In Vitro and In Vivo Model Systems for Studying Enteropathogenic Escherichia coli Infections

Law, Robyn J.; Gur-Arie, Lihi; Rosenshine, Ilan; Finlay, B. Brett

doi:10.1101/cshperspect.a009977

Cited by 62 publications

(59 citation statements)

References 129 publications

(134 reference statements)

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“…Pathogens have developed sophisticated ways to secrete proteins from the cytoplasmic compartment outside the bacterial cell. This allows the type III secretion systems (T3SS) of enteropathogenic E. coli (EPEC) and EHEC to insert a translocated intimin receptor into the host cell membrane, thus triggering the recruitment of actin directly underneath the attached bacteria to form pedestal structures leading to intimate attachment of the bacterium, resulting in characteristic A/E lesions on the brush border microvilli and in dramatic defects in the absorption/secretion functions (36,162,171,172). Some enterovirulent bacteria have developed sophisticated strategies for altering and opening the junctional domain of the intestinal epithelial barrier (6,173).…”

Section: Activities Against the Deleterious Effects Induced By Infectmentioning

confidence: 99%

Anti-Infective Activities of Lactobacillus Strains in the Human Intestinal Microbiota: from Probiotics to Gastrointestinal Anti-Infectious Biotherapeutic Agents

2014

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SUMMARY A vast and diverse array of microbial species displaying great phylogenic, genomic, and metabolic diversity have colonized the gastrointestinal tract. Resident microbes play a beneficial role by regulating the intestinal immune system, stimulating the maturation of host tissues, and playing a variety of roles in nutrition and in host resistance to gastric and enteric bacterial pathogens. The mechanisms by which the resident microbial species combat gastrointestinal pathogens are complex and include competitive metabolic interactions and the production of antimicrobial molecules. The human intestinal microbiota is a source from which Lactobacillus probiotic strains have often been isolated. Only six probiotic Lactobacillus strains isolated from human intestinal microbiota, i.e., L. rhamnosus GG, L. casei Shirota YIT9029, L. casei DN-114 001, L. johnsonii NCC 533, L. acidophilus LB, and L. reuteri DSM 17938, have been well characterized with regard to their potential antimicrobial effects against the major gastric and enteric bacterial pathogens and rotavirus. In this review, we describe the current knowledge concerning the experimental antibacterial activities, including antibiotic-like and cell-regulating activities, and therapeutic effects demonstrated in well-conducted, placebo-controlled, randomized clinical trials of these probiotic Lactobacillus strains. What is known about the antimicrobial activities supported by the molecules secreted by such probiotic Lactobacillus strains suggests that they constitute a promising new source for the development of innovative anti-infectious agents that act luminally and intracellularly in the gastrointestinal tract.

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Section: Activities Against the Deleterious Effects Induced By Infectmentioning

confidence: 99%

Anti-Infective Activities of Lactobacillus Strains in the Human Intestinal Microbiota: from Probiotics to Gastrointestinal Anti-Infectious Biotherapeutic Agents

2014

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“…EHEC is commonly associated with outbreaks of foodborne diarrheal illness in the developed world (4). The similarities between EPEC, EHEC, and C. rodentium infections have resulted in C. rodentium being widely used and recognized as a surrogate model to study intestinal infections caused by the human-restricted pathogens EPEC and EHEC (2,5,6).…”

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confidence: 99%

Systematic Analysis of Two-Component Systems in Citrobacter rodentium Reveals Positive and Negative Roles in Virulence

et al. 2017

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Citrobacter rodentium is a murine pathogen used to model intestinal infections caused by the human diarrheal pathogens enterohemorrhagic and enteropathogenic Escherichia coli. During infection, bacteria use two-component systems (TCSs) to detect changing environmental cues within the host, allowing for rapid adaptation by altering the expression of specific genes. In this study, 26 TCSs were identified in C. rodentium, and quantitative PCR (qPCR) analysis showed that they are all expressed during murine infection. These TCSs were individually deleted, and the in vitro and in vivo effects were analyzed to determine the functional consequences. In vitro analyses only revealed minor differences, and surprisingly, type III secretion (T3S) was only affected in the ΔarcA strain. Murine infections identified 7 mutants with either attenuated or increased virulence. In agreement with the in vitro T3S assay, the ΔarcA strain was attenuated and defective in colonization and cell adherence. The ΔrcsB strain was among the most highly attenuated strains. The decrease in virulence of this strain may be associated with changes to the cell surface, as Congo red binding was altered, and qPCR revealed that expression of the wcaA gene, which has been implicated in colanic acid production in other bacteria, was drastically downregulated. The ΔuvrY strain exhibited increased virulence compared to the wild type, which was associated with a significant increase in bacterial burden within the mesenteric lymph nodes. The systematic analysis of virulence-associated TCSs and investigation of their functions during infection may open new avenues for drug development.

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“…EHEC, a foodborne pathogen that causes watery or bloody diarrhea, is often associated with outbreaks (5). The mouse pathogen Citrobacter rodentium and rabbit EPEC (REPEC) have been used to model EPEC-and EHEC-induced human disease (6)(7)(8). C. rodentium is a nonmotile enteric pathogen that causes colonic hyperplasia, but typically not diarrhea, in mice.…”

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confidence: 99%

The Secreted Effector Protein EspZ Is Essential for Virulence of Rabbit Enteropathogenic Escherichia coli

et al. 2015

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e Attaching and effacing (A/E) pathogens adhere intimately to intestinal enterocytes and efface brush border microvilli. A key virulence strategy of A/E pathogens is the type III secretion system (T3SS)-mediated delivery of effector proteins into host cells. The secreted protein EspZ is postulated to promote enterocyte survival by regulating the T3SS and/or by modulating epithelial signaling pathways. To explore the role of EspZ in A/E pathogen virulence, we generated an isogenic espZ deletion strain (⌬espZ) and corresponding cis-complemented derivatives of rabbit enteropathogenic Escherichia coli and compared their abilities to regulate the T3SS and influence host cell survival in vitro. For virulence studies, rabbits infected with these strains were monitored for bacterial colonization, clinical signs, and intestinal tissue alterations. Consistent with data from previous reports, espZtransfected epithelial cells were refractory to infection-dependent effector translocation. Also, the ⌬espZ strain induced greater host cell death than did the parent and complemented strains. In rabbit infections, fecal ⌬espZ strain levels were 10-fold lower than those of the parent strain at 1 day postinfection, while the complemented strain was recovered at intermediate levels. In contrast to the parent and complemented mutants, ⌬espZ mutant fecal carriage progressively decreased on subsequent days. ⌬espZ mutant-infected animals gained weight steadily over the infection period, failed to show characteristic disease symptoms, and displayed minimal infection-induced histological alterations. Terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) staining of intestinal sections revealed increased epithelial cell apoptosis on day 1 after infection with the ⌬espZ strain compared to animals infected with the parent or complemented strains. Thus, EspZ-dependent host cell cytoprotection likely prevents epithelial cell death and sloughing and thereby promotes bacterial colonization.

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In Vitro and In Vivo Model Systems for Studying Enteropathogenic Escherichia coli Infections

Cited by 62 publications

References 129 publications

Anti-Infective Activities of Lactobacillus Strains in the Human Intestinal Microbiota: from Probiotics to Gastrointestinal Anti-Infectious Biotherapeutic Agents

Anti-Infective Activities of Lactobacillus Strains in the Human Intestinal Microbiota: from Probiotics to Gastrointestinal Anti-Infectious Biotherapeutic Agents

Systematic Analysis of Two-Component Systems in Citrobacter rodentium Reveals Positive and Negative Roles in Virulence

The Secreted Effector Protein EspZ Is Essential for Virulence of Rabbit Enteropathogenic Escherichia coli

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