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报道：来自瑞士巴塞尔大学生物研究中心－重点领域感染生物学实验室的Dirk Bumann教授及其合作实验室发现了沙门氏菌在增殖方面的表型差异将导致其对抑菌化学疗法的耐受性，这篇文章刊登在最新一期2014年8月14日的《Cell》杂志上。
中文翻译
【题目】宿主组织中沙门氏菌的表型差异可延迟抑菌化疗的根除效果
【要点】TIMER是在感染的宿主组织中反应病原体单细胞生长速率的报告基因；沙门氏菌中具有不同生长速率的亚型在感染的小鼠脾脏中共存；抑菌化学疗法主要清除生长速率较快的沙门氏菌；大量生长速率适中的沙门氏菌的耐药性会延缓根除效果
【译文】抗生素疗法很多时候并不能清除小部分具有瞬时耐药性的细菌，这些菌群将会导致病情反复以及慢性感染的发生。在体外实验中发现了许多能够诱导高度耐药性细菌产生的机制，但它们在体内的相关机制尚不明确。本组应用了一种可测定生长速率的荧光报告基因，检测到在宿主组织中的沙门氏菌具有大量不同的生长表型。其中包括慢速生长的亚型以及在营养充足时快速生长并且致病的亚型。通过检测在化学疗法条件下沙门氏菌的生长速率，我们发现抗生素的杀菌效果与单细胞分裂速度密切相关。不分裂的沙门氏菌的存活度最高，但由于其数量很少，所以并不能影响致病进程。绝大多数存活下来的菌群反而来自于大量生长速率适中，且具备一定耐药性的沙门氏菌。这些实验结果说明了宿主组织存在病原体的生理学多样性，这对疾病的进程以及病情的控制起到关键作用。
英文原稿
[Title] Phenotypic Variation of Salmonella in Host Tissues Delays Eradication by Antimicrobial Chemotherapy
[Authors] Beatrice Claudi, Petra Spröte, Anna Chirkova, Nicolas Personnic, Janine Zankl, Nura Schürmann, Alexander Schmidt, Dirk Bumann
[Highlights] TIMER is a single-cell growth rate reporter for pathogens in infected host tissues.
Salmonella subsets with divergent growth rates coexist in infected mouse spleen.
Antimicrobial chemotherapy kills predominantly fast-growing Salmonella.
Partial tolerance of abundant moderately growing Salmonella delays eradication.
[Summary] Antibiotic therapy often fails to eliminate a fraction of transiently refractory bacteria, causing relapses and chronic infections.
Multiple mechanisms can induce such persisters with high antimicrobial tolerance in vitro, but their in vivo relevance remains
unclear. Using a fluorescent growth rate reporter, we detected extensive phenotypic variation of Salmonella in host tissues.
This included slow-growing subsets as well as well-nourished fast-growing subsets driving disease progression. Monitoring
of Salmonella growth and survival during chemotherapy revealed that antibiotic killing correlated with single-cell division rates.
Nondividing Salmonella survived best but were rare, limiting their impact. Instead, most survivors originated from abundant
moderately growing, partially tolerant Salmonella. These data demonstrate that host tissues diversify pathogen physiology,
with major consequences for disease progression and control.
原文地址：http://www.cell.com/cell/abstract/S0092-8674%2814%2900872-1
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