title: General mechanism for the bacterial toxicity of hypochlorous acid: abolition of ATP production.
abstract: The adenylate energy charges (EC) of Escherichia coli 25922, Pseudomonas aeruginosa 27853, and Streptococcus lactis 7962 rapidly fell in nutrient-rich media from values in excess of 0.9 to below 0.1 when the organisms were exposed to lethal levels of HOCl. The same cells maintained in energy-depleted states were incapable of attaining normal EC values necessary for biosynthesis and growth when challenged with nutrient energy sources after HOCl exposure. These changes correlated quantitatively with loss of replicative capabilities. Initial rates of transport of glucose, succinate, and various amino acids that act as respiratory substrates and the ATP hydrolase activity of the F1 complex from the ATP synthase of E. coli 25922 also declined in parallel with or preceded loss of viability. These results establish that cellular death is accompanied by complete disruption of bacterial ATP production by both oxidative and fermentative pathways as a consequence of inhibition of inner membrane bound systems responsible for these processes.
authors.affiliation: Department of Chemical and Biological Sciences, Oregon Graduate Center, Beaverton 97006-1999.
authors.forename: W C
authors.initials: WC
authors.lastname: Barrette
authors.forename: D M
authors.initials: DM
authors.lastname: Hannum
authors.forename: W D
authors.initials: WD
authors.lastname: Wheeler
authors.forename: J K
authors.initials: JK
authors.lastname: Hurst
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D001692:Biological Transport / Q000187:drug effects; D004734:Energy Metabolism; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D005285:Fermentation; D005947:Glucose / Q000493:pharmacokinetics; D006997:Hypochlorous Acid / Q000494:pharmacology*; D013294:Lactococcus lactis / Q000378:metabolism; D006180:Proton-Translocating ATPases / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000378:metabolism; D013386:Succinates / Q000493:pharmacokinetics
chemical_list: D013386:Succinates; D006997:Hypochlorous Acid; D000255:Adenosine Triphosphate; D006180:Proton-Translocating ATPases; D005947:Glucose