Histopathological Analysis of Salmonella Chronic Carriage in the Mouse Hepatopancreatobiliary System

Gonzalez-Escobedo, Geoffrey; Perle, Krista M. D. La

doi:10.1371/journal.pone.0084058

Cited by 24 publications

(23 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, S. Typhi gastrointestinal infection can facilitate gallbladder colonization and long-term carriage in 3 to 5% of infected individuals (47). Gallbladder carriage has been shown to be a result of biofilm formation on gallstones and the gallbladder epithelium and to increase the risk for gallbladder carcinoma (21,48,49). Bile enhances Salmonella biofilm formation on gallstone surfaces, implicating a bacterial response to bile that promotes persistence (50,51).…”

Section: Discussionmentioning

confidence: 99%

Bile Acids Function Synergistically To Repress Invasion Gene Expression in Salmonella by Destabilizing the Invasion Regulator HilD

et al. 2016

Self Cite

View full text Add to dashboard Cite

bSalmonella spp. are carried by and can acutely infect agricultural animals and humans. After ingestion, salmonellae traverse the upper digestive tract and initiate tissue invasion of the distal ileum, a virulence process carried out by the type III secretion system encoded within Salmonella pathogenicity island 1 (SPI-1). Salmonellae coordinate SPI-1 expression with anatomical location via environmental cues, one of which is bile, a complex digestive fluid that causes potent repression of SPI-1 genes. The individual components of bile responsible for SPI-1 repression have not been previously characterized, nor have the bacterial signaling processes that modulate their effects been determined. Here, we characterize the mechanism by which bile represses SPI-1 expression. Individual bile acids exhibit repressive activity on SPI-1-regulated genes that requires neither passive diffusion nor OmpF-mediated entry. By using genetic methods, the effects of bile and bile acids were shown to require the invasion gene transcriptional activator hilD and to function independently of known upstream signaling pathways. Protein analysis techniques showed that SPI-1 repression by bile acids is mediated by posttranslational destabilization of HilD. Finally, we found that bile acids function synergistically to achieve the overall repressive activity of bile. These studies demonstrate a common mechanism by which diverse environmental cues (e.g., certain short-chain fatty acids and bile acids) inhibit SPI-1 expression. These data provide information relevant to Salmonella pathogenesis during acute infection in the intestine and during chronic infection of the gallbladder and inform the basis for development of therapeutics to inhibit invasion as a means of repressing Salmonella pathogenicity.

show abstract

Section: Discussionmentioning

confidence: 99%

Bile Acids Function Synergistically To Repress Invasion Gene Expression in Salmonella by Destabilizing the Invasion Regulator HilD

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…Invasion of the gallbladder epithelium can mediate further damage to the organ and may permit bacterial escape from the harsh gallbladder environment [27]. Infected epithelial cells may proceed to re-initiate active gastrointestinal infection through a process of extrusion wherein bacterially infected epithelial cells are expelled from the epithelial layer by neighboring cells [29, 30]. Both models of persistent gallbladder infection (epithelial invasion/periodic extrusion and gallstone biofilm formation) likely involve a relatively small foci of bacteria associated with ongoing, low-level gallbladder damage and inflammation with intermittent re-seeding of the GI tract with viable bacteria.…”

Section: The Mechanisms Of Salmonella Persistence In the Gallbladdermentioning

confidence: 99%

“…The clinical association between S . Typhi infection and malignancy is supported by studies employing a murine model of long-term gallbladder carriage of Salmonella in which histopathological analysis of gallbladder tissue revealed significant pathology from the presence of gallstones alone, but pre-malignant transformations were present only in the gallbladders of mice with chronic Salmonella infections [30]. …”

Section: The Mechanisms Of Salmonella Persistence In the Gallbladdermentioning

confidence: 99%

Salmonella chronic carriage: epidemiology, diagnosis, and gallbladder persistence

Gunn

Marshall

Baker

et al. 2014

Trends in Microbiology

Self Cite

245

242

View full text Add to dashboard Cite

Typhoid (enteric fever) remains a major cause of morbidity and mortality worldwide, causing over 21 million new infections annually, with the majority of deaths occurring in young children. As typhoid fever-causing Salmonella have no known environmental reservoir, the chronic, asymptomatic carrier state is thought to be a key feature of continued maintenance of the bacterium within human populations. In spite of the importance of this disease to public health, our understanding of the molecular mechanisms that catalyze carriage, as well as our ability to reliably identify and treat the Salmonella carrier state, have only recently begun to advance.

show abstract

“…Salmonella's ability to persist within the gallbladder of a significant fraction of patients (2-5%) after systemic infection appears to provide the milieu for its tumor-promoting effect. Initial experimental evidence in mice supports an association between Salmonella infection and GBC, as long-term histopathological follow-up of chronically infected mice revealed pre-malignant lesions with hyperplasia and metaplasia of the gallbladder [5]. Now, Scanu and colleagues provide insights into the molecular mechanisms underlying this association [1].…”

Section: See Also: T Scanu Et Al (June 2015)mentioning

confidence: 97%

The deadly bite of Salmonella Typhi

Zhang

Hornef

Fulde³

2015

EMBO Reports

View full text Add to dashboard Cite

Pathogenic microorganisms overcome the host's innate and adaptive immune system and cause local or systemic infections, potentially leading to organ failure, sepsis, or even death. Some microorganisms can also directly or indirectly alter the differentiation and proliferation of host cells, promoting the development of tumors. A large number of oncogenic viruses have been identified and estimated to account for ~15% of human cancers. They do so by encoding oncogenes or through their intrinsic ability to manipulate the genomic stability of the host cell by integrating their own genetic elements. Also bacterial infections have been linked to carcinogenesis, although the underlying molecular mechanisms are less well understood. The best‐studied example is Helicobacter pylori, which has been classified as a class I carcinogen by the World Health Organization due to its ability to promote stomach cancer after chronic infection, which causes tissue inflammation and atrophy of the gastric mucosa. In a recent issue of Cell Host & Microbe, the Neefjes laboratory explores the association between Salmonella enterica subsp. enterica sv. Typhi (S. Typhi)—which is the causative agent of human typhoid fever—and gallbladder carcinoma .

show abstract

Histopathological Analysis of Salmonella Chronic Carriage in the Mouse Hepatopancreatobiliary System

Cited by 24 publications

References 74 publications

Bile Acids Function Synergistically To Repress Invasion Gene Expression in Salmonella by Destabilizing the Invasion Regulator HilD

Bile Acids Function Synergistically To Repress Invasion Gene Expression in Salmonella by Destabilizing the Invasion Regulator HilD

Salmonella chronic carriage: epidemiology, diagnosis, and gallbladder persistence

The deadly bite of Salmonella Typhi

Contact Info

Product

Resources

About