Details

Autor(en) / Beteiligte

• Biancalani, Tommaso
• Gore, Jeff

Titel

Disentangling bacterial invasiveness from lethality in an experimental host‐pathogen system

Ist Teil von

• Molecular systems biology, 2019-06, Vol.15 (6), p.e8707-n/a

Ort / Verlag

England: EMBO Press

Erscheinungsjahr

2019

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Quantifying virulence remains a central problem in human health, pest control, disease ecology, and evolutionary biology. Bacterial virulence is typically quantified by the LT50 (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 Caenorhabditis elegans nematodes exposed to three bacterial pathogens: Pseudomonas aeruginosa, Serratia marcescens, and Salmonella enterica. 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 Serratia marcescens is particularly good at the initial colonization of the host, whereas Salmonella enterica is a poor colonizer yet just as lethal once established. Pseudomonas aeruginosa, 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. Synopsis Mathematical modeling and quantitative analyses of survival curves of C. elegans exposed to three pathogens allow distinguishing between pathogen invasiveness and lethality and reveal quantitative laws of host‐pathogen dynamics. Survival dynamics is analysed in a C. elegans population exposed to three bacterial pathogens: Pseudomonas aeruginosa, Serratia marcescens and Salmonella enterica. The host population eventually experiences a constant mortality rate, which quantifies the lethality of the pathogen. The time required to reach this constant‐mortality rate regime depends on the pathogen growth rate and colonization rate, and thus determines the pathogen invasiveness. These indicators are used to characterize how these pathogens kill the host population. Mathematical modeling and quantitative analyses of survival curves of C. elegans exposed to three pathogens allow distinguishing between pathogen invasiveness and lethality and reveal quantitative laws of host‐pathogen dynamics.