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<p><i>Acinetobacter baumannii</i> is a multidrug-resistant nosocomial pathogen responsible for infections that are often difficult to treat. Here, we show that exposure of <i>A. baumannii</i> to the last-resort antibiotic colistin, which disrupts the outer membrane of Gram-negative bacteria, results in inner membrane permeabilization and depolarization, ultimately inhibiting ATP synthesis. Nevertheless, under these conditions, colistin-resistant mutants are rapidly and frequently selected. In addition, <i>A. baumannii</i> is able to tolerate colistin, most likely due membrane depolarization and ATP depletion, which are hallmarks of antibiotic-tolerant subpopulations. In this context, we investigated whether bacteriocins can potentiate colistin activity. We identified and characterized two bacteriocins that inhibit the growth of multidrug-resistant clinical isolates, albeit at high concentrations. In vitro analyses showed that these small α-helical bacteriocins permeabilize phospholipid vesicles, highlighting their potential to potentiate antibiotics that compromise cell envelope integrity. Importantly, low concentrations of these bacteriocins combined with colistin leads to a substantial reduction in survival. Moreover, bacteriocin-colistin combinations limit the emergence of colistin-resistant mutants and partially restore susceptibility in colistin-resistant strains. These findings highlight the potential of combining bacteriocins and antibiotics to disrupt cell envelope homeostasis and support further evaluation of this strategy in vivo.</p><p></p>

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Combinations of colistin and bacteriocins prevent the selection of colistin resistance in Acinetobacter baumannii

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月14日

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  • Tristan Rubio,
  • Thomas zur Nedden,
  • Safia Zedek,
  • Dorothée Raoux-Bardot,
  • Calixte Cottineau,
  • Ludovic Belot,
  • Clément Raynaud,
  • Thierry Oms,
  • Hector Rodriguez-Vilallobos,
  • Dukas Jurenas,
  • Alexandre Chenal,
  • Laurence Van Melderen

摘要

Acinetobacter baumannii is a multidrug-resistant nosocomial pathogen responsible for infections that are often difficult to treat. Here, we show that exposure of A. baumannii to the last-resort antibiotic colistin, which disrupts the outer membrane of Gram-negative bacteria, results in inner membrane permeabilization and depolarization, ultimately inhibiting ATP synthesis. Nevertheless, under these conditions, colistin-resistant mutants are rapidly and frequently selected. In addition, A. baumannii is able to tolerate colistin, most likely due membrane depolarization and ATP depletion, which are hallmarks of antibiotic-tolerant subpopulations. In this context, we investigated whether bacteriocins can potentiate colistin activity. We identified and characterized two bacteriocins that inhibit the growth of multidrug-resistant clinical isolates, albeit at high concentrations. In vitro analyses showed that these small α-helical bacteriocins permeabilize phospholipid vesicles, highlighting their potential to potentiate antibiotics that compromise cell envelope integrity. Importantly, low concentrations of these bacteriocins combined with colistin leads to a substantial reduction in survival. Moreover, bacteriocin-colistin combinations limit the emergence of colistin-resistant mutants and partially restore susceptibility in colistin-resistant strains. These findings highlight the potential of combining bacteriocins and antibiotics to disrupt cell envelope homeostasis and support further evaluation of this strategy in vivo.