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bioRxiv · 10.1101/2020.05.25.115097

4-hydroxy-2-nonenal antimicrobial toxicity is neutralized by an intracellular pathogen.

Tabakh, H.·McFarland, A. P.·Pollock, A. J.·Glover, R. C.·Woodward, J. J.
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Abstract

Pathogens encounter numerous antimicrobial responses, including the reactive oxygen species (ROS) burst. ROS-mediated oxidation of host membrane poly-unsaturated fatty acids (PUFAs) generates the toxic alpha-beta carbonyl 4-hydroxy-2-nonenal (4-HNE). Though studied extensively in the context of sterile inflammation, 4-HNEs role during infection remains limited. Here we found that 4-HNE is generated during bacterial infection and that the intracellular pathogen Listeria monocytogenes induces a specific set of genes in response to 4-HNE exposure. A component of the L. monocytogenes 4-HNE response is the expression of the genes rha1 and rha2 which code for two NADPH-dependent oxidoreductases that collectively counter 4-HNE toxicity. Heterologous expression of rha1/2 in Bacillus subtilis significantly increased bacterial resistance to 4-HNE both in vitro and following phagocytosis by murine macrophages. Our work demonstrates that 4-HNE is a previously unappreciated component of ROS-mediated toxicity and that L. monocytogenes has evolved specific countermeasures to survive within its presence.

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Tabakh, H., McFarland, A. P., Pollock, A. J., Glover, R. C., Woodward, J. J.. 2020-05-25. 4-hydroxy-2-nonenal antimicrobial toxicity is neutralized by an intracellular pathogen.. https://doi.org/10.1101/2020.05.25.115097

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