Of the organisms tested, all except PsA demonstrated significant decline in ATP production which correlated with loss of CFU viability; ATP production in PsA declined significantly Capmatinib cost up to 5 mM but did not correlated with decline in CFU viability. These data present evidence that H2O2 affects ATP production in bacteria suggesting that there are H2O2-sensitive sites in the bacterial ATP production machinery or that H2O2 assault disrupts pathways of energy production. The profile of abolished ATP production with HOCl treatment was different from that of H2O2 in that HOCl-induced loss of ATP production correlated significantly

with the loss of CFU viability in PsA, BC, and EC, while these two parameters were statistically independent in SA and KP (Figure 5). Interestingly, ATP production in KP was unaffected by HOCl concentrations up to

0.1 mM, a dose GDC-0941 concentration exceeding that required for complete eradication of the entire samples at the cellular densities used herein. Given the I BET 762 results obtained in SA and KP, it can be inferred that loss of CFU viability is not completely dependent on disruption of ATP production. In light of these results, further studies are required to elucidate the specific mechanisms of oxidant-induced bactericidal activity against different bacterial species. Conclusions We have demonstrated that the HOCl-resistance profile of microorganisms relates to its clinical pathogenicity in CF lung disease. Therefore, defective oxidant-mediated phagocytic host defense in CF may predispose the patient to chronic infections, especially those caused by PsA.

Furthermore, oxidants affect bacterial membrane permeability and ATP energy production. But the effects are organism-specific, indicating that varied survival advantages exist among Glutamate dehydrogenase the bacteria when they are phagocytosed and encounter phagocyte-produced oxidants. Acknowledgements The work was supported by the grant from the National Institutes of Health to G. Wang (R01 AI72327). References 1. Collins FS: Cystic fibrosis: molecular biology and therapeutic implications. Science 1992,256(5058):774–779.PubMedCrossRef 2. Welsh MJ, Ramsey BW, Accurso F, Cutting G: Cystic Fibrosis. In Metabolic and Molecular Basis of Interited Disease. 8th edition. Edited by: Scriver CR. New York: McGraw-Hill; 2001:5121–5188. 3. Davis PB, Drumm M, Konstan MW: Cystic fibrosis. Am J Respir Crit Care Med 1996,154(5):1229–1256.PubMed 4. Sadikot RT, Blackwell TS, Christman JW, Prince AS: Pathogen-host interactions in Pseudomonas aeruginosa pneumonia. Am J Respir Crit Care Med 2005,171(11):1209–1223.PubMedCrossRef 5. Foundation CF: Cystic Fibrosis Foundation Patient Rigestry: 2009 Annual Data Report. [http://​www.​cff.​org/​UploadedFiles/​research/​ClinicalResearch​/​Patient-Registry-Report-2009.​pdf] 6. Gibson RL, Burns JL, Ramsey BW: Pathophysiology and management of pulmonary infections in cystic fibrosis. Am J Respir Crit Care Med 2003,168(8):918–951.