Host Hydrogen Rather than That Produced by the Pathogen Is Important for Salmonella enterica Serovar Typhimurium Virulence

Abstract

Salmonella enterica serovar Typhimurium utilizes molecular hydrogen as a substrate in various respiratory pathways, via H 2 -uptake enzymes termed Hya, Hyb, and Hyd. A different hydrogenase, the hydrogen-evolving Hyc enzyme, removes excess reductant during fermentative growth. Virulence phenotypes conferred by mutations in hyc genes, either alone or in combination with mutations in the H 2 -uptake enzyme genes, are addressed. Anaerobically grown ⌬hycB or ⌬hycC single-deletion strains were more sensitive to acid than the wild-type strain, but the ⌬hyc strains were like the virulent parent strain with respect to both mouse morbidity and mortality and in organ burden numbers. Even fecal-recovery numbers for both mutant strains at several time points prior to the animals succumbing to salmonellosis were like those seen with the parent. Neither hydrogen uptake nor evolution of the gas was detected in a hydrogenase quadruple-mutant strain containing deletions in the hya, hyb, hyd, and hyc genes. As previously described, a strain lacking all H 2 -uptake ability was severely attenuated in its virulence characteristics, and the quadruple-mutant strain had the same (greatly attenuated) phenotype. While H 2 levels were greatly reduced in ceca of mice treated with antibiotics, both the ⌬hycB and ⌬hycC strains were still like the parent in their ability to cause typhoid salmonellosis. It seems that the level of H 2 produced by the pathogen (through formate hydrogen lyase [FHL] and Hyc) is insignificant in terms of providing respiratory reductant to facilitate either organ colonization or contributions to gut growth leading to pathogenesis.

Site-directed mutagenesis of Campylobacter concisus respiratory genes provides insight into the pathogen’s growth requirements

“…g . mutants devoid of H 2 -uptake hydrogenase activity are viable under laboratory conditions 34 , 40 , 41 , 46 . It seems this is not the case for C .…”

Identification of a stable complex between a [NiFe]‐hydrogenase catalytic subunit and its maturation protease

“…The respiration of H 2 is important during the infection process followed by Salmonella enterica serovar Typhimurium . The S. enterica genome encodes four [NiFe]‐hydrogenases, termed Hyd‐1, Hyd‐2, Hyd‐3, and Hyd‐5.…”

“…The S. enterica Hyd‐5 isoenzyme shares structural similarities with Hyd‐1, but is synthesized under aerobic conditions and mouse model studies have shown that S . enterica Hyd‐5 is expressed during infection .…”

Preliminary Transcriptome Analysis of Mature Biofilm and Planktonic Cells of Salmonella Enteritidis Exposure to Acid Stress

“…Typhimurium, can remove excess reductant generated during acid stress by producing H 2 and consuming protons, so the expression of hydrogenase is likely involved in the pH response and regulation (Zbell and Maier, 2009 ; Noguchi et al, 2010 ). HycA is thought to regulate the Hyc operon, HycD is a transmembrane protein, HycE is the Ni-containing large subunit of Hyc-hydrogenase, and HycI is known to play an important role in the maturation of the formate hydrogenlyase (FHL) complex (Lamichhane-Khadka et al, 2015 ). In the present study, the HycADEHI genes were up-regulated in aTF, with log2 fold changes of 2.1 to 3.7, and all of these genes are associated with hydrogenase.…”