Antibiotic therapy has drastically reduced the mortality and sequelae of bacterial infections. From naturally occurring to chemically synthesized, different classes of antibiotics have been successfully used without detailed knowledge of how they affect bacterial dynamics in vivo. However, a proportion of patients receiving antimicrobial therapy develop recrudescent infections post-treatment. Relapsing infections are attributable to incomplete clearance of bacterial populations following antibiotic administration; the metabolic profile of this antibiotic-recalcitrant bacterial subpopulation, the spatio-temporal context of its emergence and the variance of antibiotic–bacterial interactions in vivo remain unclear. Here, we develop and apply a mechanistic mathematical model to data from a study comparing the effects of ciprofloxacin and ampicillin on the within-host dynamics of Salmonella enterica serovar Typhimurium in murine infections. Using the inferential capacity of our model, we show that the antibiotic-recalcitrant bacteria following ampicillin, but not ciprofloxacin, treatment belong to a non-replicating phenotype. Aligning with previous studies, we independently estimate that the lymphoid tissues and spleen are important reservoirs of non-replicating bacteria. Finally, we predict that post-treatment, the progenitors of the non-growing and growing bacterial populations replicate and die at different rates. Ultimately, the liver, spleen and mesenteric lymph nodes are all repopulated by progenitors of the previously non-growing phenotype in ampicillin-treated mice.

中文翻译：

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一项基于数据的数学模型研究，用于量化环丙沙星和氨苄青霉素对治疗和复发期间肠道沙门氏菌宿主内动态的影响

抗生素治疗大大降低了细菌感染的死亡率和后遗症。从天然存在到化学合成，不同类别的抗生素已被成功使用，而无需详细了解它们如何影响体内细菌动力学。然而，一部分接受抗微生物治疗的患者在治疗后会出现复发性感染。复发性感染可归因于抗生素给药后细菌群的不完全清除；这种抗生素顽固性细菌亚群的代谢特征、其出现的时空背景以及体内抗生素-细菌相互作用的变化仍不清楚。这里，我们开发了一个机械数学模型并将其应用于一项研究的数据，该研究比较了环丙沙星和氨苄青霉素对鼠感染中鼠伤寒沙门氏菌血清型鼠伤寒沙门氏菌的宿主内动力学的影响。使用我们模型的推论能力，我们表明氨苄西林而不是环丙沙星治疗后的抗生素顽固细菌属于非复制表型。与之前的研究一致，我们独立估计淋巴组织和脾脏是非复制细菌的重要储存库。最后，我们预测在处理后，未生长和生长的细菌种群的祖细胞以不同的速率复制和死亡。最终，肝脏，