Fast growth can counteract antibiotic susceptibility in shaping microbial community resilience to antibiotics.
Fast growth can counteract antibiotic susceptibility in shaping microbial community resilience to antibiotics.
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DOI：
10.1073/pnas.2116954119
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发表时间：
2022-04-12
影响因子：
11.1
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中科院分区：
文献类型：
--
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抗生素暴露是最常用的干预措施之一，可以使微生物群落远离不希望的状态。微生物群落的生态如何影响它们的恢复？在抗生素暴露后，治疗后转向肠道中的艰难梭菌感染尚不清楚。我们使用一个可以达到两种可选状态的模型社区来研究社区对抗生素的反应。在理论指导下，我们的实验表明，抗生素暴露后的微生物生长可以抵消抗生素敏感性，从而驱动不同群落状态之间的转变。这使得通过改变生长动态，包括社区成员的合作生长，扭转抗生素暴露的结果成为可能。我们的研究强调了简单生态模型的相关性，以更好地理解抗生素治疗的长期影响。微生物群落经常面临外部扰动，可导致其组成和功能的持久变化。我们对多物种群落如何应对诸如抗生素之类的扰动的理解是有限的，对个体、孤立物种进行的敏感性分析是预测群落转变的主要指南。在这里，我们研究了细菌生长动力学如何克服抗生素敏感性的差异，从而决定群落恢复力：抗生素暴露后原始群落状态的恢复。我们使用含有氨棒状杆菌和植物乳杆菌的实验群落，由于相互抑制，它们表现出两种可选的稳定状态。虽然单培养的C. amiagenes对氯霉素更敏感，但我们发现氯霉素暴露仍然导致L. plantarum为主的群落状态向C. amiagenes为主的群落状态过渡。结合理论和实验，我们证明了两个物种之间生长速度的差异使得植物乳杆菌为主的群落对几种作用机制不同的抗生素的适应性较差。利用观察到的合作-依赖于种群丰度-在C. am氨菌的生长中，我们接下来分析了可能损害C. am氨菌主导状态的高弹性的硅情景。该模型预测，通过与低种群密度的生长相互作用，降低扩散速率，可以使C.氨细菌对几乎任何一种抗生素都处于脆弱状态，我们通过实验证实了这一预测。我们的研究结果强调，由于抗生素暴露后的生长动态可能起主导作用，物种对抗生素的敏感性通常不能反映群落的恢复力。
Antibiotic exposure stands among the most used interventions to drive microbial communities away from undesired states. How the ecology of microbial communities shapes their recovery—e.g., posttreatment shifts toward Clostridioides difficile infections in the gut—after antibiotic exposure is poorly understood. We study community response to antibiotics using a model community that can reach two alternative states. Guided by theory, our experiments show that microbial growth following antibiotic exposure can counteract antibiotic susceptibility in driving transitions between alternative community states. This makes it possible to reverse the outcome of antibiotic exposure through modifying growth dynamics, including cooperative growth, of community members. Our research highlights the relevance of simple ecological models to better understand the long-term effects of antibiotic treatment. Microbial communities often face external perturbations that can induce lasting changes in their composition and functions. Our understanding of how multispecies communities respond to perturbations such as antibiotics is limited, with susceptibility assays performed on individual, isolated species our primary guide in predicting community transitions. Here, we studied how bacterial growth dynamics can overcome differences in antibiotic susceptibility in determining community resilience: the recovery of the original community state following antibiotic exposure. We used an experimental community containing Corynebacterium ammoniagenes and Lactobacillus plantarum that displays two alternative stable states as a result of mutual inhibition. Although C. ammoniagenes was more susceptible to chloramphenicol in monocultures, we found that chloramphenicol exposure nonetheless led to a transition from the L. plantarum-dominated to the C. ammoniagenes-dominated community state. Combining theory and experiments, we demonstrated that growth rate differences between the two species made the L. plantarum-dominated community less resilient to several antibiotics with different mechanisms of action. Taking advantage of an observed cooperativity—a dependence on population abundance—in the growth of C. ammoniagenes, we next analyzed in silico scenarios that could compromise the high resilience of the C. ammoniagenes-dominated state. The model predicted that lowering the dispersal rate, through interacting with the growth at low population densities, could make the C. ammoniagenes state fragile against virtually any kind of antibiotic, a prediction that we confirmed experimentally. Our results highlight that species susceptibility to antibiotics is often uninformative of community resilience, as growth dynamics in the wake of antibiotic exposure can play a dominant role.
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