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Bacterial Population Dynamics and Ho...

Peterson, Stefan Thomas,

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Bacterial Population Dynamics and Host Factors Influencing Yersinia Extraintestinal Dissemination /

Record Type:	Electronic resources : Monograph/item
Title/Author:	Bacterial Population Dynamics and Host Factors Influencing Yersinia Extraintestinal Dissemination // Stefan Thomas Peterson.
Author:	Peterson, Stefan Thomas,
Description:	1 electronic resource (118 pages)
Notes:	Source: Dissertations Abstracts International, Volume: 86-12, Section: B.
Contained By:	Dissertations Abstracts International86-12B.
Subject:	Microbiology. -
Online resource:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=31995389
ISBN:	9798280759329

Bacterial Population Dynamics and Host Factors Influencing Yersinia Extraintestinal Dissemination /
Peterson, Stefan Thomas,

Bacterial Population Dynamics and Host Factors Influencing Yersinia Extraintestinal Dissemination /Stefan Thomas Peterson. - 1 electronic resource (118 pages)

Source: Dissertations Abstracts International, Volume: 86-12, Section: B.

The mammalian host employs multiple layers of physical and chemical defenses to restrict invading pathogens, creating bottlenecks that limit microbial colonization. However, pathogenic microbes possess virulence factors that allow them to evade these defenses and establish infection. Enteric bacterial pathogens pose a significant global disease burden, with some capable of invading intestinal tissue and disseminating to other organs, leading to severe outcomes such as organ damage, sepsis, and death. Despite this, the population dynamics underlying invasive bacterial infections remain poorly understood.Yersinia pseudotuberculosis (Y. ptb), a Gram-negative pathogen related to Y. pestis, infects the human gastrointestinal tract and can cause severe disease in immunocompromised hosts. As a naturally rodent-adapted pathogen, Y. ptb infection in mice serves as a model for severe human disease. Using a novel barcoded Y. ptb library and the Sequence Tag-based Analysis of Microbial Populations in R (STAMPR) system, we identify a severe restriction in Y. ptb clones from inoculation to intestinal colonization and tissue invasion following oral infection. We find that intestinal colonization bottlenecks are influenced by inoculation method and the endogenous microbiota, whereas tissue invasion remains tightly restricted regardless of these factors. Additionally, we demonstrate that the luminal Y. ptb population is dynamic, with Y. ptb clones shed in stool fluctuating over the course of infection.We find that the tight bottleneck for Y. ptb invasion is partially mediated by TNF signaling, as TNFR1-deficient mice harbor more unique Y. ptb clones at each infection site. Notably, TNF signaling contributes to the containment of Y. ptb within intestinal pyogranulomas, which in immunocompetent mice remain clonal and do not disseminate. Furthermore, we demonstrate that Y. ptb spreads extra intestinally in waves, translocating directly from the gastrointestinal tract into the bloodstream without prior replication, leading to a shared bacterial population in the blood, liver, and spleen within days of infection. While lymphatic spread has been proposed, our findings indicate that the mesenteric lymph nodes act as a restrictive site in wild-type mice, a function that is lost in the absence of TNF signaling. Overall, this work elucidates the complex interplay of host factors shaping Y. ptb population dynamics during infection, quantifying the bottlenecks to intestinal colonization and tissue invasion. These findings enhance our understanding of Y. ptb invasive infection and may inform the development of therapeutics for severe invasive bacterial infections.

English

ISBN: 9798280759329Subjects--Topical Terms:

536250
Microbiology.
Subjects--Index Terms:

Bacterial pathogens

Bacterial Population Dynamics and Host Factors Influencing Yersinia Extraintestinal Dissemination /
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500 $a Source: Dissertations Abstracts International, Volume: 86-12, Section: B.
500 $a Advisors: Brodsky, Igor E. Committee members: Grice, Elizabeth A.; Zackular, Joseph P.; Silverman, Michael; Planet, Paul J.
502 $b Ph.D. $c University of Pennsylvania $d 2025.
520 $a The mammalian host employs multiple layers of physical and chemical defenses to restrict invading pathogens, creating bottlenecks that limit microbial colonization. However, pathogenic microbes possess virulence factors that allow them to evade these defenses and establish infection. Enteric bacterial pathogens pose a significant global disease burden, with some capable of invading intestinal tissue and disseminating to other organs, leading to severe outcomes such as organ damage, sepsis, and death. Despite this, the population dynamics underlying invasive bacterial infections remain poorly understood.Yersinia pseudotuberculosis (Y. ptb), a Gram-negative pathogen related to Y. pestis, infects the human gastrointestinal tract and can cause severe disease in immunocompromised hosts. As a naturally rodent-adapted pathogen, Y. ptb infection in mice serves as a model for severe human disease. Using a novel barcoded Y. ptb library and the Sequence Tag-based Analysis of Microbial Populations in R (STAMPR) system, we identify a severe restriction in Y. ptb clones from inoculation to intestinal colonization and tissue invasion following oral infection. We find that intestinal colonization bottlenecks are influenced by inoculation method and the endogenous microbiota, whereas tissue invasion remains tightly restricted regardless of these factors. Additionally, we demonstrate that the luminal Y. ptb population is dynamic, with Y. ptb clones shed in stool fluctuating over the course of infection.We find that the tight bottleneck for Y. ptb invasion is partially mediated by TNF signaling, as TNFR1-deficient mice harbor more unique Y. ptb clones at each infection site. Notably, TNF signaling contributes to the containment of Y. ptb within intestinal pyogranulomas, which in immunocompetent mice remain clonal and do not disseminate. Furthermore, we demonstrate that Y. ptb spreads extra intestinally in waves, translocating directly from the gastrointestinal tract into the bloodstream without prior replication, leading to a shared bacterial population in the blood, liver, and spleen within days of infection. While lymphatic spread has been proposed, our findings indicate that the mesenteric lymph nodes act as a restrictive site in wild-type mice, a function that is lost in the absence of TNF signaling. Overall, this work elucidates the complex interplay of host factors shaping Y. ptb population dynamics during infection, quantifying the bottlenecks to intestinal colonization and tissue invasion. These findings enhance our understanding of Y. ptb invasive infection and may inform the development of therapeutics for severe invasive bacterial infections.
546 $a English
590 $a School code: 0175
650 4 $a Microbiology. $3 536250
650 4 $a Cellular biology. $3 3172791
650 4 $a Pathology. $3 643180
650 4 $a Molecular biology. $3 517296
653 $a Bacterial pathogens
653 $a Yersinia pseudotuberculosis
653 $a Population dynamics
653 $a Organ damage
690 $a 0410
690 $a 0379
690 $a 0307
690 $a 0571
710 2 $a University of Pennsylvania. $b Cell and Molecular Biology. $e degree granting institution. $3 3824999
720 1 $a Brodsky, Igor E. $e degree supervisor.
773 0 $t Dissertations Abstracts International $g 86-12B.
790 $a 0175
791 $a Ph.D.
792 $a 2025
856 4 0 $u https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=31995389