, 2005
The discovery offers a new target for drugs that could be used against bacteria that are becoming increasingly resistant to standard antibiotics, the scientists said.
"Instead of attempting to kill the bacteria directly with standard antibiotics, a treatment strategy to inhibit the Staph pigment would disarm the pathogen, making it susceptible to clearance by our normal immune defenses," said Dr. Victor Nizet, an infectious disease specialist at Children's Hospital, San Diego, and senior author of the study.
The team from the University of California-San Diego School of Medicine and Children's Hospital proved for the first time that the yellow-orange pigment allows Staphylococcus aureus (Latin for golden) to resist attack by white blood cells called neutrophils.
Doctors have long known that golden-colored strains of the bacteria tend to cause more disease that's harder to treat than colorless strains. Staph is the leading cause of human infection in the skin and soft tissue, bones and joints, abscesses and normal heart valves. It has become a particular problem in hospital settings, where it causes bloodstream and surgical wound infections.
The pigmentation reflects the germ's production of carotenoids, similar to those found in carrots and other colorful vegetables and fruits. The researchers found that the bugs use these antioxidants to inactivate chemicals released from the white blood cells that are lethal to most bacteria.
To confirm this, they eliminated genes that the bacteria use to synthesize the carotenoids, resulting in a mutant strain of Staph in a lab culture that appeared white rather than gold.
"We found that this nonpigmented Staph mutant became much more susceptible to oxidants, such as hydrogen peroxide and singlet oxygen produced by neutrophils," said Dr. George Liu, a research fellow at the medical school who led the study, which was published online by the Journal of Experimental Medicine.
"Without its golden pigment, the Staph lost its ability to survive in human neutrophils or blood and could no longer form an abscess when injected into the skin of experimental mice," Liu added.
In a further test, the researchers repeated the experiments with the mutant Staph strain in blood drawn from a patient with a rare inherited disorder in which neutrophils cannot produce oxidants, as well as in mice engineered to have the same defect.
Without the oxidant assault, the ability of the colorless strain to resist nuetrophils and produce disease was comparable to that seen in golden Staph infections.
Finally, the researchers gave another demonstration of the pigmentation's power by cloning a colorless strain Streptococcus bacterium that then turned yellow in color. This strain was also more resistant to oxidant and neutrophil killing and produced larger ulcers when injected into the skin of lab mice.
"The discovery of this critical role played by golden pigment ... provides a novel target for treatment of serious Staph infections," Nizet said.
The research also adds a new element to longstanding research on carotenoids, which many scientists hope can be used for their antioxidant properties to fight cancer or even slow the aging process.
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