The invasin D protein from Yersinia pseudotuberculosis selectively binds the Fab region of host antibodies and affects colonization of the intestine

Sadana, Pooja; Geyer, Rebecca; Pezoldt, Joern; Helmsing, Saskia; Huehn, Jochen; Hust, Michael; Dersch, Petra; Scrima, Andrea

doi:10.1074/jbc.ra117.001068

Cited by 601 publications

(25 citation statements)

References 95 publications

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“…A significant number of putative toxin genes associated with orfX-p47 clusters encoded proteins containing different types of motifs or domains correlated with the toxic properties. Among these, we have identified proteins harboring rearrangement hotspot (RHS) repeats present in a wide range of insecticidal toxins [35,36], ribosome inactivating protein domains [37], or bacterial immunoglobulin-like domains, the latter shown to be associated with intestinal colonization [38] and recently detected within the BoNT-like toxin encoded by Weissella oryzae [39]. Of note, these toxins share several common features, including oral infection route, proteolytic activation, and an ability to form pores in the target host cells [40][41][42][43].…”

Section: Association Of Orfx1 Orfx2 Orfx3 and P47 With Toxin Genesmentioning

confidence: 99%

Looking for the X Factor in Bacterial Pathogenesis: Association of orfX-p47 Gene Clusters with Toxin Genes in Clostridial and Non-Clostridial Bacterial Species

Nowakowska

Douillard

Lindström

2019

Toxins

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The botulinum neurotoxin (BoNT) has been extensively researched over the years in regard to its structure, mode of action, and applications. Nevertheless, the biological roles of four proteins encoded from a number of BoNT gene clusters, i.e., OrfX1-3 and P47, are unknown. Here, we investigated the diversity of orfX-p47 gene clusters using in silico analytical tools. We show that the orfX-p47 cluster was not only present in the genomes of BoNT-producing bacteria but also in a substantially wider range of bacterial species across the bacterial phylogenetic tree. Remarkably, the orfX-p47 cluster was consistently located in proximity to genes coding for various toxins, suggesting that OrfX1-3 and P47 may have a conserved function related to toxinogenesis and/or pathogenesis, regardless of the toxin produced by the bacterium. Our work also led to the identification of a putative novel BoNT-like toxin gene cluster in a Bacillus isolate. This gene cluster shares striking similarities to the BoNT cluster, encoding a bont/ntnh-like gene and orfX-p47, but also differs from it markedly, displaying additional genes putatively encoding the components of a polymorphic ABC toxin complex. These findings provide novel insights into the biological roles of OrfX1, OrfX2, OrfX3, and P47 in toxinogenesis and pathogenesis of BoNT-producing and non-producing bacteria.

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Section: Association Of Orfx1 Orfx2 Orfx3 and P47 With Toxin Genesmentioning

confidence: 99%

Looking for the X Factor in Bacterial Pathogenesis: Association of orfX-p47 Gene Clusters with Toxin Genes in Clostridial and Non-Clostridial Bacterial Species

Nowakowska

Douillard

Lindström

2019

Toxins

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“…InvD функционально и структурно относят к так называемым «иммуноглобулиновым суперантигенам», результатом связывания которых с Fabфрагментами антител или рецептором В-клеток могут быть пролиферация В-клеток, активация с последующей индукцией В-клеточного апоптоза, активация системы комплемента, стимуляция высвобождения цитокинов. Вторую группу иммуноглобулинсвязывающих бактериальных белков составляют белки, взаимодействующие с Fc-областью антител или Fcрецепторами макрофагов, что препятствует распознаванию патогена иммунной системой, повышает устойчивость к действию комплемента [58].…”

Section: белковые адгезины-аутотранспортерыunclassified

Yersinia pseudotuberculosis-derived adhesins

Byvalov

Konyshev

2019

Russian Journal of Infection and Immunity

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Around fifteen surface components referred to adhesins have been identified in Yersinia pseudotuberculosis combining primarily microbiological, molecular and genetic, as well as immunochemical and biophysical methods. Y. pseudotuberculosis-derived adhesins vary in structure and chemical composition but they are mainly presented by protein molecules. Some of them were shown to participate not only in adhesive but in other pathogen-related physiological functions in the host-parasite interplay. Adhesins can mediate bacterial adhesion to eukaryotic cell either directly or via the extracellular matrix components. These adhesion molecules are encoded by chromosomal DNA excepting YadA protein which gene is located in the calcium-dependence plasmid pYV common for pathogenic yersisniae. An optimum temperature for adhesin biosynthesis is located close to the body temperature of warm-blooded animals; however, at low temperature only invasin InvA, full-length smooth lipopolysaccharide and porin OmpF are produced in Y. pseudotuberculosis. Several adhesins (Psa, InvA) can be expressed at low pH (corresponds to intracellular content), thereby defining pathogenic yersiniae as facultative intracellular parasites. Three human Yersinia genus pathogens differ by ability to produce adhesins. Y. pseudotuberculosis adherence to host cells or extracellular matrix components is determined by a cumulative adhesion-based activity, which expression depends on chemical composition and physicochemical environmental conditions. It’s proposed that at the initial stage of infectious process adherence of Y. pseudotuberculosis to intestinal epithelium is mediated by InvA protein and “smooth” LPS form. These adhesins are produced in bacterial cells at low (lower than 30°С) temperature occurring in environment from which a pathogen invades into the host. At later stages of pathogenesis, after penetrating through intestinal epithelium, bacterial cells produce other adhesins, which promote survival and dissemination primarily into the mesenteric lymph nodes and, possibly, liver and spleen. At later stages of pathogenesis, after penetrating through intestinal epithelium, bacterial cells produce other adhesins, which promote survival and dissemination primarily into the mesenteric lymph nodes and, perhaps, liver and spleen. Qualitative and quantitative spectrum of Y. pseudotuberculosis adhesins is determined by environmental parameters (intercellular space, intracellular content within the diverse eukaryotic cells).

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“…In a new paper, Sadana et al (1) describe the identification and 3D structure of another bacterial protein that binds IgG to assist colonization of the host, but that binds to Fab rather than Fc. InvD is one of many virulence factors produced by the zoonotic pathogen Yersinia pseudotuberculosis.…”

mentioning

confidence: 99%

“…1 In further work the authors solved the crystal structure of the AD along with the two BIg domains preceding it. Unlike the ADs of other invasins, the InvD AD has an Ig-like fold but with extensive variations and insertions.…”

mentioning

confidence: 99%

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Grasping the nettle: A bacterial invasin that targets immunoglobulin variable domains

Barlow

2018

Journal of Biological Chemistry

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Edited by Ursula JakobIn a new paper, the protein InvD from Yersinia pseudotuberculosis, a zoonotic pathogen, is shown to assist late-stage invasion of intestinal epithelia. Remarkably, InvD acts by binding the Fab region of IgG or IgA. It straddles adjacent light-chain and heavy-chain variable domains, but its binding is different from that of antigens in that complementarity-determining regions do not participate. Structure determination revealed that its Fab-interacting domain adopts an immunoglobulin-like fold, fused to the preceding immunoglobulin-like domain and carried on a long stalk anchored to the bacterial outer membrane. Possible roles of this unusual host-pathogen interaction include avoidance of clearance from the intestine by secretory IgA.

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The invasin D protein from Yersinia pseudotuberculosis selectively binds the Fab region of host antibodies and affects colonization of the intestine

Cited by 601 publications

References 95 publications

Looking for the X Factor in Bacterial Pathogenesis: Association of orfX-p47 Gene Clusters with Toxin Genes in Clostridial and Non-Clostridial Bacterial Species

Looking for the X Factor in Bacterial Pathogenesis: Association of orfX-p47 Gene Clusters with Toxin Genes in Clostridial and Non-Clostridial Bacterial Species

Yersinia pseudotuberculosis-derived adhesins

Grasping the nettle: A bacterial invasin that targets immunoglobulin variable domains

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