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bioRxiv · 10.1101/2022.11.29.517730

Non-redundant dimethyl sulfoxide reductases influence Salmonella enterica serotype Typhimurium anaerobic growth and virulence

Cruz, E.·Haeberle, A. L.·Westerman, T. L.·Durham, M. E.·Suyemoto, M. M.·Knodler, L. A.·Elfenbein, J. R.
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Abstract

Facultative anaerobic enteric pathogens can utilize a diverse array of alternate electron acceptors to support anaerobic metabolism and thrive in the hypoxic conditions within the mammalian gut. Dimethyl sulfoxide (DMSO) is produced by methionine catabolism and can act as an alternate electron acceptor to support anaerobic respiration. The DMSO reductase complex consists of three subunits, DmsA, DmsB, and DmsC, and allows bacteria to grow anaerobically with DMSO as an electron acceptor. The genomes of non-typhoidal S. enterica encode three putative dmsABC operons, but the impact of the apparent genetic redundancy in DMSO reduction on fitness of non-typhoidal S. enterica during infection remains unknown. We hypothesized that DMSO reduction would be needed for S. enterica serotype Typhimurium (S. Typhimurium) to colonize the mammalian gut. We demonstrate a S. Typhimurium mutant with loss of function in all three putative DMSO reductases ({Delta}dmsA3) poorly colonizes the mammalian intestine when the microbiota are intact and when inflammation is absent. DMSO reduction enhances anaerobic growth through non-redundant contributions of two of the DMSO reductases. Furthermore, DMSO reduction influences the expression of the type-3 secretion systems needed for virulence. Collectively, our data demonstrate that the DMSO reductases of S. Typhimurium are functionally non-redundant and suggest DMSO is a physiologically relevant electron acceptor that supports S. enterica fitness in the gut.

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Cruz, E., Haeberle, A. L., Westerman, T. L., Durham, M. E., Suyemoto, M. M., Knodler, L. A., Elfenbein, J. R.. 2022-11-30. Non-redundant dimethyl sulfoxide reductases influence Salmonella enterica serotype Typhimurium anaerobic growth and virulence. https://doi.org/10.1101/2022.11.29.517730

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