Mutation on lysX from Mycobacterium avium hominissuis impacts the host–pathogen interaction and virulence phenotype

ABSTRACT

The lysX gene from Mycobacterium avium hominissuis (MAH) is not only involved in cationic antimicrobial resistance but also regulates metabolic activity. An MAH lysX deficient mutant was shown to exhibit a metabolic shift at the extracellular state preadapting the bacteria to the conditions inside host-cells. It further showed stronger growth in human monocytes. In the present study, the LysX activity on host–pathogen interactions were analyzed. The lysX mutant from MAH proved to be more sensitive toward host-mediated stresses such as reactive oxygen species. Further, the lysX mutant exhibited increased inflammatory response in PBMC and multinucleated giant cell (MGC) formation in human macrophages during infection studies. Coincidentally, the lysX mutant strain revealed to be more reproductive in the Galleria mellonella infection model. Together, these data demonstrate that LysX plays a role in regulating the bacillary load in host organisms and the lack of lysX gene facilitates MAH adaptation to intracellular host-habitat, thereby suggesting an essential role of LysX in the modulation of host–pathogen interaction.

KEYWORDS:

• Virulence
• Mycobacterium avium hominissuis
• nontuberculous mycobacteria
• Galleria mellonella infection model
• multinucleated giant cells
• pathogenesis
• lysX (lysyl-tRNA synthetase)
• host-pathogen interaction
• inflammatory cytokines

Acknowledgments

We express our thanks to the animal facility of Robert Koch Institute (MF3 divison: Dr. Petra Kirsch, Annette Dietrich and Alice Stern) for providing the G. mellonella larvae for infection experiments, Christoph Schaudinn (Robert Koch Institute, Berlin) for his assistance and support in microscopy and Elisabeth Kamal and Barbara Kropp (Robert Koch Institute, Berlin) for excellent technical support. Greana Kirubakar was funded by the Rosa Luxemburg foundation, Georg & Agnes Blumenthal Stiftung and Richard-Winter-Stiftung.

Disclosure statement

No potential conflict of interest was reported by the authors.

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Funding

This work was supported by the Georg & Agnes Blumenthal Stiftung; Richard-Winter-Stiftung; Rosa Luxemburg Stiftung.