Inhibition of protein synthesis may explain the bactericidal properties of hypochlorous acid produced by phagocytic cells
The authors find that hypochlorous acid (HOCl) and hydrogen peroxide (H/sub 2/O/sub 2/) inhibit protein synthesis in E. coli: HOCl is similarly ordered 10x more efficient than H/sub 2/O/sub 2/. This result may underlie the mechanism of bacterial killing by phagocytes, which use H/sub 2/O/sub 2/ and myeloperoxidase (MPO) to oxidize Cl/sup -/ to HOCl. Protein synthesis (/sup 3/H-leu incorporation) was completely inhibited by 50..mu..M HOCl, whereas 50..mu..M H/sub 2/O/sub 2/ only gave similarly ordered 10% inhibition. Complete inhibition by H/sub 2/O/sub 2/ was only observed at concentrations < 0.5 mM. HOCl was also a more potent inhibitor of cell growth (cultured in M9 medium + glucose) than was H/sub 2/O/sub 2/. No growth occurred at 50..mu..M HOCl: in contrast 0.5 mM H/sub 2/O/sub 2/ was required for similar results. During time-course experiments it was found that the inhibition of cell growth by both HOCl and H/sub 2/O/sub 2/ reached a maximum within 30 min (at any concentration used). HOCl reacts avidly with amino groups to form N-chloroamines but H/sub 2/O/sub 2/ is unreactive. Amino acids (ala, lys, met, trp) or taurine (all at 10 mM) prevented the effects of HOCl but did not affect H/sub 2/O/sub 2/ results. There was an excellent correlation between decreased protein synthesis and diminished cell growth. Inhibition of cell growth was not explained by proteolysis (release of acid-soluble counts), or by loss of membrane integrity. They propose that inhibition of protein synthesis may be a fundamental aspect of the bactericidal functions of phagocytes, and that the production of HOCl by MPO represents a quantitative advantage over H/sub 2/O/sub 2/.
- Research Organization:
- Univ. of Southern California, Los Angeles
- OSTI ID:
- 6933226
- Report Number(s):
- CONF-8606151-
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:6; Conference: 76. annual meeting of the Federation of American Society for Experimental Biology, Washington, DC, USA, 8 Jun 1986
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
ESCHERICHIA COLI
GROWTH
HYDROGEN PEROXIDE
BIOLOGICAL EFFECTS
HYPOCHLOROUS ACID
PHAGOCYTES
BIOLOGICAL FUNCTIONS
PROTEINS
BIOSYNTHESIS
AMINO ACIDS
CELL MEMBRANES
INHIBITION
PHAGOCYTOSIS
TAURINE
TRACER TECHNIQUES
TRITIUM COMPOUNDS
AMINES
ANIMAL CELLS
BACTERIA
CARBOXYLIC ACIDS
CELL CONSTITUENTS
FUNCTIONS
HYDROGEN COMPOUNDS
INORGANIC ACIDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MEMBRANES
MICROORGANISMS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
OXYGEN COMPOUNDS
PEROXIDES
SOMATIC CELLS
SULFONIC ACIDS
SYNTHESIS
560300* - Chemicals Metabolism & Toxicology
550201 - Biochemistry- Tracer Techniques