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According to the U.S. Centers for Disease Control and Prevention, about one in three humans carries Staphylococcus aureus “staph,” in their noses, and 2 percent carry the dreaded methicillin-resistant MRSA strain that thwarts common antibiotics. Researchers at the University of Washington School of Medicine have discovered why some people are not sick because of staphylococcus.
In a study in Cell Host & Microbe, the researchers show that an immune-system generated molecule called nitric oxide (NO) inhibits the ability of the S. aureus to transform from a relatively benign, quiescent colonizing state to its virulent form, producing toxins to invade and cause disease. This might explain why human nasal passages have very high concentrations of nitric oxide.
When antibiotic resistance is on the rise, immune molecules that target virulence factors could be used to develop new therapeutics, human immune system uses nitric oxide as a weapon against many microbes including viruses, parasites, bacteria and fungi. As with most antibiotics, nitric oxide fights most bacteria by limiting their ability to grow, but S. aureus is able to grow despite the presence of nitric oxide.
To find out how nitric oxide might be keeping S. aureus in check, the researchers set out to identify all the proteins in S. aureus that were modified by nitric oxide. Many proteins were altered, but AgrA protein plays a key role in the process that switches quiescent S. aureus bacteria into virulent invaders in a process called quorum sensing; it’s triggered when bacteria reach a certain density-a “quorum”and initiates the process in which the bacteria begin to produce virulent factors such as toxins. By modifying AgrA, nitric oxide blocked this quorum-sensing system.
To confirm the hypothesis, the researchers showed that mice with staphylococcal pneumonia that lacked the gene needed to generate nitric oxide developed more severe disease. This demonstrated that nitrix can suppress the production of toxins during an infection, the same effect may also apply when there is no ongoing infection. Bacteria often evolve so they can resist the effects of antibiotics, but curiously S aureus appears to have not evolved to resist the effect of nitric oxide.
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