title: PhoY2 of mycobacteria is required for metabolic homeostasis and stress response.
abstract: The ability of pathogenic mycobacteria to adapt to diverse environments is essential for their success as pathogens. Here we describe a transposon-inactivated phoY2 mutant of Mycobacterium marinum. PhoY2 of mycobacteria is a functional homologue of PhoU in Escherichia coli and an important component of the Pho regulon. We found that PhoY2 is required for maintaining intracellular inorganic phosphate (P(i)) homeostasis and balanced energy and redox states. Disruption of phoY2 resulted in elevated levels of intracellular poly-P(i) and ATP and an elevated NAD(+)/NADH ratio, and the mutant strain exhibited increased sensitivity to environmental stress conditions, including nutrient deprivation as well as SDS and antibiotic treatments. Taken together, our results suggest that PhoY2 is required for maintaining metabolic homeostasis and adaptation to stress conditions, which may provide an explanation for the suggested role of PhoY2 in drug tolerance.
authors.affiliation: Key Laboratory of Medical Molecular Virology, Institute of Biomedical Sciences and Institute of Medical Microbiology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Mao
authors.forename: Jia
authors.initials: J
authors.lastname: Yu
authors.forename: Lin
authors.initials: L
authors.lastname: Zhu
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.forename: Decheng
authors.initials: D
authors.lastname: Wang
authors.forename: Dandan
authors.initials: D
authors.lastname: Dong
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Qian
authors.initials: Q
authors.lastname: Gao
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D004251:DNA Transposable Elements; D004734:Energy Metabolism; D055786:Gene Knockout Techniques; D006706:Homeostasis; D016254:Mutagenesis, Insertional; D019910:Mycobacterium marinum / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009243:NAD / Q000378:metabolism; D010084:Oxidation-Reduction; D010710:Phosphates / Q000378:metabolism*; D013312:Stress, Physiological
chemical_list: D001426:Bacterial Proteins; D004251:DNA Transposable Elements; D010710:Phosphates; D009243:NAD; D000255:Adenosine Triphosphate