Correction for Leclerc et al., "Growth-Dependent Predation and Generalized Transduction of Antimicrobial Resistance by Bacteriophage".
Correction for Leclerc et al., "Growth-Dependent Predation and Generalized Transduction of Antimicrobial Resistance by Bacteriophage".
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DOI：
10.1128/msystems.00974-22
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发表时间：
2023-02-23
期刊：
影响因子：
6.4
通讯作者：
中科院分区：
文献类型：
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作者：
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。我们目前对这种复杂关系的理解是有限的。我们采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。我们共培养了两种耐甲氧西林金黄色葡萄球菌菌株，每种菌株都带有不同的抗生素抗性基因，并具有通用转导噬菌体。经过 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，发现噬菌体-细菌动力学最好通过一个模型来捕捉，在该模型中，随着细菌种群达到稳定期，噬菌体爆发大小减小，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。尽管广义转导率可能被解释为太罕见而不显着，但它们在我们的系统中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 AMR 负担的潜力可能被低估了。 重要性 噬菌体（噬菌体）是一种可以感染和杀死细菌的病毒，目前正在通过噬菌体疗法进行研究，作为应对抗菌素耐药性 (AMR) 威胁的潜在解决方案。然而实际上，当噬菌体意外地在细菌之间携带非噬菌体 DNA 时，它们也是细菌通过转导进化的自然驱动力。使用实验室工作和数学模型，我们表明转导导致多重耐药细菌在不到 8 小时内进化，并且当细菌生长减少时噬菌体产量减少，从而使细菌和噬菌体能够以稳定平衡共存。噬菌体捕食和转导的联合动态导致与细菌的复杂相互作用，必须澄清这一点，以防止噬菌体促进抗菌素耐药性的传播。
Bacteriophage (phage) are both predators and evolutionary drivers for bacteria, notably contributing to the spread of antimicrobial resistance (AMR) genes by generalized transduction. Our current understanding of this complex relationship is limited. We used an interdisciplinary approach to quantify how these interacting dynamics can lead to the evolution of multidrug-resistant bacteria. We cocultured two strains of methicillin-resistant Staphylococcus aureus, each harboring a different antibiotic resistance gene, with generalized transducing phage. After a growth phase of 8 h, 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 7 h, 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 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 generalized transduction could be interpreted as too rare to be significant, they are sufficient in our system to consistently lead to the evolution of multidrug-resistant bacteria. Currently, the potential of phage to contribute to the growing burden of AMR is likely underestimated.IMPORTANCEBacteriophage (phage), viruses that can infect and kill bacteria, are being investigated through phage therapy as a potential solution to the threat of antimicrobial resistance (AMR). In reality, however, phage are also natural drivers of bacterial evolution by transduction when they accidentally carry nonphage DNA between bacteria. Using laboratory work and mathematical models, we show that transduction leads to evolution of multidrug-resistant bacteria in less than 8 h and that phage production decreases when bacterial growth decreases, allowing bacteria and phage to coexist at stable equilibria. The joint dynamics of phage predation and transduction lead to complex interactions with bacteria, which must be clarified to prevent phage from contributing to the spread of AMR.
影响因子：
30.3
作者：
Roach, Dwayne R.;Leung, Chung Yin;Debarbieux, Laurent
通讯作者：
Debarbieux, Laurent