PERSISTER PATHWAY: Phosphorylation of GltX by the bacterial toxin HipA (1) blocks GltX from adding an amino acid to transfer RNA (tRNA) (2). Uncharged tRNAs clog up the protein synthesis machinery (3), which leads to the production of the alarmone guanosine pentaphosphate [(p)ppGpp], synthesized by RelA, (4) and the subsequent shut down of cellular activities.
The paper
E. Germain et al., “The molecular mechanism of bacterial persistence by HipA,” Molecular Cell, 52:248-54, 2013.
In any given colony of, say, one million bacterial cells, there are bound to be one or two individuals that will survive an onslaught of antibiotics. The phenomenon, first identified in the 1940s, is called bacterial persistence or multidrug tolerance. Unlike antibiotic resistance, which results from a genetic alteration that renders a bacterium invulnerable to particular drugs, persistence derives from a sort of cellular sleep. Normal cellular functions shut down, giving antibiotics—which typically target active processes, such as translation or transcription—nothing to attack.
Bacteria capable of persistence have dueling protein pairs—a toxin and an antitoxin. The toxin forces the cell into a dormant state, and the antitoxin ...
