Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Logo for

Science 325 (5946): 1380-1384

Copyright © 2009 by the American Association for the Advancement of Science

Endogenous Nitric Oxide Protects Bacteria Against a Wide Spectrum of Antibiotics

Ivan Gusarov, Konstantin Shatalin, Marina Starodubtseva, Evgeny Nudler*

Abstract: Bacterial nitric oxide synthases (bNOS) are present in many Gram-positive species and have been demonstrated to synthesize NO from arginine in vitro and in vivo. However, the physiological role of bNOS remains largely unknown. We show that NO generated by bNOS increases the resistance of bacteria to a broad spectrum of antibiotics, enabling the bacteria to survive and share habitats with antibiotic-producing microorganisms. NO-mediated resistance is achieved through both the chemical modification of toxic compounds and the alleviation of the oxidative stress imposed by many antibiotics. Our results suggest that the inhibition of NOS activity may increase the effectiveness of antimicrobial therapy.

Department of Biochemistry, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA.

* To whom correspondence should be addressed. E-mail: evgeny.nudler{at}nyumc.org

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Cellular Self-Defense: How Cell-Autonomous Immunity Protects Against Pathogens.
F. Randow, J. D. MacMicking, and L. C. James (2013)
Science 340, 701-706
   Abstract »    Full Text »    PDF »
Mechanism of [4Fe-4S](Cys)4 Cluster Nitrosylation Is Conserved among NO-responsive Regulators.
J. C. Crack, M. R. Stapleton, J. Green, A. J. Thomson, and N. E. Le Brun (2013)
J. Biol. Chem. 288, 11492-11502
   Abstract »    Full Text »    PDF »
Elucidating the Regulon of Multidrug Resistance Regulator RarA in Klebsiella pneumoniae.
S. De Majumdar, M. Veleba, S. Finn, S. Fanning, and T. Schneiders (2013)
Antimicrob. Agents Chemother. 57, 1603-1609
   Abstract »    Full Text »    PDF »
Methicillin-resistant Staphylococcus aureus Bacterial Nitric-oxide Synthase Affects Antibiotic Sensitivity and Skin Abscess Development.
N. M. van Sorge, F. C. Beasley, I. Gusarov, D. J. Gonzalez, M. von Kockritz-Blickwede, S. Anik, A. W. Borkowski, P. C. Dorrestein, E. Nudler, and V. Nizet (2013)
J. Biol. Chem. 288, 6417-6426
   Abstract »    Full Text »    PDF »
Evolution in Fast Forward: a Potential Role for Mutators in Accelerating Staphylococcus aureus Pathoadaptation.
G. S. Canfield, J. M. Schwingel, M. H. Foley, K. L. Vore, K. Boonanantanasarn, A. L. Gill, M. D. Sutton, and S. R. Gill (2013)
J. Bacteriol. 195, 615-628
   Abstract »    Full Text »    PDF »
Bacterial stress responses as determinants of antimicrobial resistance.
K. Poole (2012)
J. Antimicrob. Chemother. 67, 2069-2089
   Abstract »    Full Text »    PDF »
Eradication of bacterial persisters with antibiotic-generated hydroxyl radicals.
S. S. Grant, B. B. Kaufmann, N. S. Chand, N. Haseley, and D. T. Hung (2012)
PNAS 109, 12147-12152
   Abstract »    Full Text »    PDF »
S-Nitrosylation Signaling in Escherichia coli.
I. Gusarov and E. Nudler (2012)
Science Signaling 5, pe26
   Abstract »    Full Text »    PDF »
Antioxidant Strategies to Tolerate Antibiotics.
P. Belenky and J. J. Collins (2011)
Science 334, 915-916
   Abstract »    Full Text »    PDF »
H2S: A Universal Defense Against Antibiotics in Bacteria.
K. Shatalin, E. Shatalina, A. Mironov, and E. Nudler (2011)
Science 334, 986-990
   Abstract »    Full Text »    PDF »
Impaired lymphatic contraction associated with immunosuppression.
S. Liao, G. Cheng, D. A. Conner, Y. Huang, R. S. Kucherlapati, L. L. Munn, N. H. Ruddle, R. K. Jain, D. Fukumura, and T. P. Padera (2011)
PNAS 108, 18784-18789
   Abstract »    Full Text »    PDF »
Influence of Heme-Thiolate in Shaping the Catalytic Properties of a Bacterial Nitric-oxide Synthase.
L. Hannibal, R. Somasundaram, J. Tejero, A. Wilson, and D. J. Stuehr (2011)
J. Biol. Chem. 286, 39224-39235
   Abstract »    Full Text »    PDF »
Nitric Oxide Protects Bacteria from Aminoglycosides by Blocking the Energy-Dependent Phases of Drug Uptake.
B. D. McCollister, M. Hoffman, M. Husain, and A. Vazquez-Torres (2011)
Antimicrob. Agents Chemother. 55, 2189-2196
   Abstract »    Full Text »    PDF »
The actinobacteria-specific gene wblA controls major developmental transitions in Streptomyces coelicolor A3(2).
K. Fowler-Goldsworthy, B. Gust, S. Mouz, G. Chandra, K. C. Findlay, and K. F. Chater (2011)
Microbiology 157, 1312-1328
   Abstract »    Full Text »    PDF »
The Proximal Hydrogen Bond Network Modulates Bacillus subtilis Nitric-oxide Synthase Electronic and Structural Properties.
A. Brunel, A. Wilson, L. Henry, P. Dorlet, and J. Santolini (2011)
J. Biol. Chem. 286, 11997-12005
   Abstract »    Full Text »    PDF »
Angiotensin-converting Enzyme Overexpression in Mouse Myelomonocytic Cells Augments Resistance to Listeria and Methicillin-resistant Staphylococcus aureus.
D. Okwan-Duodu, V. Datta, X. Z. Shen, H. S. Goodridge, E. A. Bernstein, S. Fuchs, G. Y. Liu, and K. E. Bernstein (2010)
J. Biol. Chem. 285, 39051-39060
   Abstract »    Full Text »    PDF »
When It Comes to Antibiotics, Bacteria Show Some NO-how.
B. A. Patel and B. R. Crane (2010)
J Mol Cell Biol 2, 234-236
   Abstract »    Full Text »    PDF »
Antibiotic Sensitivity Profiles Determined with an Escherichia coli Gene Knockout Collection: Generating an Antibiotic Bar Code.
A. Liu, L. Tran, E. Becket, K. Lee, L. Chinn, E. Park, K. Tran, and J. H. Miller (2010)
Antimicrob. Agents Chemother. 54, 1393-1403
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882