Sci. Signal., 20 January 2009
Microbiology Escape Artists
Science, AAAS, Cambridge CB2 1LQ, UK
Bacterial multidrug tolerance (MDT) is an increasingly alarming phenomenon caused by the inability of antibiotics to eradicate infections completely. Most antibiotics target rapidly dividing cells. MDT is caused by a small population of bacterial cells, called persisters, which somehow become dormant but then switch back to growth phase after antibiotic removal and resume the infection. The biochemical basis for persistence is unknown, but the Escherichia coli HipA (High Persistence A) protein has been identified as a bona fide persistence factor. Schumacher et al. studied the structural mechanisms behind HipA function. HipA is a Ser/Thr kinase that phosphorylates the essential translation factor EF-Tu, potentially halting translation and leading to cell stasis. The DNA-binding protein HipB, which neutralizes HipA, was found to do so by locking HipA into an inactive state and by sequestering it away from its EF-Tu target.
M. A. Schumacher, K. M. Piro, W. Xu, S. Hansen, K. Lewis, R. G. Brennan, Molecular mechanisms of HipA-mediated multidrug tolerance and its neutralization by HipB. Science 323, 396–401 (2009). [Abstract] [Full Text]
Citation: H. Pickersgill, Escape Artists. Sci. Signal. 2, ec24 (2009).
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