Abstract
MgtC is a virulence factor involved in intramacrophage growth that has been reported in several intracellular pathogens, including Mycobacterium tuberculosis and Salmonella enterica serovar Typhimurium. MgtC participates also in adaptation to Mg2+ deprivation. Herein, we have constructed a mgtC mutant in Mycobacterium marinum to further investigate the role of MgtC in mycobacteria. We show that the M. marinum mgtC gene (Mma mgtC) is strongly induced upon Mg2+ deprivation and is required for optimal growth in Mg2+-deprived medium. The behaviour of the Mma mgtC mutant has been investigated in the Danio rerio infection model using a transgenic reporter zebrafish line that specifically labels neutrophils. Although the mgtC mutant is not attenuated in the zebrafish embryo model based on survival curves, our results indicate that phagocytosis by neutrophils is enhanced with the mgtC mutant compared to the wild-type strain following subcutaneous injection. Increased phagocytosis of the mutant strain is also observed ex vivo with the murine J774 macrophage cell line. On the other hand, no difference was found between the mgtC mutant and the wild-type strain in bacterial adhesion to macrophages and in the internalization into epithelial cells. Unlike the role reported for MgtC in other intracellular pathogens, Mma MgtC does not contribute significantly to intramacrophage replication. Taken together, these results indicate an unanticipated function of Mma MgtC at early step of infection within phagocytic cells. Hence, our results indicate that although the MgtC function is conserved among pathogens regarding adaptation to Mg2+ deprivation, its role towards phagocytic cells can differ, possibly in relation with the specific pathogen's lifestyles.
Highlights
MgtC is a virulence factor common to several intracellular pathogens [1]
Because MgtC is conserved between M. tuberculosis and Mycobacterium marinum, we aimed to address its role in M. marinum virulence, as well as its regulation by magnesium
The present results indicate that Mma mgtC transcription is strongly induced by magnesium deprivation and, unexpectedly, that Mma MgtC appears dispensable for intramacrophage replication but plays a role in phagocytosis, a phenotype first uncovered in zebrafish embryos
Summary
MgtC is a virulence factor common to several intracellular pathogens [1] It was first described in Salmonella enterica serovar Typhimurium Typhimurium) as required for intramacrophage multiplication and systemic infection in mice [2,3,4]. Later, it was described as a critical factor for the intramacrophage growth of Mycobacterium tuberculosis, Brucella suis, Yersinia pestis, Burkholderia cenocepacia and Salmonella enterica serovar Typhi [5,6,7,8,9]. Despite its importance in the virulence of various bacterial pathogens, the mechanism by which MgtC promotes intracellular growth remains unknown. Modulation of F-ATP synthase activity is proposed to drive the ability of MgtC to promote intramacrophage replication
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