Sodium nitrite-mediated killing of the major cystic fibrosis pathogens Pseudomonas aeruginosa, Staphylococcus aureus, and Burkholderia cepacia under anaerobic planktonic and biofilm conditions.
A hallmark of airways in patients with cystic fibrosis (CF) is highly refractory, chronic infections by several opportunistic bacterial pathogens. A recent study demonstrated that acidified sodium nitrite (A-NO(2)(-)) killed the highly refractory mucoid form of Pseudomonas aeruginosa, a pathogen that significantly compromises lung function in CF patients (S. S. Yoon et al., J. Clin. Invest. 116:436-446, 2006). Therefore, the microbicidal activity of A-NO(2)(-) (pH 6.5) against the following three major CF pathogens was assessed: P. aeruginosa (a mucoid, mucA22 mutant and a sequenced nonmucoid strain, PAO1), Staphylococcus aureus USA300 (methicillin resistant), and Burkholderia cepacia, a notoriously antibiotic-resistant organism. Under planktonic, anaerobic conditions, growth of all strains except for P. aeruginosa PAO1 was inhibited by 7.24 mM (512 μg ml(-1) NO(2)(-)). B. cepacia was particularly sensitive to low concentrations of A-NO(2)(-) (1.81 mM) under planktonic conditions. In antibiotic-resistant communities known as biofilms, which are reminiscent of end-stage CF airway disease, A-NO(2)(-) killed mucoid P. aeruginosa, S. aureus, and B. cepacia; 1 to 2 logs of cells were killed after a 2-day incubation with a single dose of ∼15 mM A-NO(2)(-). Animal toxicology and phase I human trials indicate that these bactericidal levels of A-NO(2)(-) can be easily attained by aerosolization. Thus, in summary, we demonstrate that A-NO(2)(-) is very effective at killing these important CF pathogens and could be effective in other infectious settings, particularly under anaerobic conditions where bacterial defenses against the reduction product of A-NO(2)(-), nitric oxide (NO), are dramatically reduced.
Major
Tiffany A
TA
Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati College of Medicine, 231 Sabin Way, Cincinnati, OH 45267, USA.
Panmanee
Warunya
W
Mortensen
Joel E
JE
Gray
Larry D
LD
Hoglen
Niel
N
Hassett
Daniel J
DJ
D000693:Anaerobiosis; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D016956:Burkholderia cepacia / Q000187:drug effects*; D003550:Cystic Fibrosis / Q000382:microbiology*; D008826:Microbial Sensitivity Tests; D018613:Microscopy, Confocal; D010933:Plankton / Q000187:drug effects*; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D012977:Sodium Nitrite / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D012977:Sodium Nitrite