Dual role of the MgtC virulence factor in host and non-host environments

MgtC is required for intramacrophage replication of intracellular pathogens and growth in low Mg2+ medium. A link between these two phenotypes has been proposed due to putative Mg2+ deprivation inside phagosome. MgtC is part of a family of proteins that share a conserved N-terminal transmembrane domain and a variable C-terminal domain. A combination of predictive and experimental approaches indicates that the Salmonella MgtC C-terminal domain is cytoplasmic, adopts a fold also found in metal transporters and RNA interacting domain, and does not bind Mg2+. MgtC homologues from diverse gamma-proteobacteria, including the extracellular pathogens Yersinia pestis, Photorhabdus luminescens and Pseudomonas aeruginosa, have been expressed in a Salmonella Delta mgtC strain. The Y. pestis MgtC fully replaced the Salmonella MgtC whereas P. luminescens or P. aeruginosa MgtC complemented only in low Mg2+ medium, thus dissociating for the first time the two MgtC-related phenotypes. In addition, we identified single amino acids changes that prevent or promote MgtC role in macrophages without affecting MgtC role in low Mg2+ culture. A Salmonella Delta mgtC strain showed elongated and autoaggregated bacteria in low Mg2+ medium but not in macrophages. Taken together our results suggest that MgtC has a dual role when bacteria localize in macrophages or low Mg2+ environment.