Robert J. Maier is the Georgia Research Alliance Professor of Microbial Physiology and has published more than 170 manuscripts on bacterial physiology and biochemistry, many involving roles of metalloenzymes and hydrogen metabolism enzymes. His work in the past 12 years has been focused on these attributes that aid survival of pathogenic bacteria within the host.


H2-oxidizing nickel-containing hydrogenases allow enteric and other pathogens to use H2 within host tissues, and aids pathogen survival within macrophages. Among the genes up-expressed by exposure of Salmonella enteric serovar Typhimurium to H2-a byproduct of intestinal commensal metabolism, are carbon uptake and catabolism-related genes. Glucarate, an oxidized product of glucose, is a major serum organic acid in humans, and it is readily detected in tissues and body fluids. Still, its role as a carbon source for a pathogen has not been studied. High-level expression of a potential glucarate permease gudT occurs when Salmonella is exposed to H2 gas. A gudT mutant strain of Salmonella is deficient in glucarate dependent growth, and it exhibits attenuated virulence (i.e. morbidity and mortality) in mice. The mean time of death for wild type-infected mice was two days earlier than for gudT-inoculated animals. At four days post inoculation, liver and spleen homogenates from gudT-inoculated mice contained fewer viable Salmonella than parental strain-inoculated animals. The parent strain grew well H2-dependently in a minimal medium with amino acids and glucarate as the primary C-sources, whereas the gudT strain achieved ~60% of the parent strains yield. Glucarate-mediated growth of a hyc mutant (cannot produce H2) was stimulated by H2, presumably due to the positive transcriptional response of added H2. Hydrogenase deficient Shigella flexneri exhibited poor acid tolerance but an energy deficiency response; compared to the H2-utilizing parent, it had increased production of glycolytic, nucleosidase, peptidase, and ATP synthase enzymes. Hydrogenases can be inhibited by nickel chelation approaches.

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