论文标题

具有突变和水平基因转移的宿主内细菌生长动力学

Within-host bacterial growth dynamics with both mutation and horizontal gene transfer

论文作者

Djidjou-Demasse, Ramsès, Alizon, Samuel, Sofonea, Mircea T.

论文摘要

抗生素抗性的进化和出现是一个主要的公共卫生问题。对结合突变过程,水平基因转移和资源消耗结合的宿主内部微生物动力学的理解是解决此问题的关键之一。我们分析了一个通用模型,以严格描述四种细菌菌株的相互作用动力学:一种完全敏感的药物,一种仅具有突变耐药性,一种仅具有质粒抗性,一个具有两个抗性。通过否认阈值数(即每个菌株的效率繁殖和每个菌株的过渡阈值数字),我们是存在非琐碎固定状态的第一个表达条件。我们认为这些阈值主要取决于细菌的定量性状,例如养分消耗能力,生长转化因子,死亡率,突变(正向或反向)以及质粒概率的隔离损失(对于质粒的链条)。接下来,关于菌株的繁殖阈值数字中的顺序,我们表明该模型的定性动力学范围从所有菌株的灭绝,敏感和突变抗性菌株的共存到平衡处所有菌株的共存。最后,根据细菌菌株是没有药物作用(细胞抑制剂还是细胞毒性),我们经过一般分析的某些应用。

The evolution and emergence of antibiotic resistance is a major public health concern. The understanding of the within-host microbial dynamics combining mutational processes, horizontal gene transfer and resource consumption, is one of the keys to solve this problem. We analyze a generic model to rigorously describe interactions dynamics of four bacterial strains: one fully sensitive to the drug, one with mutational resistance only, one with plasmidic resistance only and one with both resistances. By dening thresholds numbers (i.e. each strain's eective reproduction and each strain's transition thresholds numbers), we rst express conditions for the existence of non trivial stationary states. We nd that these thresholds mainly depend on bacteria quantitative traits such as nutrient consumption ability, growth conversion factor, death rate, mutation (forward or reverse) and segregational loss of plasmid probabilities (for plasmid-bearing strains). Next, with respect to the order in the set of strain's eective reproduction thresholds numbers, we show that the qualitative dynamics of the model range from the extinction of all strains, coexistence of sensitive and mutational resistance strains to the coexistence of all strains at equilibrium. Finally, we go through some applications of our general analysis depending on whether bacteria strains interact without or with drug action (either cytostatic or cytotoxic).

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