Shuppara Alexander M, Padron Gilberto C, Sharma Anuradha, Modi Zil, Koch Matthias D, Sanfilippo Joseph E
Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Department of Biology, Texas A&M University, College Station, TX 77843, USA.
Sci Adv. 2025 Mar 14;11(11):eads5005. doi: 10.1126/sciadv.ads5005. Epub 2025 Mar 12.
Bacterial populations experience chemical gradients in nature. However, most experimental systems either ignore gradients or fail to capture gradients in mechanically relevant contexts. Here, we use microfluidic experiments and biophysical simulations to explore how host-relevant shear flow affects antimicrobial gradients across communities of the highly resistant pathogen . We discover that flow patterns gradients of three chemically distinct antimicrobials: hydrogen peroxide, gentamicin, and carbenicillin. Without flow, resistant cells generate local gradients by neutralizing all three antimicrobials through degradation or chemical modification. As flow increases, delivery overwhelms neutralization, allowing antimicrobials to penetrate deeper into bacterial populations. By imaging single cells across long microfluidic channels, we observe that upstream cells protect downstream cells, and protection is abolished in higher flow regimes. Together, our results reveal that physical flow can promote antimicrobial effectiveness, which could inspire the incorporation of flow into the discovery, development, and implementation of antimicrobials.
细菌群体在自然环境中会经历化学梯度。然而，大多数实验系统要么忽略梯度，要么无法在与机械相关的环境中捕捉到梯度。在这里，我们使用微流体实验和生物物理模拟来探索与宿主相关的剪切流如何影响高抗性病原体群落中的抗菌梯度。我们发现流动模式会影响三种化学性质不同的抗菌剂的梯度：过氧化氢、庆大霉素和羧苄青霉素。在没有流动的情况下，抗性细胞通过降解或化学修饰中和所有三种抗菌剂来产生局部梯度。随着流量增加，输送超过中和作用，使抗菌剂能够更深入地渗透到细菌群体中。通过对长微流体通道中的单个细胞进行成像，我们观察到上游细胞保护下游细胞，而在更高的流动状态下这种保护作用消失。总之，我们的结果表明物理流动可以提高抗菌效果，这可能会促使在抗菌剂的发现、开发和应用中纳入流动因素。
