Cited by 212Bacterial biofilms and quorum sensingCystic Fibrosis Research AdvancesInfections and bacterial resistance

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Anaerobic killing of mucoid Pseudomonas aeruginosa by acidified nitrite derivatives under cystic fibrosis airway conditions

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Yoon, S. S.·2006·Journal of Clinical Investigation

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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 (NO2) at pH 6.5, which mimics CF airway mucus. Killing required a pH lower than 7, implicating formation of nitrous acid (HNO2) and NO, that adds NO equivalents to cellular molecules. Eighty-seven percent of CF isolates possessed mucA mutations and were killed by HNO2 (3-log reduction in 4 days). Furthermore, antibiotic-resistant strains determined were also equally sensitive to HNO2. More importantly, HNO2 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 HNO2 for 16 days. HNO2 at these levels of acidity and NO2 also had no adverse effects on cultured human airway epithelia in vitro. In summary, selective killing by HNO2 may provide novel insights into the important clinical goal of eradicating mucoid P. aeruginosa from the CF airways.

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Authors: Yoon, S. S.
Affiliations: University of Cincinnati (US)
Corresponding author: Yoon, S. S.
ORCID: Yoon, S. S.
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2006-01-19
Volume: 116
Issue: 2
Pages: 436-446
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci24684
PMC: PMC1350997
OpenAlex: W2134475541
Cited by: 212
References: 59
Citations by year: 2026: 2 · 2025: 3 · 2024: 4 · 2023: 5 · 2022: 7 · 2021: 10 · 2020: 9 · 2019: 10 · 2018: 9 · 2017: 11 · 2016: 14 · 2015: 12 · 2014: 19 · 2013: 9 · 2012: 13
FWCI: 5.85
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by-nc-nd)
UNC Libraries
Funders: U.S. Department of Energy (DEAC-02-98CH10886, -AC02-98 CH 10886, DE-AC02-)
National Institutes of Health (5r01ai040541-05, DE-AC02-98CH10886)
National Institute of General Medical Sciences (GM-69845, R01GM069845)
National Institute of Allergy and Infectious Diseases (AI 40541, R01AI050812)
Basic Energy Sciences (DE-AC02, DEAC0298CH10886, AC02-98CH10886)
Brookhaven National Laboratory (AC-02-98CH10886, DE-AC02- 98CH10886)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
Health Sciences › Medicine › Microbiology (medical) › Infections and bacterial resistance
Keywords: Pseudomonas aeruginosa, cystic fibrosis, nitrite, nitrous acid, nitric oxide, biofilm, airway mucus, pH dependence, antibiotic resistance, chronic lung infection, airway epithelium
MeSH terms: Anaerobiosis, Animals, Bacterial Proteins, Cells, Cultured, Child, Child, Preschool, Cystic Fibrosis, Epithelial Cells, Humans, Hydrogen-Ion Concentration, Infant, Microbial Sensitivity Tests, Mucus, Nitrites, Pseudomonas aeruginosa, Pseudomonas Infections, Sputum, Biofilms, Respiratory Mucosa, Drug Resistance, Bacterial, Mice

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Anaerobic killing of mucoid Pseudomonas aeruginosa by acidified nitrite derivatives under cystic fibrosis airway conditions

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