Institute of Molecular Biology, University of Oregon, Eugene, OR 97403.
Department of Physics, University of Oregon, Eugene, OR 97403.
Proc Natl Acad Sci U S A. 2019 Oct 22;116(43):21392-21400. doi: 10.1073/pnas.1907567116. Epub 2019 Oct 7.
Antibiotics induce large and highly variable changes in the intestinal microbiome even at sublethal concentrations, through mechanisms that remain elusive. Using gnotobiotic zebrafish, which allow high-resolution examination of microbial dynamics, we found that sublethal doses of the common antibiotic ciprofloxacin cause severe drops in bacterial abundance. Contrary to conventional views of antimicrobial tolerance, disruption was more pronounced for slow-growing, aggregated bacteria than for fast-growing, planktonic species. Live imaging revealed that antibiotic treatment promoted bacterial aggregation and increased susceptibility to intestinal expulsion. Intestinal mechanics therefore amplify the effects of antibiotics on resident bacteria. Microbial dynamics are captured by a biophysical model that connects antibiotic-induced collapses to gelation phase transitions in soft materials, providing a framework for predicting the impact of antibiotics on the intestinal microbiome.
抗生素即使在亚致死浓度下也会通过尚未阐明的机制，引起肠道微生物组的大幅且高度变化。使用无菌斑马鱼，我们可以对微生物动态进行高分辨率检查，发现亚致死剂量的常见抗生素环丙沙星会导致细菌丰度严重下降。与传统的抗菌药物耐受性观点相反，对于生长缓慢、聚集的细菌，其破坏作用比生长迅速、浮游的物种更为明显。活体成像显示，抗生素处理促进了细菌的聚集，并增加了对肠道排出的敏感性。因此，肠道力学放大了抗生素对常驻细菌的影响。微生物动态由一个生物物理模型捕获，该模型将抗生素诱导的崩溃与软物质中的凝胶化相变联系起来，为预测抗生素对肠道微生物组的影响提供了一个框架。
