Nanobodies targeting conserved epitopes on the major outer membrane protein of Campylobacter as potential tools for control of Campylobacter colonization

Vanmarsenille, Charlotte; Olmo, InĂŠs DĂ­az del; Elseviers, Jelle; Ghassabeh, Gholamreza Hassanzadeh; Moonens, Kristof; Vertommen, Didier; Martel, An; Haesebrouck, Freddy; Pasmans, Frank; Hernálsteens, Jean-Pierre; Greve, Henri De

doi:10.1186/s13567-017-0491-9

Cited by 22 publications

(23 citation statements)

References 64 publications

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“…This VHH, directed against the flagella, can potently inhibit C. jejuni motility and is being studied for the prevention or significant reduction of C. jejuni colonization in the gastrointestinal tract of chickens. Recently Vanmarsenille et al [40] described the isolation and characterization of 6 VHHs against multiple Campylobacter strains. These VHHs which bind with the major outer membrane protein (MOMP) interacted with 23 C. jejuni isolates and 5 C. coli isolates.…”

Section: Campylobacteriosismentioning

confidence: 99%

Use of camel single-domain antibodies for the diagnosis and treatment of zoonotic diseases

Lafaye

2018

Comparative Immunology, Microbiology and Infectious Diseases

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A B S T R A C TCamelids produce both conventional heterotetrameric antibodies and homodimeric heavy-chain only antibodies. The antigen-binding region of such homodimeric heavy-chain only antibodies consists of one single domain, called VHH. VHHs provide many advantages over conventional full-sized antibodies and currently used antibody-based fragments (Fab, scFv), including high specificity, stability and solubility, and small size, allowing them to recognize unusual antigenic sites and deeply penetrate tissues. Since their discovery, VHHs have been used extensively in diagnostics and therapy. In recent decades, the number of outbreaks of diseases transmissible from animals to humans has been on the rise. In this review, we evaluate the status of VHHs as diagnostic and therapeutic biomolecular agents for the detection and treatment of zoonotic diseases, such as bacterial, parasitic, and viral zoonosis. VHHs show great adaptability to inhibit or neutralize pathogenic agents for the creation of multifunctional VHH-based diagnostic and therapeutic molecules against zoonotic diseases.

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Section: Campylobacteriosismentioning

confidence: 99%

Use of camel single-domain antibodies for the diagnosis and treatment of zoonotic diseases

Lafaye

2018

Comparative Immunology, Microbiology and Infectious Diseases

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“…Campylobacter jejuni is the most reported food-borne pathogen in human gastrointestinal infections over last decade [1]. C. jejuni are frequently found in the gastrointestinal tract of healthy animals that are destined for human consumption, especially chickens, which naturally harbour Campylobacter spp.…”

Section: Introductionmentioning

confidence: 99%

“…C. jejuni are frequently found in the gastrointestinal tract of healthy animals that are destined for human consumption, especially chickens, which naturally harbour Campylobacter spp. in their gastrointestinal tracts [1][2][3].…”

Section: Introductionmentioning

confidence: 99%

“…In particular, the control of Campylobacter spp. in poultry is the most important concern for consumers [1,9]. Importantly, this needs to be achieved without increased use of antibiotics and for that reason, alternative strategies for the reduction of colonisation of Campylobacter spp.…”

Section: Introductionmentioning

confidence: 99%

“…Several strategies with limited efficacy have been applied to reduce the burden of Campylobacter spp. in the intestine of pig and poultry including vaccination, passive immunisation, bacteriophage therapy, bacteriocin application, organic acids, and medium chain fatty acids [1,[9][10][11]. On the other hand, probiotic bacteria can have high affinity for adherence to the mucosal wall, where they promote the integrity of the healthy functioning of the gastrointestinal barrier by decreasing paracellular permeability through strengthening the tight junctions [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

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Effect of Lactobacillus spp. on adhesion, invasion, and translocation of Campylobacter jejuni in chicken and pig small-intestinal epithelial cell lines

et al. 2020

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Background: Campylobacter spp. are a major cause of bacterial food-borne diarrhoeal disease. This mainly arises through contamination of meat products during processing. For infection, Campylobacter spp. must adhere to epithelial cells of the mucus layer, survive conditions of the gastrointestinal tract, and colonise the intestine of the host. Addition of probiotic bacteria might promote competitive adhesion to epithelial cells, consequently reducing Campylobacter jejuni colonisation. Effect of Lactobacillus spp. (PCS20, PCS22, PCS25, LGG, PCK9) on C. jejuni adhesion, invasion and translocation in pig (PSI cl.1) and chicken (B1OXI) small-intestine cell lines, as well as pig enterocytes (CLAB) was investigated. Results: Overall, in competitive adhesion assays with PSI cl.1 and CLAB cell monolayers, the addition of Lactobacillus spp. reduced C. jejuni adherence to the cell surface, and negatively affected the C. jejuni invasion. Interestingly, Lactobacillus spp. significantly impaired C. jejuni adhesion in three-dimensional functional PSI cl.1 and B1OXI cell models. Also, C. jejuni did not translocate across PSI cl.1 and B1OXI cell monolayers when co-incubated with probiotics. Among selected probiotics, Lactobacillus rhamnosus LGG was the strain that reduced adhesion efficacy of C. jejuni most significantly under co-culture conditions. Conclusion: The addition of Lactobacillus spp. to feed additives in livestock nutrition might be an effective novel strategy that targets Campylobacter adhesion to epithelial cells, and thus prevents colonisation, reduces the transmission, and finally lowers the incidence of human campylobacteriosis.

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Recombinant Limosilactobacillus (Lactobacillus) delivering nanobodies against Clostridium perfringens NetB and alpha toxin confers potential protection from necrotic enteritis

Gangaiah

Ryan

Hoesel³

et al. 2022

MicrobiologyOpen

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Necrotic enteritis (NE), caused by Clostridium perfringens , is an intestinal disease with devastating economic losses to the poultry industry. NE is a complex disease and predisposing factors that compromise gut integrity are required to facilitate C. perfringens proliferation and toxin production. NE is also characterized by drastic shifts in gut microbiota; C. perfringens is negatively correlated with Lactobacilli. Vaccines are only partially effective against NE and antibiotics suffer from the concern of resistance development. These strategies address only some aspects of NE pathogenesis. Thus, there is an urgent need for alternative strategies that address multiple aspects of NE biology. Here, we developed Limosilactobacillus ( Lactobacillus ) reuteri vectors for in situ delivery of nanobodies against NetB and α toxin, two key toxins associated with NE pathophysiology. We generated nanobodies and showed that these nanobodies neutralize NetB and α toxin. We selected L. reuteri vector strains with intrinsic benefits and demonstrated that these strains inhibit C. perfringens and secrete over 130 metabolites, some of which play a key role in maintaining gut health. Recombinant L. reuteri strains efficiently secreted nanobodies and these nanobodies neutralized NetB. The recombinant strains were genetically and phenotypically stable over 480 generations and showed persistent colonization in chickens. A two‐dose in ovo and drinking water administration of recombinant L. reuteri strains protected chickens from NE‐associated mortality. These results provide proof‐of‐concept data for using L. reuteri as a live vector for delivery of nanobodies with broad applicability to other targets and highlight the potential synergistic effects of vector strains and nanobodies for addressing complex diseases such as NE.

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Nanobodies targeting conserved epitopes on the major outer membrane protein of Campylobacter as potential tools for control of Campylobacter colonization

Cited by 22 publications

References 64 publications

Use of camel single-domain antibodies for the diagnosis and treatment of zoonotic diseases

Use of camel single-domain antibodies for the diagnosis and treatment of zoonotic diseases

Effect of Lactobacillus spp. on adhesion, invasion, and translocation of Campylobacter jejuni in chicken and pig small-intestinal epithelial cell lines

Recombinant Limosilactobacillus (Lactobacillus) delivering nanobodies against Clostridium perfringens NetB and alpha toxin confers potential protection from necrotic enteritis

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