Research ResourceMicrobiology

The kinases HipA and HipA7 phosphorylate different substrate pools in Escherichia coli to promote multidrug tolerance

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Sci. Signal.  11 Sep 2018:
Vol. 11, Issue 547, eaat5750
DOI: 10.1126/scisignal.aat5750

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Balancing bacterial growth with drug resistance

Within some bacterial populations, a subset of cells grows more slowly than the rest, which decreases the competitive fitness of these cells under favorable growth conditions but enables them to survive exposure to antibiotics. The kinase HipA is important for the survival of such Escherichia coli persister cells because it targets the glutamate-tRNA ligase GltX, thus halting translation and slowing cell growth. A variant of this kinase that is associated with some clinical isolates, HipA7, is more efficient than HipA in inducing persistence, although it is less effective at reducing cell growth. Through phosphoproteomic analyses, Semanjski et al. found that although both HipA and HipA7 targeted GltX, HipA also targeted additional substrates, which likely account for the potency of HipA in reducing cell growth and may explain why HipA7, despite being more effective at promoting persistence, is less toxic than HipA.