“富者愈富”机制驱动抗生素处理细菌的斑块动态和耐药性进化。

A 'rich-get-richer' mechanism drives patchy dynamics and resistance evolution in antibiotic-treated bacteria.

机构信息

Department of Biomedical Engineering, Duke University, Durham, NC, 27708, USA.

Center for Quantitative Biodesign, Duke University, Durham, NC, 27708, USA.

出版信息

Mol Syst Biol. 2024 Aug;20(8):880-897. doi: 10.1038/s44320-024-00046-5. Epub 2024 Jun 14.

Abstract

Bacteria in nature often form surface-attached communities that initially comprise distinct subpopulations, or patches. For pathogens, these patches can form at infection sites, persist during antibiotic treatment, and develop into mature biofilms. Evidence suggests that patches can emerge due to heterogeneity in the growth environment and bacterial seeding, as well as cell-cell signaling. However, it is unclear how these factors contribute to patch formation and how patch formation might affect bacterial survival and evolution. Here, we demonstrate that a 'rich-get-richer' mechanism drives patch formation in bacteria exhibiting collective survival (CS) during antibiotic treatment. Modeling predicts that the seeding heterogeneity of these bacteria is amplified by local CS and global resource competition, leading to patch formation. Increasing the dose of a non-eradicating antibiotic treatment increases the degree of patchiness. Experimentally, we first demonstrated the mechanism using engineered Escherichia coli and then demonstrated its applicability to a pathogen, Pseudomonas aeruginosa. We further showed that the formation of P. aeruginosa patches promoted the evolution of antibiotic resistance. Our work provides new insights into population dynamics and resistance evolution during surface-attached bacterial growth.

摘要

自然界中的细菌通常会形成表面附着的群落,最初由不同的亚群或斑块组成。对于病原体来说,这些斑块可以在感染部位形成,在抗生素治疗期间持续存在,并发展成成熟的生物膜。有证据表明,斑块的形成可能是由于生长环境和细菌接种的异质性以及细胞间信号传递所致。然而,目前尚不清楚这些因素如何促成斑块的形成,以及斑块的形成如何影响细菌的生存和进化。在这里,我们证明了一种“富者愈富”的机制驱动了在抗生素治疗期间表现出群体生存(CS)的细菌中的斑块形成。模型预测,这些细菌的播种异质性会被局部 CS 和全球资源竞争放大,导致斑块的形成。增加非杀菌性抗生素治疗剂量会增加斑块形成的程度。实验上,我们首先使用工程化的大肠杆菌证明了该机制,然后证明了它在病原体铜绿假单胞菌中的适用性。我们进一步表明,铜绿假单胞菌斑块的形成促进了抗生素耐药性的进化。我们的工作为表面附着细菌生长过程中的种群动态和耐药性进化提供了新的见解。

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