|Miller, William - Bill|
Submitted to: Antonie Van Leeuwenhoek
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/11/2007
Publication Date: 6/29/2007
Citation: Kaakoush, N.O., Sterzenbach, T., Miller, W.G., Suerbaum, S., Mendz, G.L. 2007. Identification of disulphide reductases in campylobacterales. Antonie Van Leeuwenhoek. 92(4):429-441 Interpretive Summary: Several members of the bacterial order Campylobacterales are human pathogens: Campylobacter jejuni is the major cause of bacterial food poisoning in the world and Helicobacter pylori is the causal agent of ulcers. The majority of bacteria within Campylobacterales live in low-oxygen environments. Thus, the presence of oxygen imposes stress on these bacteria and mechanisms have evolved to modulate the oxidation state within the cell. In bacteria, disulphide reducatases have been proposed as one mechanism in which bacterial cells modulate the intracellular redox state. Disulphide reductases can be identified by the presence of a four amino acid motif within the protein. Members of the Campylobacterales, as well as other bacterial groups, were examined for the presence of these reductases. The thioredoxin disulphide reductases of the Campylobacterales were found to be highly related. One group of these reductases were found to be more similar to reductases found in humans and parasites (such as the malaria parasite) than to another group of bacterial thioredoxin reductases. Antibiotics have been developed against parasite reductases, suggesting a possible mode of action for novel antimicrobials that target these Campylobacterales pathogens.
Technical Abstract: Disulphide reductases of host-colonising bacteria are involved in the expression of virulence factors, resistance to drugs, and elimination of compounds toxic to the microorganisms. The four species Campylobacter jejuni, Helicobacter pylori, Wolinella succinogenes and Arcobacter butzleri of the order Campylobacterales colonise the gastrointestinal tract of higher animals. The kinetic parameters of the total disulphide reduction activities of these four bacterial species were measured, the enzyme activities had similar Km values, but their Vmax showed two different sets of values. Genome analyses served to identify putative disulphide reductases in these four species. Three different filters applied to the genomes of C. jejuni, H. pylori, W. succinogenes and A. butzleri yielded 32, 25, 26 and 33 genes, respectively, encoding proteins with the characteristics of disulphide reductases. The thioredoxin reductases TrxB1 and TrxB2 of the four Campylobacterales clustered together in phylogenetic trees. Their TrxB1 proteins were more closely related to those of Firmicutes than to the corresponding proteins of other Proteobacteria. The Campylobacterales TrxB2 proteins were closer to glutathione reductases of other organisms than to their respective TrxB1 proteins. Notwithstanding the different habitats of the four bacteria, the study demonstrated similarities between their disulphide reductases. The common phylogenetic features of the Campylobacterales thioredoxin reductases suggested a special role for these enzymes in the physiology of these bacteria.