Disentangling bacterial invasiveness from lethality in an experimental host‐pathogen system
Name
msb.20188707.pdf
Description
Published version
Size
890.67 KB
Format
Adobe PDF
Checksum (MD5)
f0035a27dc393d89e2d0d5781d239e8c
Author(s)
Biancalani, Tommaso
Gore, Jeff
Date Issued
June 2019
Journal
Molecular Systems Biology
Publisher
EMBO
Citation
Biancalani, Tommaso and Jeff Gore. "Disentangling bacterial invasiveness from lethality in an experimental host‐pathogen system." Molecular Systems Biology 15, 6 (June 2019): e8707 © 2019 The Authors.
Version
Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Physics
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.15252/msb.20188707
