Bhattacharyya Souvik, Walker David M, Harshey Rasika M
Department of Molecular Biosciences, University of Texas at Austin, Austin, TX, 78712, USA.
Nat Commun. 2020 Aug 19;11(1):4157. doi: 10.1038/s41467-020-17709-0.
Swarming is a form of collective bacterial motion enabled by flagella on the surface of semi-solid media. Swarming populations exhibit non-genetic or adaptive resistance to antibiotics, despite sustaining considerable cell death. Here, we show that antibiotic-induced death of a sub-population benefits the swarm by enhancing adaptive resistance in the surviving cells. Killed cells release a resistance-enhancing factor that we identify as AcrA, a periplasmic component of RND efflux pumps. The released AcrA interacts on the surface of live cells with an outer membrane component of the efflux pump, TolC, stimulating drug efflux and inducing expression of other efflux pumps. This phenomenon, which we call 'necrosignaling', exists in other Gram-negative and Gram-positive bacteria and displays species-specificity. Given that adaptive resistance is a known incubator for evolving genetic resistance, our findings might be clinically relevant to the rise of multidrug resistance.
群体游动是半固体培养基表面鞭毛驱动的一种细菌集体运动形式。群体游动菌群体对抗生素表现出非遗传性或适应性抗性，尽管会有大量细胞死亡。在此，我们表明抗生素诱导的亚群细胞死亡通过增强存活细胞的适应性抗性而使群体受益。死亡细胞释放一种抗性增强因子，我们鉴定其为AcrA，即RND外排泵的周质成分。释放的AcrA在活细胞表面与外排泵的外膜成分TolC相互作用，刺激药物外排并诱导其他外排泵的表达。我们将这种现象称为“坏死信号传导”，它存在于其他革兰氏阴性菌和革兰氏阳性菌中，并表现出物种特异性。鉴于适应性抗性是已知的遗传抗性进化温床，我们的发现可能在临床上与多重耐药性的产生相关。
