Abraham Moller, United States of America

Emory University Department of Microbiology and Immunology

Author Of 1 Presentation

STREPTOCOCCUS PNEUMONIAE GENERATES HYDROXYL RADICALS TO RAPIDLY INTOXICATE AND KILL STAPHYLOCOCCUS AUREUS STRAINS (ID 256)

Abstract

Background

Streptococcus pneumoniae (Spn) strains rapidly kills Staphylococcus aureus (Sau) by producing membrane-permeable hydrogen peroxide (H2O2). The exact mechanism by which the H2O2-mediated killing occurs is not well understood.

Methods

An in vitro model that mimicked Spn-Sau contact during colonization of the upper airways and whole genome sequencing was conducted. Different Spn H2O2 mutants were constructed to confirm the Sau killing mechanism.

Results

Sau killing required outcompeting densities of Spn. A collection of MRSA/MSSA strains showed a linear sensitivity (R2=0.95) for Spn killing but the same strains had different susceptibilities when challenged against pure H2O2. WGS of these MRSA/MSSA strains revealed no association between clonal complex and susceptibility, or resistance, to Spn, or H2O2,respectively. A sublethal dose (~1 mM) of pure H2O2 when incubated with TIGR4DspxB eradicated cultures of Sau strains suggesting that Spn converts H2O2 to the hydroxyl radical (·OH). Accordingly, Sau killing was completely blocked by incubating with scavengers of ·OH radicals, DMSO, or thiourea.

Conclusions

Spn produces H2O2 which is rapidly converted to a more potent oxidant, the ·OH radical. Hydroxyl radicals does not affect Spn viability but rapidly intoxicate Sau strains. The target(s) of the ·OH radicals represents an exciting new alternative for the development of therapeutics against Sau infections.

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