Polyphosphate kinase is involved in stress‐induced <i>mprAB‐sigE‐rel</i> signalling in mycobacteria

<jats:title>Summary</jats:title><jats:p>Polyphosphate kinase 1 (PPK1) helps bacteria to survive under stress. The <jats:italic>ppk1</jats:italic> gene of <jats:italic>Mycobacterium tuberculosis</jats:italic> was overexpressed in <jats:italic>Escherichia coli</jats:italic> 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 <jats:italic>ppk1</jats:italic> knockout mutant of <jats:italic>Mycobacterium smegmatis</jats:italic> was compromised in its ability to survive under long‐term hypoxia. The transcription of the <jats:italic>rel</jats:italic> gene and the synthesis of the stringent response regulator ppGpp were impaired in the mutant and restored after complementation with <jats:italic>ppk1</jats:italic> of <jats:italic>M. tuberculosis</jats:italic>, providing evidence that PPK1 is required for the stringent response. We present evidence that PPK1 is likely required for <jats:italic>mprAB‐sigE‐rel</jats:italic> signalling. σ<jats:sup>E</jats:sup> regulates the transcription of <jats:italic>rel</jats:italic>, and we hypothesize that under conditions of stress polyP acts as a preferred donor for MprB‐mediated phosphorylation of MprA facilitating transcription of the <jats:italic>sigE</jats:italic> gene thereby leading finally to the enhancement of the transcription of <jats:italic>rel</jats:italic> in <jats:italic>M. smegmatis</jats:italic> and <jats:italic>M. tuberculosis</jats:italic>. Downregulation of <jats:italic>ppk1</jats:italic> led to impaired survival of <jats:italic>M. tuberculosis</jats:italic> in macrophages. PolyP plays a central role in the stress response of mycobacteria.</jats:p>