Comparisons of resistance of CF and Non-CF pathogens to Hydrogen Peroxide and Hypochlorous Acid Oxidants In Vitro

PsA was relatively resistant to both H2O2 (LD50 = 1.5 mM) and HOCl (LD50 = 0.035 mM). SA was susceptible to H2O2 (LD50 = 0.1 mM) but resistant to HOCl (LD50 = 0.035 mM). Interestingly, KP was extremely resistant to high doses of H2O2 (LD50 = 2.5-5.0 mM) but was very sensitive to low doses of HOCl (LD50 = 0.015 mM). BC was intermediate to resist both oxidants: H2O2 (LD50 = 0.3-0.4 mM) and HOCl (LD50 = 0.025 mM). EC displayed the least resistance to H2O2 (LD50 = 0.2-0.3 mM) and HOCl (LD50 = 0.015 mM). The identified profile of H2O2-resistance was KP > PsA > BC > EC > SA and the profile of HOCl-resistance PsA > SA > BC > EC > KP. Moreover, both oxidants affected ATP production and membrane integrity of the cells. However, the effects varied among the tested organisms and, the oxidant-mediated damage correlated differentially with the bacterial viability.The order of HOCl-resistance identified herein best fits the clinical profile of CF infections. Even though oxidants are able to disrupt ATP production and cell membrane integrity, the degrees of damage vary among the organisms and correlate differentially with their viability.Cystic fibrosis (CF) is the most common fatal genetic disease in Caucasians and is caused by mutations of the CF transmembrane conductance regulator (CFTR), a cAMP-stimulated chloride (Cl-) channel [1]. The most devastating anomaly of CF is the lung disease which is characterized by chronic bacterial infection, abnormal airway inflammation, extensive neutrophil infiltration and small airway obstruction [2,3]. CF lung infection has a unique pathogen profile which is distinct from other lung infections. Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae, Stenotrophomonas maltophilia, Achromobacter xylosoxidans, Burkholderia cepacia are the most prevalent, among which P. aeruginosa predominates [4-6]. Strikingly, all the CF organisms except S. aureus are opportunistic pathogens, which do not cause infections in healthy hosts [6]. I