The dual nature of bacteriophage: growth-dependent predation and generalised transduction of antimicrobial resistance
The dual nature of bacteriophage: growth-dependent predation and generalised transduction of antimicrobial resistance
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噬菌体的双重性质：生长依赖性捕食和抗菌素耐药性的普遍转导
DOI：
10.1101/2021.07.24.453184
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Leclerc Q
中科院分区：
文献类型：
--
作者：
Leclerc Q
噬菌体（“噬菌体”）既是细菌的捕食者，也是细菌的进化驱动力，特别是通过广义转导促进抗菌素耐药性（AMR）基因的传播。我们目前对这种关系的双重性质的理解是有限的。我们使用跨学科方法来量化这些相互作用的动态如何导致多重耐药细菌的进化。我们共培养了两株耐甲氧西林金黄色葡萄球菌，每株都带有不同的抗生素抗性基因，并带有 80α 通用转导噬菌体。 8小时的生长期后，细菌和噬菌体令人惊讶地在我们的培养物中以稳定平衡共存，其水平取决于噬菌体的起始浓度。我们早在7小时就检测到了双抗细菌，表明AMR基因的转导已经发生。我们开发了细菌和噬菌体关系的多个数学模型，并发现噬菌体-细菌动力学最好通过一个模型来捕获，其中噬菌体爆发大小随着细菌种群达到稳定期而减小，并且噬菌体捕食是频率依赖性的。我们估计，每 108 个新产生的噬菌体中就有一个是携带 AMR 基因的转导噬菌体，并且双抗细菌总是主要通过转导而不是生长产生。我们的结果表明我们理解和模拟噬菌体-细菌动力学的方式发生了转变。尽管普遍转导率可能被解释为太罕见而不显着，但它们足以持续导致多重耐药细菌的进化。目前，噬菌体造成日益严重的抗菌素耐药性负担的潜力可能被低估了。
Bacteriophage (“phage”) are both predators and evolutionary drivers for bacteria, notably contributing to the spread of antimicrobial resistance (AMR) genes by generalised transduction. Our current understanding of the dual nature of this relationship is limited. We used an interdisciplinary approach to quantify how these interacting dynamics can lead to the evolution of multi-drug resistant bacteria. We co-cultured two strains of Methicillin-resistantStaphylococcus aureus, each harbouring a different antibiotic resistance gene, with 80α generalized transducing phage. After a growth phase of 8h, bacteria and phage surprisingly coexisted at a stable equilibrium in our culture, the level of which was dependent on the starting concentration of phage. We detected double-resistant bacteria as early as 7h, indicating that transduction of AMR genes had occurred. We developed multiple mathematical models of the bacteria and phage relationship, and found that phage-bacteria dynamics were best captured by a model in which the phage burst size decreases as the bacteria population reaches stationary phase, and where phage predation is frequency-dependent. We estimated that one in every 108new phage generated was a transducing phage carrying an AMR gene, and that double-resistant bacteria were always predominantly generated by transduction rather than by growth. Our results suggest a shift in how we understand and model phage-bacteria dynamics. Although rates of generalised transduction could be interpreted as too rare to be significant, they are sufficient to consistently lead to the evolution of multi-drug resistant bacteria. Currently, the potential of phage to contribute to the growing burden of AMR is likely underestimated.
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