| First Author | Poon IK | Year | 2014 |
| Journal | Nature | Volume | 507 |
| Issue | 7492 | Pages | 329-34 |
| PubMed ID | 24646995 | Mgi Jnum | J:208888 |
| Mgi Id | MGI:5565150 | Doi | 10.1038/nature13147 |
| Citation | Poon IK, et al. (2014) Unexpected link between an antibiotic, pannexin channels and apoptosis. Nature 507(7492):329-34 |
| abstractText | 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. |
