Physics of Living Systems, Department of Physics, Massachusetts Institute of Technology, Cambridge, MA, USA.
Physics of Living Systems, Department of Physics, Massachusetts Institute of Technology, Cambridge, MA, USA
Mol Syst Biol. 2019 Jun 11;15(6):e8707. doi: 10.15252/msb.20188707.
Quantifying virulence remains a central problem in human health, pest control, disease ecology, and evolutionary biology. Bacterial virulence is typically quantified by the (i.e., the time taken to kill 50% of infected hosts); however, such an indicator cannot account for the full complexity of the infection process, such as distinguishing between the pathogen's ability to colonize versus kill the hosts. Indeed, the pathogen needs to breach the primary defenses in order to colonize, find a suitable environment to replicate, and finally express the virulence factors that cause disease. Here, we show that two virulence attributes, namely pathogen lethality and invasiveness, can be disentangled from the survival curves of a laboratory population of nematodes exposed to three bacterial pathogens: , and We first show that the host population eventually experiences a constant mortality rate, which quantifies the lethality of the pathogen. We then show that the time necessary to reach this constant mortality rate regime depends on the pathogen growth rate and colonization rate, and thus determines the pathogen invasiveness. Our framework reveals that is particularly good at the initial colonization of the host, whereas is a poor colonizer yet just as lethal once established. , on the other hand, is both a good colonizer and highly lethal after becoming established. The ability to quantitatively characterize the ability of different pathogens to perform each of these steps has implications for treatment and prevention of disease and for the evolution and ecology of pathogens.
量化毒力仍然是人类健康、害虫控制、疾病生态学和进化生物学中的一个核心问题。细菌的毒力通常通过（即杀死 50%受感染宿主所需的时间）来量化；然而，这样的指标不能完全说明感染过程的复杂性，例如区分病原体定植与杀死宿主的能力。事实上，病原体需要突破主要防御才能定植，找到合适的环境进行复制，最后表达导致疾病的毒力因子。在这里，我们展示了两个毒力属性，即病原体致死率和侵袭性，可以从暴露于三种细菌病原体的实验室线虫种群的生存曲线中分离出来：、和。我们首先表明，宿主种群最终会经历一个恒定的死亡率，这可以量化病原体的致死率。然后，我们表明达到这一恒定死亡率状态所需的时间取决于病原体的生长率和定植率，从而决定了病原体的侵袭性。我们的框架表明，特别擅长宿主的初始定植，而则是定植不良，但一旦建立就同样致命。另一方面，定植能力强，一旦建立，致死率也很高。定量描述不同病原体完成这些步骤的能力的能力，对疾病的治疗和预防以及病原体的进化和生态学都有影响。
