Cameron T. McDaniel, Warunya Panmanee, Geoffrey L. Winsor, Erin Gill, Claire Bertelli, Michael J. Schurr, Prateek Dongare, Andrew T. Paul, Seung-Hyun B. Ko, Gee W. Lau, Nupur Dasgupta, Amy L. Bogue, William E. Miller, Joel E. Mortensen, David B. Haslam, Phillip Dexheimer, Daniel A. Muruve, Bruce J. Aronow, Malcolm D. E. Forbes, Marek Danilczuk, Fiona S. L. Brinkman, Robert E. W. Hancock, Thomas J. Meyer, and Daniel J. Hassett
Antibiotic-resistant superbug bacteria represent a global health problem with no imminent solutions. Here we demonstrate that the combination (termed AB569) of acidified nitrite (A-NO2−) and Na2-EDTA (disodium ethylenediaminetetraacetic acid) inhibited all Gram-negative and Gram-positive bacteria tested. AB569 was also efficacious at killing the model organism Pseudomonas aeruginosa in biofilms and in ...
A Putative ABC Transporter Permease is Necessary For Resistance to Acidified Nitrite and EDTA in Pseudomonas aeruginosa Under Aerobic, Anaerobic, Planktonic or Biofilm Conditions
Pseudomonas aeruginosa (PA) is an important airway pathogen of cystic fibrosis and chronic obstructive disease patients. Multiply drug resistant PA is becoming increasing prevalent and new strategies are needed to combat such insidious organisms. We have previously shown that a mucoid, mucA22 mutant PA is exquisitely sensitive to acidified nitrite (A-NO2-, pH 6.5) at concentrations that are well tolerated in humans. Here, we used a transposon mutagenesis approach to identify PA mutants that are hypersensitive to A-NO2-. Among greater than 10,000 mutants screened, we focused on PA4455, in which the transposon was found to disrupt ...
Anaerobic killing of mucoid Pseudomonas aeruginosa by acidified nitrite derivatives under cystic fibrosis airway conditions
Sang Sun Yoon, Ray Coakley, Gee W. Lau, Sergei V. Lymar, Benjamin Gaston, Ahmet C. Karabulut, Robert F. Hennigan, Sung-Hei Hwang, Garry Buettner, Michael J. Schurr, Joel E. Mortensen, Jane L. Burns, David Speert, Richard C. Boucher, and Daniel J. Hassett
Published in The Journal of Clinical Investigation, February 1, 2006
Mucoid, mucA mutant Pseudomonas aeruginosa cause chronic lung infections in cystic fibrosis (CF) patients and are refractory to phagocytosis and antibiotics. Here we show that mucoid bacteria perish during anaerobic exposure to 15 mM nitrite (NO2–) at pH 6.5, which mimics CF airway mucus. Killing required a pH lower than 7, implicating ...