Cristin-resultat-ID: 1971841
Sist endret: 15. mars 2022, 09:28
NVI-rapporteringsår: 2021
Resultat
Vitenskapelig artikkel
2021

The Infectious Dose Shapes Vibrio Cholerae Within-Host Dynamics

Bidragsytere:
  • Aaron Nicholas Gillman
  • Anel Mahmutovic
  • Pia Abel zur Wiesch og
  • Sören Abel

Tidsskrift

mSystems
ISSN 2379-5077
e-ISSN 2379-5077
NVI-nivå 1

Om resultatet

Vitenskapelig artikkel
Publiseringsår: 2021
Publisert online: 2021
Volum: 6
Hefte: 6
Sider: 1 - 19
Open Access

Importkilder

Scopus-ID: 2-s2.0-85122625517

Beskrivelse Beskrivelse

Tittel

The Infectious Dose Shapes Vibrio Cholerae Within-Host Dynamics

Sammendrag

During infection, the rates of pathogen replication, death, and migration affect disease progression, dissemination, transmission, and resistance evolution. Here, we follow the population dynamics of Vibrio cholerae in a mouse model by labeling individual bacteria with one of >500 unique, fitness-neutral genomic tags. Using the changes in tag frequencies and CFU numbers, we inform a mathematical model that describes the within-host spatiotemporal bacterial dynamics. This allows us to disentangle growth, death, forward, and retrograde migration rates continuously during infection. Our model has robust predictive power across various experimental setups. The population dynamics of V. cholerae shows substantial spatiotemporal heterogeneity in replication, death, and migration. Importantly, we find that the niche available to V. cholerae in the host increases with inoculum size, suggesting cooperative effects during infection. Therefore, it is not enough to consider just the likelihood of exposure (50% infectious dose) but rather the magnitude of exposure to predict outbreaks. IMPORTANCE Determining the rates of bacterial migration, replication, and death during infection is important for understanding how infections progress. Separately measuring these rates is often difficult in systems where multiple processes happen simultaneously. Here, we use next-generation sequencing to measure V. cholerae migration, replication, death, and niche size along the mouse gastrointestinal tract. We show that the small intestine of the mouse is a heterogeneous environment, and the population dynamic characteristics change substantially between adjacent gut sections. Our approach also allows us to characterize the effect of inoculum size on these processes. We find that the niche size in mice increases with the infectious dose, hinting at cooperative effects in larger inocula. The dose-response relationship between inoculum size and final pathogen burden is important for the infected individual and is thought to influence the progression of V. cholerae epidemics. INTRODUCTION During bacterial infections

Bidragsytere

Aaron Nicholas Gillman

  • Tilknyttet:
    Forfatter
    ved Pennsylvania State University
  • Tilknyttet:
    Forfatter
    ved Computational Pharmacology, Research Group ved UiT Norges arktiske universitet

Anel Mahmutovic

  • Tilknyttet:
    Forfatter
    ved Infection Biologi, Research Group ved UiT Norges arktiske universitet

Pia Karoline Abel-Zur Wiesch Genannt Hülsho

Bidragsyterens navn vises på dette resultatet som Pia Abel zur Wiesch
  • Tilknyttet:
    Forfatter
    ved Pennsylvania State University
  • Tilknyttet:
    Forfatter
    ved Norsk Senter for Molekylærmedisin ved Universitetet i Oslo
  • Tilknyttet:
    Forfatter
    ved Computational Pharmacology, Research Group ved UiT Norges arktiske universitet
  • Tilknyttet:
    Forfatter
    ved USA

Sören Abel

  • Tilknyttet:
    Forfatter
    ved Norsk Senter for Molekylærmedisin (NCMM) Admin og kjernefasiliteter ved Universitetet i Oslo
  • Tilknyttet:
    Forfatter
    ved Infection Biologi, Research Group ved UiT Norges arktiske universitet
  • Tilknyttet:
    Forfatter
    ved Pennsylvania State University
  • Tilknyttet:
    Forfatter
    ved USA
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