西亚试剂：Unexpected link between an antibiotic， pannexin channels an

Unexpected link between an antibiotic， pannexin channels and apoptosis

Ivan K. H. Poon，  Yu-Hsin Chiu，  Allison J. Armstrong，  Jason M. Kinchen，  Ignacio J. Juncadella，  Douglas A. Bayliss  & Kodi S. Ravichandran

Plasma membrane pannexin 1 channels (PANX1) release nucleotide find-me signals from apoptotic cells to attract phagocytes. Here we show that the quinolone antibiotic trovafloxacin is a novel PANX1 inhibitor， by using a small-molecule screen. Although quinolones are widely used to treat bacterial infections， some quinolones have unexplained side effects， including deaths among children. PANX1 is a direct target of trovafloxacin at drug concentrations seen in human plasma， and its inhibition led to dysregulated fragmentation of apoptotic cells. Genetic loss of PANX1 phenocopied trovafloxacin effects， revealing a non-redundant role for pannexin channels in regulating cellular disassembly during apoptosis. Increase in drug-resistant bacteria worldwide and the dearth of new antibiotics is a major human health challenge. Comparing different quinolone antibiotics suggests that certain structural features may contribute to PANX1 blockade. These data identify a novel linkage between an antibiotic， pannexin channels and cellular integrity， and suggest that re-engineering certain quinolones might help develop newer antibacterials.

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