Role of Campylobacter jejuni Respiratory Oxidases and Reductases in Host Colonization

Abstract

Campylobacter jejuni is the leading cause of human food-borne bacterial gastroenteritis. The C. jejuni genome sequence predicts a branched electron transport chain capable of utilizing multiple electron acceptors. Mutants were constructed by disrupting the coding regions of the respiratory enzymes nitrate reductase (napA::Cm), nitrite reductase (nrfA::Cm), dimethyl sulfoxide, and trimethylamine N-oxide reductase (termed Cj0264::Cm) and the two terminal oxidases, a cyanide-insensitive oxidase (cydA::Cm) and cbb3-type oxidase (ccoN::Cm). Each strain was characterized for the loss of the associated enzymatic function in vitro. The strains were then inoculated into 1-week-old chicks, and the cecal contents were assayed for the presence of C. jejuni 2 weeks postinoculation. cydA::Cm and Cj0264c::Cm strains colonized as well as the wild type; napA::Cm and nrfA::Cm strains colonized at levels significantly lower than the wild type. The ccoN::Cm strain was unable to colonize the chicken; no colonies were recovered at the end of the experiment. While there appears to be a role for anaerobic respiration in host colonization, oxygen is the most important respiratory acceptor for C. jejuni in the chicken cecum.

Energy Taxis Drives Campylobacter jejuni toward the Most Favorable Conditions for Growth

“…To test this hypothesis, we studied the importance of electron transport in the tactic responses. Oxygen is the preferred terminal electron acceptor for C. jejuni under microaerophilic conditions (41,47), and a considerable reduction of the electron flow can therefore be obtained by blocking central enzymes of the oxygen-linked respiration. The tactic assay was consequently carried out in the presence of 37 M HQNO or 500 M sodium azide that are inhibitors of the cytochrome bc 1 complex and the primary terminal cytochrome c oxidase, respectively (25,36,43).…”

“…Interestingly, we observed that substances promoting attraction of C. jejuni NCTC11168 are all known to support the growth of C. jejuni and can be categorized as (i) metabolic substrates, including ␣-ketoglutamate, L-aspartate, L-aspargine, L-cysteine, L-glutamate, pyvuvate, and L-serine (17,34,45,48); (ii) electron donors, including formate, L-malate, Dlactate, and succinate; and (iii) electron acceptors, including fumarate, DMSO, nitrite, nitrate, and hydrogen peroxide (36,47). We observed a correlation between an attractant's potency and its efficiency as an energy source, since the preferred growth substrates L-serine and pyruvate (45) were the strongest attractants under microaerophilic conditions.…”

Nitrite Reductase NirBD Is Induced and Plays an Important Role during In Vitro Dormancy of Mycobacterium tuberculosis

“…This was proposed to be due to the production of nitrate and nitrite, which were subsequently used as terminal electron acceptors. Both nitrate and nitrite reductase mutants of Campylobacter jejuni showed reduced colonization of chickens (38).…”

Inactivation of the LysR regulator Cj1000 of Campylobacter jejuni affects host colonization and respiration

“…dcuA encodes an aspartate transporter and is directly downstream of aspA (Guccione et al, 2008). nrfA (cj1357c), which encodes a nitrite reductase, is also downregulated in the cj1000 mutant, but this enzyme was reported to be involved in nitrosative stress resistance, as well as in energy generation (Pittman et al, 2007;Weingarten et al, 2008).…”

“…Under microaerobic conditions, oxygen is reduced by either a low-O 2 -affinity CioAB oxidase or by a cytochrome cb9 oxidase (Jackson et al, 2007). This diversity is likely essential for the C. jejuni ability to colonize and survive in various ecological niches (Butcher et al, 2012;Weingarten et al, 2008).…”