Department of Medical Chemistry, University of Szeged, Dóm tér 8, Szeged, Hungary.
Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre, National Laboratory of Biotechnology, Hungarian Research Network (HUN-REN), Szeged, Hungary.
Commun Biol. 2024 Oct 5;7(1):1264. doi: 10.1038/s42003-024-06946-4.
The negative membrane potential within bacterial cells is crucial in various essential cellular processes. Sustaining a hyperpolarised membrane could offer a novel strategy to combat antimicrobial resistance. However, it remains uncertain which molecules are responsible for inducing hyperpolarization and what the underlying molecular mechanisms are. Here, we demonstrate that chemically diverse antimicrobial peptides (AMPs) trigger hyperpolarization of the bacterial cytosolic membrane when applied at subinhibitory concentrations. Specifically, these AMPs adopt a membrane-induced amphipathic structure and, thereby, generate hyperpolarization in Escherichia coli without damaging the cell membrane. These AMPs act as selective ionophores for K (over Na) or Cl (over HPO and NO) ions, generating diffusion potential across the membrane. At lower dosages of AMPs, a quasi-steady-state membrane polarisation value is achieved. Our findings highlight the potential of AMPs as a valuable tool for chemically hyperpolarising bacteria, with implications for antimicrobial research and bacterial electrophysiology.
细菌细胞内的负膜电位在各种重要的细胞过程中至关重要。维持超极化的膜可能提供一种对抗抗菌药物耐药性的新策略。然而，目前尚不清楚哪些分子负责诱导超极化，以及潜在的分子机制是什么。在这里，我们证明了在亚抑菌浓度下，化学性质多样的抗菌肽 (AMPs) 可引发细菌细胞质膜的超极化。具体来说，这些 AMP 采用一种膜诱导的两亲性结构，从而在不破坏细胞膜的情况下使大肠杆菌发生超极化。这些 AMP 作为 K (相对于 Na) 或 Cl (相对于 HPO 和 NO) 离子的选择性离子载体，在膜两侧产生扩散电势。在较低剂量的 AMP 作用下，可达到准稳态膜极化值。我们的研究结果强调了 AMP 作为一种化学超极化细菌的有价值工具的潜力，这对抗菌药物研究和细菌电生理学具有重要意义。
