Comparison ofIn VitroVirulence Factors ofCampylobacter jejunitoIn VivoLesion Production

Law, Bibiana; Adriance, Sarah M.; Joens, Lynn A.

doi:10.1089/fpd.2008.0183

Cited by 8 publications

(4 citation statements)

References 36 publications

(32 reference statements)

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“…The decreased ability of mouse-adapted C. jejuni to adhere and invade in cultured cells was unexpected since the ability to interact with gastrointestinal tract epithelial cells in vivo must be important for C. jejuni host colonization [46]. However, discordance between in vitro adherence and invasion results and in vivo virulence measures has been described before [47]. Also, screens using epithelial cell culture models have been unable to discover significant invasion factors, outside of genes affecting motility.…”

Section: Discussionmentioning

confidence: 99%

Standing Genetic Variation in Contingency Loci Drives the Rapid Adaptation of Campylobacter jejuni to a Novel Host

et al. 2011

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The genome of the food-borne pathogen Campylobacter jejuni contains multiple highly mutable sites, or contingency loci. It has been suggested that standing variation at these loci is a mechanism for rapid adaptation to a novel environment, but this phenomenon has not been shown experimentally. In previous work we showed that the virulence of C. jejuni NCTC11168 increased after serial passage through a C57BL/6 IL-10-/- mouse model of campylobacteriosis. Here we sought to determine the genetic basis of this adaptation during passage. Re-sequencing of the 1.64Mb genome to 200-500X coverage allowed us to define variation in 23 contingency loci to an unprecedented depth both before and after in vivo adaptation. Mutations in the mouse-adapted C. jejuni were largely restricted to the homopolymeric tracts of thirteen contingency loci. These changes cause significant alterations in open reading frames of genes in surface structure biosynthesis loci and in genes with only putative functions. Several loci with open reading frame changes also had altered transcript abundance. The increase in specific phases of contingency loci during in vivo passage of C. jejuni, coupled with the observed virulence increase and the lack of other types of genetic changes, is the first experimental evidence that these variable regions play a significant role in C. jejuni adaptation and virulence in a novel host.

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Section: Discussionmentioning

confidence: 99%

Standing Genetic Variation in Contingency Loci Drives the Rapid Adaptation of Campylobacter jejuni to a Novel Host

et al. 2011

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“…Few animal models have been developed for the study of Campylobacter pathology and virulence determinants [20][21][22][23]. Possible factors that aid in adhesion, invasion, and clinical disease include (1) resistance of the bacterial capsule to host-innate immunity, which may play a role in immune evasion; (2) flagellar proteins, which are utilized as a secretory apparatus necessary for invasion and adherence; (3) presence of a DNAse, cytolethal distending toxin (CDT) that causes apoptosis, although some data suggest that colitis can be produced by strains lacking CDT; and (4) capability of infective strains for N-and O-glycosylation, which may also contribute to immune evasion [24][25][26].…”

Section: Acute Campylobacteriosismentioning

confidence: 99%

The Chronic Gastrointestinal Consequences Associated With Campylobacter

Riddle

Gutiérrez

Verdú

et al. 2012

Curr Gastroenterol Rep

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Campylobacteriosis is a leading cause of acute infectious diarrhea in the developing world, where it causes considerable mortality, and in developed countries, where it accounts for significant healthcare and other costs. Evidence has emerged from basic science, clinical, and epidemiological domains that suggests that Campylobacter infection is not limited to acute illness but is also involved in the development of well-described extraintestinal sequelae, such as the Guillain-Barré syndrome and reactive arthritis, and may also contribute to the pathogenesis of chronic gastrointestinal conditions. This review will focus on the role of Campylobacter infection as a risk factor for the development of chronic gastrointestinal sequelae, such as functional gastrointestinal disorders, with which irritable bowel syndrome has been most frequently associated, inflammatory bowel disease, and celiac disease.

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“…The major contributing factor to our poor understanding of campylobacteriosis is the lack of robust experimental models mimicking the various phases of acute human infection. Although some mammals including monkey, 8 ferret 9 and piglet 10 have provided valuable information regarding cellular events associated with campylobacteriosis, limited reagents and lack of genetic manipulation in these models have constrained the generation of deep mechanistic understanding. We recently established an acute model of campylobacteriosis using germ-free Il10 −/− mice.…”

Section: Introductionmentioning

confidence: 99%

Campylobacter jejuni Induces Colitis Through Activation of Mammalian Target of Rapamycin Signaling

2012

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BACKGROUND & AIMS Campylobacter jejuni is the worldwide leading cause of bacterial-induced enteritis. The molecular and cellular events that lead to campylobacteriosis are poorly understood. We identify mammalian target of rapamycin (mTOR) as a signaling pathway that leads to C jejuni-induced intestinal inflammation. METHODS Germ-free (control) or conventionally-derived interleukin (Il)10−/− mice that express enhanced green fluorescent protein under the control of NF-κB (Il10 −/−; NF-κBEGFP mice) were infected with C jejuni (109 CFU/mouse) for 12 days; their responses were determined using histologic, semi-quantitative reverse transcription PCR, fluorescence in situ hybridization, transmission electron microscopy, and tissue culture analyses. mTOR signaling was blocked by daily intraperitoneal injections of the pharmacologic inhibitor rapamycin (1.5 mg/kg). CD4+ T cells were depleted by intraperitoneal injections of antibodies against CD4 (0.5 mg/mouse, every 3 days). Bacterial survival in splenocytes was measured using a gentamycin killing assay. RESULTS C jejuni induced intestinal inflammation, which correlated with activation of mTOR signaling and neutrophil infiltration. The inflamed intestines of these mice had increased levels of Il-1β, Cxcl2, Il-17a, and EGFP; C jejuni localized to colons and extra-intestinal tissues of infected Il10−/−; NF-κBEGFP mice, compared with controls. Rapamycin, administered before or after introduction of C jejuni, blocked C jejuni-induced intestinal inflammation and bacterial accumulation. LC3II processing and killing of C jejuni were increased in splenocytes incubated with rapamycin, compared with controls. CONCLUSIONS mTOR signaling mediates C jejuni-induced colitis in Il10−/− mice, independently of T-cell activation. Factors involved in mTOR signaling might be therapeutic targets for campylobacteriosis.

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Comparison ofIn VitroVirulence Factors ofCampylobacter jejunitoIn VivoLesion Production

Cited by 8 publications

References 36 publications

Standing Genetic Variation in Contingency Loci Drives the Rapid Adaptation of Campylobacter jejuni to a Novel Host

Standing Genetic Variation in Contingency Loci Drives the Rapid Adaptation of Campylobacter jejuni to a Novel Host

The Chronic Gastrointestinal Consequences Associated With Campylobacter

Campylobacter jejuni Induces Colitis Through Activation of Mammalian Target of Rapamycin Signaling

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