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 Mg(2+) medium. A link between these two phenotypes has been proposed due to putative Mg(2+) 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 Mg(2+). MgtC homologues from diverse gamma-proteobacteria, including the extracellular pathogens Yersinia pestis, Photorhabdus luminescens and Pseudomonas aeruginosa, have been expressed in a SalmonellaDeltamgtC strain. The Y. pestis MgtC fully replaced the Salmonella MgtC whereas P. luminescens or P. aeruginosa MgtC complemented only in low Mg(2+) 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 Mg(2+) culture. A SalmonellaDeltamgtC strain showed elongated and autoaggregated bacteria in low Mg(2+) medium but not in macrophages. Taken together our results suggest that MgtC has a dual role when bacteria localize in macrophages or low Mg(2+) environment.
Rang
Cécile
C
INSERM U431, Avenir Team, Faculté de Médecine, Avenue J. F. Kennedy, 30908 Nîmes Cedex 02, France.
Alix
Eric
E
Felix
Christine
C
Heitz
Annie
A
Tasse
Lena
L
Blanc-Potard
Anne-Béatrice
AB
D019943:Amino Acid Substitution; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D027682:Cation Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000737:chemistry; D017353:Gene Deletion; D005816:Genetic Complementation Test; D008264:Macrophages / Q000382:microbiology; D008274:Magnesium / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D016297:Mutagenesis, Site-Directed; D020637:Photorhabdus / Q000235:genetics; D017434:Protein Structure, Tertiary; D011550:Pseudomonas aeruginosa / Q000235:genetics; D012486:Salmonella typhimurium / Q000166:cytology / Q000235:genetics* / Q000472:pathogenicity*; D037521:Virulence Factors / Q000235:genetics / Q000502:physiology*; D015010:Yersinia pestis / Q000235:genetics
D001426:Bacterial Proteins; D027682:Cation Transport Proteins; D037521:Virulence Factors; C093586:MgtC protein, Salmonella typhimurium; D008274:Magnesium