title: Polyphosphate kinase is involved in stress-induced mprAB-sigE-rel signalling in mycobacteria.
abstract: Polyphosphate kinase 1 (PPK1) helps bacteria to survive under stress. The ppk1 gene of Mycobacterium tuberculosis was overexpressed in Escherichia coli and characterized. Residues R230 and F176, predicted to be present in the head domain of PPK1, were identified as residues critical for polyphosphate (polyP)-synthesizing ability and dimerization of PPK1. A ppk1 knockout mutant of Mycobacterium smegmatis was compromised in its ability to survive under long-term hypoxia. The transcription of the rel gene and the synthesis of the stringent response regulator ppGpp were impaired in the mutant and restored after complementation with ppk1 of M. tuberculosis, providing evidence that PPK1 is required for the stringent response. We present evidence that PPK1 is likely required for mprAB-sigE-rel signalling. sigma(E) regulates the transcription of rel, and we hypothesize that under conditions of stress polyP acts as a preferred donor for MprB-mediated phosphorylation of MprA facilitating transcription of the sigE gene thereby leading finally to the enhancement of the transcription of rel in M. smegmatis and M. tuberculosis. Downregulation of ppk1 led to impaired survival of M. tuberculosis in macrophages. PolyP plays a central role in the stress response of mycobacteria.
authors.affiliation: Department of Chemistry, Bose Institute, 93/1 Acharya Prafulla Chandra Road, Calcutta 700009, India.
authors.forename: Kamakshi
authors.initials: K
authors.lastname: Sureka
authors.forename: Supratim
authors.initials: S
authors.lastname: Dey
authors.forename: Pratik
authors.initials: P
authors.lastname: Datta
authors.forename: Anil Kumar
authors.initials: AK
authors.lastname: Singh
authors.forename: Arunava
authors.initials: A
authors.lastname: Dasgupta
authors.forename: Sébastien
authors.initials: S
authors.lastname: Rodrigue
authors.forename: Joyoti
authors.initials: J
authors.lastname: Basu
authors.forename: Manikuntala
authors.initials: M
authors.lastname: Kundu
mesh_terms: D000693:Anaerobiosis / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D004926:Escherichia coli / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D008025:Ligases / Q000235:genetics / Q000378:metabolism*; D020102:Mycobacterium smegmatis / Q000201:enzymology; D009169:Mycobacterium tuberculosis / Q000201:enzymology* / Q000235:genetics; D018384:Oxidative Stress; D017856:Phosphotransferases (Phosphate Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D017354:Point Mutation; D011122:Polyphosphates / Q000378:metabolism*; D012808:Sigma Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D001426:Bacterial Proteins; C480224:MprA protein, Mycobacterium tuberculosis; D011122:Polyphosphates; D012808:Sigma Factor; C111259:sigE protein, Bacteria; D017856:Phosphotransferases (Phosphate Group Acceptor); C022424:polyphosphate kinase; D008025:Ligases; C028812:guanosine 3',5'-polyphosphate synthetases