INHIBITION OF E.COLI DNA SYNTHESIS BY HYPOCHLOROUS ACID MAY MODEL THE BACTERICIDAL ACTIVITY OF PHAGOCYTES

Abstract

Phagocytic cells exert a rapid, selective inhibition of bacterial growth, followed by a more gradual degradation of cell components. Hypochlorous acid (HOC1), a. product of the “Oxidative Burst”, has been proposed as the agent responsible for bactericidal activity. HOC1, however, is generally characterized as a potent oxidant with nonselective destructive activity against all biomolecules. We designed a series of experiments to test the ability of HOC1 to inhibit E.coli growth in a discrete or selective manner. Our data indicate that at physiological concentrations (10-50μM) HOC1 exerts an irreversible bacteriostatic effect without coincident membrane disruption or extensive protein breakdown. Protein synthesis (incorporation of ³H-leucine) declines gradually over 15-30min, suggesting a secondary role in bacteriostasis. In contrast, DNA synthesis decreases by 50-80% in lmin, and by as much as 95% within 5min. E.coli (5×10⁸ cells/ml) ±50μM HOC1 were used to measure intracellular accumulation of ³H-thymidine (5mCi/ml) as well as incorporation into newly-synthesized (acid precipitable) DNA. Our data show that impaired incorporation of radioactivity precedes the decline in accumulation. We suggest that HOC1 may, indeed, function as a selective bactericidal agent in phagocytes, and may act by inhibition of DNA synthesis.

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