Xue Wenzhi, Hong Juken, Zhao Runmeng, Yao Huaxiong, Zhang Yi, Dai Zhuojun, Wang Teng
Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
School of Mathematics, Jilin University, Changchun, 130012, China.
Mol Syst Biol. 2025 Apr 29. doi: 10.1038/s44320-025-00110-8.
The dissemination of transferable plasmids, a major type of mobile genetic elements (MGEs), is one main driver of antibiotic resistance outbreaks. While the plasmid persistence condition in well-mixed environments has been extensively studied, most microbiota in nature are spatially heterogeneous. However, our knowledge regarding how spatial landscape shapes plasmid maintenance and dissemination remains limited. Here we establish a theoretical framework describing plasmid spread over a metacommunity of multiple patches. By analyzing the gene flow dynamics on randomly generated landscapes, we show that plasmid survival and dispersal are dictated by a simple feature of the landscape, spatial entropy. Reducing entropy speeds up plasmid range expansion and allows the global maintenance of many plasmids that are predicted to be lost by classic theories. The entropy's effects are experimentally validated in E. coli metacommunities transferring a conjugative plasmid. We further examine a vast collection of prokaryotic genomes and show that prokaryotes from low-entropy environments indeed carry more abundant MGEs and antibiotic resistance genes. Our work provides critical insights into the management and control of antimicrobial resistance.
可转移质粒作为移动遗传元件（MGEs）的一种主要类型，其传播是抗生素耐药性爆发的一个主要驱动因素。虽然在充分混合的环境中质粒的存续条件已得到广泛研究，但自然界中的大多数微生物群落都是空间异质的。然而，我们对于空间格局如何塑造质粒的维持和传播的了解仍然有限。在此，我们建立了一个理论框架，描述质粒在多个斑块的集合群落中的传播。通过分析随机生成的景观上的基因流动动态，我们发现质粒的存活和扩散由景观的一个简单特征——空间熵决定。降低熵会加速质粒的范围扩展，并能使许多预计会因经典理论而丢失的质粒在全球范围内得以维持。熵的影响在转移接合性质粒的大肠杆菌集合群落中得到了实验验证。我们进一步研究了大量原核生物基因组，并表明来自低熵环境的原核生物确实携带更丰富的移动遗传元件和抗生素耐药基因。我们的工作为抗微生物耐药性的管理和控制提供了关键见解。
