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. 2017 Mar 16;41(3):343–353. doi: 10.1093/femsre/fux006

Figure 3.

Figure 3.

(p)ppGpp-hipA mediated persister pathway. In response to particular stresses, SpoT and RelA are activated to synthesise the nucleotide alarmone (p)ppGpp, The increased (p)ppGpp levels lead to the accumulation of inoganic polyphosphate (PolyP) through inhibition of exopolyphosphatase (PPX), that the cellular enzyme to degrades PolyP. The accumulated PolyP combines with Lon protease preferentially to cleave the antitoxin HipB, resulting in an excess of toxin HipA. In return, free active toxin HipA inactivates GltX by phosphorylation of its ATP-binding site Ser239, with the consequence of uncharged tRNA with glutamate (tRNAGlu) accumulation in the cell. Uncharged tRNAGlu loads at empty ribosomal sites and triggers the activation of RelA to more (p)ppGpp synthesis, promoting cells entry into dormant state. Note that SpoT and RelA are bifunctional synthetase-hydrolase enzyme, if the stresses have been removed, they can hydrolase (p)ppGpp and bring cells to normal growth (Dalebroux and Swanson 2012). The red box labelled with ‘?’ indicates that the link between stringent response-associated genes (including ppGpp, Lon, PolyP) and TAs has been exploring in some TAs, such as relBE, mazEF and yefM-yeoB. It has been proved that the activation of toxin MazF and YoeB is dependent on the Lon-mediated degradation of their cognates, antitoxins, but not on the accumulation of PolyP and ppGpp (Christensen et al. 2001, 2003; Ramisetty et al. 2016).