Ruan Chujin, Vinod Deepthi P, Johnson David R
Department of Environmental Microbiology, Swiss Federal Institute of Aquatic Science and Technology (Eawag), Dübendorf, Switzerland.
Department of Environmental Systems Science, Swiss Federal Institute of Technology (ETH), Zürich, Switzerland.
Nat Commun. 2025 Jul 1;16(1):5839. doi: 10.1038/s41467-025-61055-y.
The persistence of antibiotic resistant (AR) bacteria in the absence of antibiotic pressure raises a paradox regarding the fitness costs associated with antibiotic resistance. These fitness costs should slow the growth of AR bacteria and cause them to be displaced by faster-growing antibiotic sensitive (AS) counterparts. Yet, even in the absence of antibiotic pressure, slower-growing AR bacteria can persist for prolonged periods of time. Here, we demonstrate a mechanism that can explain this apparent paradox. We hypothesize that lytic phage can modulate bacterial spatial organization to facilitate the persistence of slower-growing AR bacteria. Using surface-associated growth experiments with the bacterium Escherichia coli in conjunction with individual-based computational simulations, we show that phage disproportionately lyse the faster-growing AS counterpart cells located at the biomass periphery via a peripheral kill-the-winner dynamic. This enables the slower-growing AR cells to persist even when they are susceptible to the same phage. This phage-mediated selection is accompanied by enhanced bacterial diversity, further emphasizing the role of phage in shaping the assembly and evolution of bacterial systems. The mechanism is potentially relevant for any antibiotic resistance genetic determinant and has tangible implications for the management of bacterial populations via phage therapy.
在没有抗生素压力的情况下，抗生素抗性（AR）细菌的持续存在引发了一个关于与抗生素抗性相关的适应性代价的悖论。这些适应性代价应该会减缓AR细菌的生长，并导致它们被生长更快的抗生素敏感（AS）同类细菌所取代。然而，即使在没有抗生素压力的情况下，生长较慢的AR细菌也能长期持续存在。在这里，我们展示了一种能够解释这一明显悖论的机制。我们假设裂解性噬菌体可以调节细菌的空间组织，以促进生长较慢的AR细菌的持续存在。通过对大肠杆菌进行表面相关生长实验，并结合基于个体的计算模拟，我们表明噬菌体通过一种外周“杀死赢家”动态，不成比例地裂解位于生物量外围的生长较快的AS同类细胞。这使得生长较慢的AR细胞即使在它们对同一噬菌体敏感时也能持续存在。这种噬菌体介导的选择伴随着细菌多样性的增加，进一步强调了噬菌体在塑造细菌系统的组装和进化中的作用。该机制可能与任何抗生素抗性遗传决定因素相关，并且对通过噬菌体疗法管理细菌群体具有实际意义。
