Dybowski Richard, Restif Olivier, Goupy Alexandre, Maskell Duncan J, Mastroeni Piero, Grant Andrew J
Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, UK.
Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, UK ENSTA-ParisTech, 828 Boulevard des Maréchaux, Palaiseau 91120, France.
J R Soc Interface. 2015 Dec 6;12(113):20150702. doi: 10.1098/rsif.2015.0702.
Intravenous inoculation of Salmonella enterica serovar Typhimurium into mice is a prime experimental model of invasive salmonellosis. The use of wild-type isogenic tagged strains (WITS) in this system has revealed that bacteria undergo independent bottlenecks in the liver and spleen before establishing a systemic infection. We recently showed that those bacteria that survived the bottleneck exhibited enhanced growth when transferred to naive mice. In this study, we set out to disentangle the components of this in vivo adaptation by inoculating mice with WITS grown either in vitro or in vivo. We developed an original method to estimate the replication and killing rates of bacteria from experimental data, which involved solving the probability-generating function of a non-homogeneous birth-death-immigration process. This revealed a low initial mortality in bacteria obtained from a donor animal. Next, an analysis of WITS distributions in the livers and spleens of recipient animals indicated that in vivo-passaged bacteria started spreading between organs earlier than in vitro-grown bacteria. These results further our understanding of the influence of passage in a host on the fitness and virulence of Salmonella enterica and represent an advance in the power of investigation on the patterns and mechanisms of host-pathogen interactions.
将肠炎沙门氏菌鼠伤寒血清型静脉接种到小鼠体内是侵袭性沙门氏菌病的主要实验模型。在该系统中使用野生型同基因标记菌株（WITS）已表明，细菌在建立全身感染之前在肝脏和脾脏中经历独立的瓶颈效应。我们最近表明，那些在瓶颈效应中存活下来的细菌转移到未感染的小鼠体内时生长增强。在本研究中，我们通过用体外或体内培养的WITS接种小鼠来着手剖析这种体内适应性的组成部分。我们开发了一种从实验数据估计细菌复制和杀灭率的原始方法，该方法涉及求解非齐次生灭迁移过程的概率生成函数。这揭示了从供体动物获得的细菌初始死亡率较低。接下来，对受体动物肝脏和脾脏中WITS分布的分析表明，体内传代的细菌比体外培养的细菌更早开始在器官之间传播。这些结果进一步加深了我们对宿主传代对肠炎沙门氏菌适应性和毒力影响的理解，并代表了在研究宿主-病原体相互作用模式和机制的能力方面取得的进展。
