Journal article
Anaerobic killing of mucoid Pseudomonas aeruginosa by acidified nitrite derivatives under cystic fibrosis airway conditions
The Journal of clinical investigation, Vol.116(2), pp.436-446
01/26/2006
DOI: 10.1172/JCI24684
PMCID: PMC1350997
PMID: 16440061
Abstract
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 (NO
2
–
) at pH 6.5, which mimics CF airway mucus. Killing required a pH lower than 7, implicating formation of nitrous acid (HNO
2
) and NO, that adds NO equivalents to cellular molecules. Eighty-seven percent of CF isolates possessed
mucA
mutations and were killed by HNO
2
(3-log reduction in 4 days). Furthermore, antibiotic-resistant strains determined were also equally sensitive to HNO
2
. More importantly, HNO
2
killed mucoid bacteria (a) in anaerobic biofilms; (b) in vitro in ultrasupernatants of airway secretions derived from explanted CF patient lungs; and (c) in mouse lungs in vivo in a pH-dependent fashion, with no organisms remaining after daily exposure to HNO
2
for 16 days. HNO
2
at these levels of acidity and NO
2
–
also had no adverse effects on cultured human airway epithelia in vitro. In summary, selective killing by HNO
2
may provide novel insights into the important clinical goal of eradicating mucoid
P. aeruginosa
from the CF airways.
Details
- Title: Subtitle
- Anaerobic killing of mucoid Pseudomonas aeruginosa by acidified nitrite derivatives under cystic fibrosis airway conditions
- Creators
- Sang Sun Yoon - University of Cincinnati Medical CenterRay Coakley - University of North CarolinaGee W. Lau - University of CincinnatiSergei V. Lymar - Brookhaven National LaboratoryBenjamin Gaston - University of CincinnatiAhmet C. Karabulut - University of CincinnatiRobert F. Hennigan - Icahn School of Medicine at Mount SinaiSung-Hei Hwang - University of CincinnatiGarry Buettner - University of IowaMichael J. Schurr - Tulane UniversityJoel E. Mortensen - Cincinnati Children's Hospital Medical CenterJane L. Burns - Seattle Children's HospitalDavid Speert - University of British ColumbiaRichard C. Boucher - University of IowaDaniel J. Hassett - University of Cincinnati
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.116(2), pp.436-446
- Publisher
- American Society for Clinical Investigation
- DOI
- 10.1172/JCI24684
- PMID
- 16440061
- PMCID
- PMC1350997
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Language
- English
- Date published
- 01/26/2006
- Academic Unit
- Radiation Oncology
- Record Identifier
- 9984313087202771
Metrics
15 Record Views