Document Detail


The inhibition of bacterial growth by hypochlorous acid. Possible role in the bactericidal activity of phagocytes.
MedLine Citation:
PMID:  2848494     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The 'respiratory burst' of phagocytes such as neutrophils generates superoxide which forms H2O2 by dismutation. H2O2 and Cl- ions serve as substrates for the enzyme myeloperoxidase to generate hypochlorous acid (HOCl). HOCl is thought to play an important role in bacterial killing, but its mechanism of action is not well characterized. Furthermore, although many studies in vitro have shown HOCl to be a damaging oxidant with little or no specificity (particularly at high concentrations), bacteria which have been ingested by phagocytes appear to experience a rapid and selective inhibition of cell division. Bacterial membrane disruption, protein degradation, and inhibition of protein synthesis, do not seem to occur in the early phases of phagocyte action. We have now found that low concentrations of HOCl exert a rapid and selective inhibition of bacterial growth and cell division, which can be blocked by taurine or amino acids. Only 20 microM-HOCl was required for 50% inhibition of bacterial growth (5 x 10(8) Escherichia coli/ml), and 50 microM-HOCl completely inhibited cell division (colony formation). These effects were apparent within 5 min of HOCl exposure, and were not reversed by extensive washings. DNA synthesis (incorporation of [3H]-thymidine) was significantly affected by even a 1 min exposure to 50 microM-HOCl, and decreased by as much as 96% after 5 min. In contrast, bacterial membrane disruption and extensive protein degradation/fragmentation (release of acid-soluble counts from [3H]leucine-labelled cells) were not observed at concentrations below 5 mM-HOCl. Protein synthesis (incorporation of [3H]leucine) was only inhibited by 10-30% following 5 min exposure to 50 microM-HOCl, although longer exposure produced more marked reductions (80% after 30 min). Neutrophils deficient in myeloperoxidase cannot convert H2O2 to HOCl, yet can kill bacteria. We have found that H2O2 is only 6% as effective as HOCl in inhibiting E. coli growth and cell division (0.34 mM-H2O2 required for 50% inhibition of colony formation), and taurine or amino acids do not block this effect. Our results are consistent with a rapid and selective inhibition of bacterial cell division by HOCl in phagocytes. H2O2 may substitute for HOCl in myeloperoxidase deficiency, but by a different mechanism and at a greater metabolic cost.
Authors:
S M McKenna; K J Davies
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Biochemical journal     Volume:  254     ISSN:  0264-6021     ISO Abbreviation:  Biochem. J.     Publication Date:  1988 Sep 
Date Detail:
Created Date:  1988-12-28     Completed Date:  1988-12-28     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  685-92     Citation Subset:  IM    
Affiliation:
Institute for Toxicology, University of Southern California, Los Angeles 90033.
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MeSH Terms
Descriptor/Qualifier:
Amino Acids / pharmacology
Bacterial Proteins / biosynthesis
Cell Membrane / drug effects
DNA, Bacterial / biosynthesis,  drug effects
Escherichia coli / drug effects*,  growth & development
Hydrogen Peroxide / pharmacology
Hypochlorous Acid / pharmacology*
Taurine / pharmacology
Grant Support
ID/Acronym/Agency:
E S 03598//PHS HHS; E S 03785//PHS HHS
Chemical
Reg. No./Substance:
0/Amino Acids; 0/Bacterial Proteins; 0/DNA, Bacterial; 107-35-7/Taurine; 7722-84-1/Hydrogen Peroxide; 7790-92-3/Hypochlorous Acid
Comments/Corrections

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