Binding of Clostridium perfringens to collagen correlates with the ability to cause necrotic enteritis in chickens

Wade, Ben; Keyburn, Anthony L.; Seemann, Torsten; Rood, Julian I.; Moore, Robert J.

doi:10.1016/j.vetmic.2015.09.019

Cited by 79 publications

(73 citation statements)

References 24 publications

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“…Like netB , cnaA was significantly present among NE isolates from chickens compared to a single NE isolate from a turkey (Table 1). Wade et al [11] found cnaA only in diseased chickens whereas another study [22] also identified cnaA in isolates from healthy chickens. Additionally, NELoc-2 and -3 were also primarily found in isolates from diseased chickens.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, a putative collagen adhesion gene was discovered in all diseased turkeys and according to a suggested lettering system presented by Wade et al [11], it has here been designated as cnaD . This gene encodes a vWF type A domain and three Cna protein B-type domains.…”

Section: Discussionmentioning

confidence: 99%

“…Two other loci have also been found to be associated with NE in chickens, NELoc-2 (11.2 kb) and NELoc-3 (5.6 kb), which are chromosomally and plasmid-encoded respectively [10]. Furthermore, a recent study showed that a collagen adhesion gene, cnaA is involved in NE in chickens [11]. …”

Section: Introductionmentioning

confidence: 99%

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Genome analysis of Clostridium perfringens isolates from healthy and necrotic enteritis infected chickens and turkeys

Ronco

Stegger

et al. 2017

BMC Res Notes

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Objective Clostridium perfringens causes gastrointestinal diseases in both humans and domestic animals. Type A strains expressing the NetB toxin are the main cause of necrotic enteritis (NE) in chickens, which has remarkable impact on animal welfare and production economy in the international poultry industry. Three pathogenicity loci NELoc-1, -2 and -3 and a collagen adhesion gene cnaA have been found to be associated with NE in chickens, whereas the presence of these has not been investigated in diseased turkeys. The purpose was to investigate the virulence associated genome content and the genetic relationship among 30 C. perfringens isolates from both healthy and NE infected chickens and turkeys, applying whole-genome sequencing.ResultsNELoc-1, -3, netB and cnaA were significantly associated with NE isolates from chickens, whereas only NELoc-2 was commonly observed in both diseased turkeys and chickens. A putative collagen adhesion gene that encodes a von Willebrand Factor (vWF) domain was identified in all diseased turkeys and designated as cnaD. The phylogenetic analysis based on single nucleotide polymorphisms showed that the isolates generally were not closely related. These results indicate that virulence factors and pathogenicity loci associated with NE in chickens are not important to the same extent in diseased turkeys except for NELoc-2. A putative collagen adhesion gene which potentially could be of importance in regard to the NE pathogenesis in turkeys was identified and need to be further investigated. Thus, the pathogenesis of NE in turkeys appears to be different from that of broiler chickens.Electronic supplementary materialThe online version of this article (doi:10.1186/s13104-017-2594-9) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Genome analysis of Clostridium perfringens isolates from healthy and necrotic enteritis infected chickens and turkeys

Ronco

Stegger

et al. 2017

BMC Res Notes

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“…Interestingly, two genes (CP4_0573 and CP4_0575) identified in a previous comparative genomic screen for NE-associated loci (38) were found to be positively regulated by Agr-like QS, further implicating a role for this locus in NE pathogenesis. These two genes are part of a larger cluster of seven genes, designated VR-10B, that encode a collagen adhesin, sortases, and structural proteins predicted to produce an adhesive pilus (30,38). Two operons involved in the phosphotidylethanolamine (PE) catabolic pathway were also differentially expressed in CP1⍀agrB; specifically, the dha and eut operons, responsible for the breakdown of the PE metabolites glycerol and ethanolamine, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…7B). Additionally, three closely linked genes (CP4_1816, CP4_1817, and CP4_1819) involved in the phosphotransferase (PTS) sugar uptake system were upregulated in CP1⍀agrB and two genes (CP4_0573 and CP4_0575) that are part of a larger operon recently identified as involved in adhesion (30) were downregulated in CP1⍀agrB.…”

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confidence: 99%

The Agr-Like Quorum Sensing System Is Required for Pathogenesis of Necrotic Enteritis Caused by Clostridium perfringens in Poultry

Lepp

Gohari

et al. 2017

Infect Immun

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Clostridium perfringens encodes at least two different quorum sensing (QS) systems, the Agr-like and LuxS, and recent studies have highlighted their importance in the regulation of toxin production and virulence. The role of QS in the pathogenesis of necrotic enteritis (NE) in poultry and the regulation of NetB, the key toxin involved, has not yet been investigated. We have generated isogenic agrB-null and complemented strains from parent strain CP1 and demonstrated that the virulence of the agrB-null mutant was strongly attenuated in a chicken NE model system and restored by complementation. The production of NetB, a key NE-associated toxin, was dramatically reduced in the agrB mutant at both the transcriptional and protein levels, though not in a luxS mutant. Transwell assays confirmed that the Agrlike QS system controls NetB production through a diffusible signal. Global gene expression analysis of the agrB mutant identified additional genes modulated by Agrlike QS, including operons related to phospholipid metabolism and adherence, which may also play a role in NE pathogenesis. This study provides the first evidence that the Agr-like QS system is critical for NE pathogenesis and identifies a number of Agr-regulated genes, most notably netB, that are potentially involved in mediating its effects. The Agr-like QS system thus may serve as a target for developing novel interventions to prevent NE in chickens.KEYWORDS NetB, Clostridium perfringens, Agr-like quorum sensing, LuxS, VirS/VirR, necrotic enteritis, poultry, quorum sensing C lostridium perfringens is a Gram-positive, spore-forming, anaerobic bacterium that is widely distributed in soil, feces, and foods as well as the normal intestinal microbiota of both humans and animals (1). C. perfringens is responsible for a number of human and animal diseases owing to an arsenal of at least 16 different extracellular toxins, including food poisoning, gas gangrene in humans, enterotoxemia of sheep and goats, lamb dysentery, and necrotic enteritis (NE) in poultry (2). Strains are classified into five toxinotypes (A to E) based on the production of four major typing toxins (alpha-, beta-, epsilon-, and iota-toxin) (3, 4).Certain type A strains can produce NE, an enteric disease of poultry that, in 2015, was estimated to cost the worldwide poultry industry nearly $6 billion in losses (5). The disease occurs when C. perfringens proliferates to high numbers in the intestinal tract and produces extracellular toxins, resulting in characteristic necrotic lesions and often high rates of mortality (6, 7). In addition to producing alpha-toxin (CPA), which is carried

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Structural and biochemical characterization of Clostridium perfringens pili protein B collagen‐binding domains

et al. 2023

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Sortase‐mediated pili are flexible rod proteins composed of major and minor/tip pilins, playing important roles in the initial adhesion of bacterial cells to host tissues. The pilus shaft is formed by covalent polymerization of major pilins, and the minor/tip pilin is covalently attached to the tip of the shaft involved in adhesion to the host cell. The Gram‐positive bacterium Clostridium perfringens has a major pilin, and a minor/tip pilin (CppB) with the collagen‐binding motif. Here, we report X‐ray structures of CppB collagen‐binding domains, collagen‐binding assays and mutagenesis analysis, demonstrating that CppB collagen‐binding domains adopt an L‐shaped structure in open form, and that a small β‐sheet unique to CppB provides a scaffold for a favourable binding site for collagen peptide.

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Binding of Clostridium perfringens to collagen correlates with the ability to cause necrotic enteritis in chickens

Cited by 79 publications

References 24 publications

Genome analysis of Clostridium perfringens isolates from healthy and necrotic enteritis infected chickens and turkeys

Genome analysis of Clostridium perfringens isolates from healthy and necrotic enteritis infected chickens and turkeys

The Agr-Like Quorum Sensing System Is Required for Pathogenesis of Necrotic Enteritis Caused by Clostridium perfringens in Poultry

Structural and biochemical characterization of Clostridium perfringens pili protein B collagen‐binding domains

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