Skip to Main Content
 

Global Search Box

 
 
 

ETD Abstract Container

Abstract Header

Salmonella spp. Interactions with the Gallbladder during Chronic Carriage

Gonzalez-Escobedo, Geoffrey
http://rave.ohiolink.edu/etdc/view?acc_num=osu1374146434

Abstract Details

2013, Doctor of Philosophy, Ohio State University, Microbiology.
Salmonella enterica serovar Typhi (S. Typhi) is an important human pathogen and the etiologic agent of typhoid fever. Despite advances in modern medicine, typhoid fever is still a significant cause of mortality worldwide. Although most studies focus on the initial stages of the disease, this successful enteric pathogen is able to persist chronically in the gallbladder of some patients. Shedding of S. Typhi by these asymptomatic carriers can contaminate food and water supplies, especially in underdeveloped countries, and as such be a source of recurring Salmonella infections. This chronic carrier state is often associated with the presence of gallstones in the gallbladder. Biofilm formation on the surface of cholesterol gallstones has been demonstrated to be a mechanism of chronic colonization and carriage in the gallbladder of mice and human carriers. In this study, we identified genes specifically up-regulated during biofilm development on cholesterol surfaces by using an in vitro model that mimics the gallbladder and gallstones environment. These genes encode the surface proteins type 1 fimbriae and YcfR. To validate the role of these genes in vivo, we used our mouse model of Salmonella chronic carriage. This study strongly suggests that type 1 fimbriae are important for persistent attachment on cholesterol gallstones whereas ycfR seems to negatively modulate biofilm formation on cholesterol gallstones. This is the first study to profile gene expression of Salmonella during biofilm development on gallstones with further evaluation in a mouse model of chronic carriage. As part of our effort to fully understand the mechanisms of Salmonella persistence, we also examined the gallbladder epithelium as a potential additional niche for chronic carriage. Here we present evidence demonstrating the ability of Salmonella to also persist in gallbladder tissue both intracellularly and extracellularly (as micro-colonies or biofilms) in/on the epithelium and that heavily infected host cells can be extruded from the epithelium. In addition, we also analyzed the histopathological features of chronic carriage up to 1 year post-infection demonstrating that chronic cholecystitis and hepatitis were present in infected mice regardless of the presence of gallstones. At most time points, the mere presence of gallstones caused more gallbladder inflammation than chronic salmonellosis. However, only Salmonella chronic inflammation induced pre-malignant lesions (atypical hyperplasia and metaplasia) of the gallbladder and pancreas epithelium. This study has implications regarding the role of Salmonella chronic infection and inflammation in oncogenesis. Finally, the genome sequencing of a hyper-biofilm forming strain isolated from the gallstone of a carrier mouse nine months post-infection revealed 14 single nucleotide polymorphisms that may represent a specific adaptation of Salmonella to the gallbladder and gallstones environment during long-term carriage. Taken together, these results reveal the complicated nature of the mechanisms governing chronic carriage in the gallbladder (with or without gallstones) including biofilm formation on gallstones and gallbladder epithelium, intracellular persistence in the gallbladder epithelium, chronic inflammation with development of pre-malignant lesions and mutational adaptation during long-term carriage. Gaining a better understanding of the specific mechanisms of chronic carriage in the gallbladder may contribute to the development of effective strategies to prevent/treat this chronic, biofilm-mediated infection.
John Gunn, S. (Advisor)
Daniel Wozniak (Committee Member)
258 p.
Microbiology
Salmonella; gallbladder; chronic carriage; typhoid fever

Recommended Citations

Citations

  • Gonzalez-Escobedo, G. (2013). Salmonella spp. Interactions with the Gallbladder during Chronic Carriage [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1374146434

    APA Style (7th edition)

  • Gonzalez-Escobedo, Geoffrey. Salmonella spp. Interactions with the Gallbladder during Chronic Carriage. 2013. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1374146434.

    MLA Style (8th edition)

  • Gonzalez-Escobedo, Geoffrey. "Salmonella spp. Interactions with the Gallbladder during Chronic Carriage." Doctoral dissertation, Ohio State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=osu1374146434

    Chicago Manual of Style (17th edition)

osu1374146434
3,735
© 2013, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.