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Updated: May 2, 2026

Evaluation of Caspase Activation to Assess Innate Immune Cell Death
Published on: January 20, 2023
Unexpected link between an antibiotic, pannexin channels and apoptosis
Ivan K H Poon1, Yu-Hsin Chiu2, Allison J Armstrong3
11] The Center for Cell Clearance, University of Virginia, Charlottesville, Virginia 22908, USA [2] Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, Virginia 22908, USA [3] Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, Virginia 22908, USA [4] La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria 3086, Australia.
Abstract:
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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