A Redox Regulatory System Critical for Mycobacterial Survival in Macrophages and Biofilm Development

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Nearly one-third of the world’s population is infected with Mycobacterium tuberculosis (Mtb), the causative agent of TB. A key factor that contributes to the widespread infection of Mtb is its capacity to survive inside the host macrophage. Understanding how Mtb withstands the hostile intracellular environment of this phagocytic cell may reveal targets for development of therapeutics that enhance the innate anti-Mtb activities of the macrophage. We discovered a novel signaling pathway in mycobacteria which regulates cellular redox homeostasis through NADH and FAD, regulators of metabolism and redox balance. NADH induces the expression of a protein kinase, PknG, which then phosphorylates the ribosomal protein L13 and promotes its presence in the cytoplasm. L13 therein forms a complex with RenU, a Nudix (Nucleoside diphosphate linked moiety X) hydrolase that degrades NADH and FAD. Genetic disruption of this signaling cascade leads to cellular accumulation of these molecules, increased mycobacterial sensitivity to oxidative stress, impaired surface biofilm growth, and most importantly, reduced survival of Mtb in macrophages.

Vyšlo v časopise: A Redox Regulatory System Critical for Mycobacterial Survival in Macrophages and Biofilm Development. PLoS Pathog 11(4): e32767. doi:10.1371/journal.ppat.1004839
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004839

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