Utilization of host-derived cysteine-containing peptides overcomes the restricted sulphur metabolism of Campylobacter jejuni

The non-glycolytic food-borne pathogen Campylobacter jejuni successfully colonizes the intestine of various hosts in spite of its restricted metabolic properties. While several amino acids are known to be used by C. jejuni as energy sources, none of these have been found to be essential for growth. Here we demonstrated through phenotype microarray analysis that cysteine utilization increases the metabolic activity of C. jejuni. Furthermore, cysteine was crucial for its growth as C. jejuni was unable to synthesize it from sulphate or methionine. Our study showed that C. jejuni compensates this limited anabolic capacity by utilizing sulphide, thiosulphate, glutathione and the dipeptides Glu-Cys, Cys-Gly and Gly-Cys as sulphur sources and cysteine precursors. A panel of C. jejuni mutants in putative peptidases and peptide transporters were generated and tested for their participation in the catabolism of the cysteine-containing peptides, and the predicted transporter protein CJJ81176_0236 was discovered to facilitate the growth with the dipeptide Cys-Gly, Ile-Arg and Ile-Trp. It was named Campylobacter peptide transporter A (CptA) and is the first representative of the oligopeptide transporter OPT family demonstrated to participate in the glutathione-derivative Cys-Gly catabolism in prokaryotes. Our study provides new insights into how host- and microbiota-derived substrates like sulphide, thiosulphate and short peptides are used by C. jejuni to compensate its restricted metabolic capacities.