Humoral Immunity in the Gut Selectively Targets Phenotypically Virulent Attaching-and-Effacing Bacteria for Intraluminal Elimination

Kamada, Nobuhiko; Sakamoto, Kei; Seo, Sang Uk; Zeng, Melody Y.; Kim, Yun Gi; Cascalho, Marília; Vallance, Bruce A.; Puente, José L.; Núñez, Gabriel

doi:10.1016/j.chom.2015.04.001

Cited by 132 publications

(177 citation statements)

References 34 publications

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“…C. rodentium resembles V. cholerae (37) in its ability to elicit a strong immune response during infection, which leads to clearance of the infection (reviewed for C. rodentium in ref. 38). Earlier work on C. rodentium (39) showed that, in otherwise germ-free mice, the organisms can colonize for up to 6 wk (the longest period tested).…”

Section: Resultsmentioning

confidence: 99%

“…Earlier work on C. rodentium (39) showed that, in otherwise germ-free mice, the organisms can colonize for up to 6 wk (the longest period tested). However, colonization of the epithelial cell surface was limited to ∼2 wk, which is attributed to the development of the immune response (38). Long-term survival of the bacteria was found only in the lumen and only occurred in otherwise germ-free mice, showing that C. rodentium cannot compete with normally commensal organisms (38).…”

Section: Resultsmentioning

confidence: 99%

“…However, colonization of the epithelial cell surface was limited to ∼2 wk, which is attributed to the development of the immune response (38). Long-term survival of the bacteria was found only in the lumen and only occurred in otherwise germ-free mice, showing that C. rodentium cannot compete with normally commensal organisms (38). The 5-wklong persistence of the Middle East V. cholerae strain in the intestine (see above) suggests that this strain also occupies the intestinal lumen, rather than attaching to epithelial cell surfaces, as is typically the case during infection with V. cholerae.…”

Section: Resultsmentioning

confidence: 99%

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Origins of the current seventh cholera pandemic

Liu

Feng

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

171

139

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Vibrio choleraehas caused seven cholera pandemics since 1817, imposing terror on much of the world, but bacterial strains are currently only available for the sixth and seventh pandemics. The El Tor biotype seventh pandemic began in 1961 in Indonesia, but did not originate directly from the classical biotype sixth-pandemic strain. Previous studies focused mainly on the spread of the seventh pandemic after 1970. Here, we analyze in unprecedented detail the origin, evolution, and transition to pandemicity of the seventh-pandemic strain. We used high-resolution comparative genomic analysis of strains collected from 1930 to 1964, covering the evolution from the first available El Tor biotype strain to the start of the seventh pandemic. We define six stages leading to the pandemic strain and reveal all key events. The seventh pandemic originated from a nonpathogenic strain in the Middle East, first observed in 1897. It subsequently underwent explosive diversification, including the spawning of the pandemic lineage. This rapid diversification suggests that, when first observed, the strain had only recently arrived in the Middle East, possibly from the Asian homeland of cholera. The lineage migrated to Makassar, Indonesia, where it gained the important virulence-associated elementsVibrioseventh pandemic island I (VSP-I), VSP-II, and El Tor type cholera toxin prophage by 1954, and it then became pandemic in 1961 after only 12 additional mutations. Our data indicate that specific niches in the Middle East and Makassar were important in generating the pandemic strain by providing gene sources and the driving forces for genetic events.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Origins of the current seventh cholera pandemic

Liu

Feng

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

171

139

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“…Bifidobacteria supplementation in patients -evidence from clinical trials Disturbances in the microbiota are linked to an ever-growing number of immune-linked disease states including IBD, atopic allergy, arthritis, and obesity [80]. Therefore, there is a significant interest in treating these diseases through microbial or 'probiotic' supplementation of patients, including with Bifidobacterium.…”

Section: Other Cells Typesmentioning

confidence: 99%

Exploring the role of the microbiota member Bifidobacterium in modulating immune-linked diseases

O’Neill

Schofield

Hall

2017

Emerging Topics in Life Sciences

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The gut-associated microbiota is essential for multiple physiological processes, including immune development. Acquisition of our initial pioneer microbial communities, including the dominant early life genus Bifidobacterium, occurs at a critical period of immune maturation and programming. Bifidobacteria are resident microbiota members throughout our lifetime and have been shown to modulate specific immune cells and pathways. Notably, reductions in this genus have been associated with several diseases, including inflammatory bowel disease. In this review, we provide an overview of bifidobacteria profiles throughout life and how different strains of bifidobacteria have been implicated in immune modulation in disease states. The focus will be examining preclinical models and outcomes from clinical trials on immune-linked chronic conditions. Finally, we highlight some of the important unresolved questions in relation to Bifidobacterium-mediated immune modulation and implications for future directions, trials, and development of new therapies.

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“…Antiadhesin IgG antibody isotypes mediate neutrophil-dependent clearance of the enteropathogen Citrobacter rodentium from rodents (24), and in cases of ETEC and uropathogenic Escherichia coli (UPEC), antifimbrial IgGs severely limit the biomechanical resilience of CS20 and P fimbriae, respectively (25,26). This resilience is important for reducing the force on the adhesin when bacteria are exposed to shearing fluid forces in both intestinal and extraintestinal milieus (27,28).…”

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confidence: 99%

Antibodies Damage the Resilience of Fimbriae, Causing Them To Be Stiff and Tangled

et al. 2017

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As adhesion fimbriae are a major virulence factor for many pathogenic Gram-negative bacteria, they are also potential targets for antibodies. Fimbriae are commonly required for initiating the colonization that leads to disease, and their success as adhesion organelles lies in their ability to both initiate and sustain bacterial attachment to epithelial cells. The ability of fimbriae to unwind and rewind their helical filaments presumably reduces their detachment from tissue surfaces with the shear forces that accompany significant fluid flow. Therefore, the disruption of functional fimbriae by inhibiting this resilience should have high potential for use as a vaccine to prevent disease. In this study, we show that two characteristic biomechanical features of fimbrial resilience, namely, the extension force and the extension length, are significantly altered by the binding of antibodies to fimbriae. The fimbriae that were studied are normally expressed on enterotoxigenic Escherichia coli, which are a major cause of diarrheal disease. This alteration in biomechanical properties was observed with bivalent polyclonal antifimbrial antibodies that recognize major pilin subunits but not with the Fab fragments of these antibodies. Thus, we propose that the mechanism by which bound antibodies disrupt the uncoiling of natural fimbria under force is by clamping together layers of the helical filament, thereby increasing their stiffness and reducing their resilience during fluid flow. In addition, we propose that antibodies tangle fimbriae via bivalent binding, i.e., by binding to two individual fimbriae and linking them together. Use of antibodies to disrupt physical properties of fimbriae may be generally applicable to the large number of Gram-negative bacteria that rely on these surface-adhesion molecules as an essential virulence factor. IMPORTANCE Our study shows that the resiliency of colonization factor antigen I (CFA/I) and coli surface antigen 2 (CS2) fimbriae, which are current targets for vaccine development, can be compromised significantly in the presence of antifimbrial antibodies. It is unclear how the humoral immune system specifically interrupts infection after the attachment of enterotoxigenic Escherichia coli (ETEC) to the epithelial surface. Our study indicates that immunoglobulins, in addition to their welldocumented role in adaptive immunity, can mechanically damage the resilience of fimbriae of surface-attached ETEC, thereby revealing a new mode of action. Our data suggest a mechanism whereby antibodies coat adherent and free-floating bacteria to impede fimbrial resilience. Further elucidation of this possible mechanism is likely to inform the development and refinement of preventive vaccines against ETEC diarrhea.KEYWORDS pili, IgG, vaccine, CFA/I, CS2, optical tweezers

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Humoral Immunity in the Gut Selectively Targets Phenotypically Virulent Attaching-and-Effacing Bacteria for Intraluminal Elimination

Cited by 132 publications

References 34 publications

Origins of the current seventh cholera pandemic

Origins of the current seventh cholera pandemic

Exploring the role of the microbiota member Bifidobacterium in modulating immune-linked diseases

Antibodies Damage the Resilience of Fimbriae, Causing Them To Be Stiff and Tangled

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