The Metallochaperone Encoding Gene Is Widely Distributed among Pathogenic spp. and Its Expression Is Increased under Acidic pH and within Macrophages.

Metallochaperones are essential proteins that insert metal ions or metal cofactors into specific enzymes, that after maturation will become metalloenzymes. One of the most studied metallochaperones is the nickel-binding protein HypA, involved in the maturation of nickel-dependent hydrogenases and ureases. HypA was previously described in the human pathogens and and was considered a key virulence factor in the latter. However, nothing is known about this metallochaperone in the species of the emerging pathogen genus . These bacteria are native inhabitants of aquatic environments, often associated with cases of diarrhea and wound infections. In this study, we performed an in silico study of the gene on 36 species genomes, which showed the presence of the gene in 69.4% (25/36) of the genomes. The similarity of HypA proteins with the orthologous protein ranged from 21-23%, while with that of it was 41-45%. However, despite this low percentage, HypA displays the conserved characteristic metal-binding domains found in the other pathogens. The transcriptional analysis enabled the determination of expression levels under acidic and alkaline conditions and after macrophage phagocytosis The transcriptional regulation of was found to be pH-dependent, showing upregulation at acidic pH. A higher upregulation occurred after macrophage infection. This is the first study that provided evidence that the HypA metallochaperone in might play a role in acid tolerance and in the defense against macrophages.