03 Dec Bacterial Nitric Oxide Essential For Staph Bacteria To Colonize Nose
MedicalResearch.com Interview with:
Ferric C. Fang, M.D.
Professor of Laboratory Medicine and Microbiology
Adjunct Professor of Medicine (Infectious Diseases)
Director, Harborview Medical Center Clinical Microbiology Laboratory
University of Washington School of Medicine
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The Fang lab has a longstanding interest in the interaction between nitric oxide (NO·) and pathogenic bacteria. NO· is an important mediator of the host innate immune response that restricts the growth of invading bacterial pathogens. One of the known actions of NO· is the reversible inhibition of aerobic respiration that results from NO· binding to the heme centers of terminal oxidases.
Like mammalian hosts, many bacteria also possess the ability to enzymatically synthesize NO·. Our latest research investigated the physiological role of the Staphylococcus aureus nitric oxide synthase (saNOS). We discovered that endogenously produced NO· is able to target bacterial terminal oxidases under microaerobic conditions, allowing the bacteria to transition to nitrate respiration when oxygen concentrations are limited and helping to maintain the membrane potential. This process was found to be essential for S. aureus nasal colonization in a mouse model. Thus, a conserved mechanism is involved in both the antimicrobial actions of NO· and the physiological role of NO· in regulating bacterial electron transfer reactions. Interestingly, NO·-heme interactions have been shown to control mitochondrial respiration during hypoxia in mammalian cells.
MedicalResearch.com: What should readers take away from your report?
Response: Mammalian and bacterial NO· synthases are structurally related; now we know that they are also functionally related. Our findings have identified a role for saNOS in bacterial physiology and pathogenesis that is likely to represent the primordial role for these enzymes in nature.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: Roughly one-third of the human population is colonized by S. aureus, and the nose is a common site of colonization. Colonized individuals may eventually develop invasive staphylococcal infections. Our findings suggest that the saNOS enzyme may be an attractive target for antimicrobial drugs that can eliminate S. aureus colonization and prevent staphylococcal infections. Future research can explore this possibility.
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Traci L. Kinkel, Smirla Ramos-Montañez, Jasmine M. Pando, Daniel V. Tadeo, Erin N. Strom, Stephen J. Libby, Ferric C. Fang. An essential role for bacterial nitric oxide synthase in Staphylococcus aureus electron transfer and colonization. Nature Microbiology, 2016; 2: 16224 DOI: 10.1038/nmicrobiol.2016.224
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