Growth-Dependent Predation and Generalized Transduction of Antimicrobial Resistance by Bacteriophage.
Growth-Dependent Predation and Generalized Transduction of Antimicrobial Resistance by Bacteriophage.
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生长依赖性噬菌体捕食和抗菌素耐药性的广义转导。
DOI：
10.1128/msystems.00135-22
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发表时间：
2022-04-26
期刊：
影响因子：
6.4
通讯作者：
中科院分区：
文献类型：
--
作者：
噬菌体既是细菌的捕食者，也是细菌进化的驱动者，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。我们使用跨学科的方法来量化这些相互作用的动力学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，每一个窝藏不同的抗生素耐药基因，与广义转导噬菌体。在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的平衡共存，其水平取决于噬菌体的起始浓度。我们早在7小时就检测到双耐药细菌，表明AMR基因的转导已经发生。我们开发了多个数学模型的细菌和噬菌体的关系，发现噬菌体-细菌动力学最好的捕捉模型中，噬菌体爆发的大小减少，细菌种群达到稳定期，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，并且双耐药细菌总是主要通过转导而不是生长产生。我们的研究结果表明，我们如何理解和模型噬菌体细菌动力学的转变。虽然广义转导率可能被解释为太罕见而不显着，但在我们的系统中，它们足以持续导致多重耐药细菌的进化。目前，噬菌体导致AMR负担日益加重的潜力可能被低估。重要性噬菌体（噬菌体），可以感染和杀死细菌的病毒，正在研究通过噬菌体治疗作为一个潜在的解决方案的威胁抗菌素耐药性（AMR）。然而，实际上，当噬菌体偶然在细菌之间携带非噬菌体DNA时，它们也是细菌进化的天然驱动力。使用实验室工作和数学模型，我们表明，转导导致多药耐药细菌的进化在不到8小时，噬菌体生产减少时，细菌生长减少，使细菌和噬菌体共存于稳定的平衡。噬菌体捕食和转导的联合动力学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AMR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 108 new 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. IMPORTANCE Bacteriophage (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.
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影响因子：
3.2
作者：
CHATTERJEE, AN
通讯作者：
CHATTERJEE, AN
影响因子：
6.4
作者：
Fey PD;Endres JL;Yajjala VK;Widhelm TJ;Boissy RJ;Bose JL;Bayles KW
通讯作者：
Bayles KW
影响因子：
4.8
作者：
Fišarová L;Botka T;Du X;Mašlaňová I;Bárdy P;Pantůček R;Benešík M;Roudnický P;Winstel V;Larsen J;Rosenstein R;Peschel A;Doškař J
通讯作者：
Doškař J
影响因子：
5.4
作者：
Kasman, LM;Kasman, A;Norris, JS
通讯作者：
Norris, JS
DOI：
10.1007/978-1-4939-7343-9_1
发表时间：
2018-01-01
期刊：
BACTERIOPHAGES, VOL. 3
影响因子：
--
作者：
Abedon, Stephen T.;Katsaounis, Tena I.
通讯作者：
Katsaounis, Tena I.