EurekaMag.com logo
+ Site Statistics
References:
53,869,633
Abstracts:
29,686,251
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on LinkedInFollow on LinkedIn

+ Translate

Antibody against TcdB, but not TcdA, prevents development of gastrointestinal and systemic Clostridium difficile disease



Antibody against TcdB, but not TcdA, prevents development of gastrointestinal and systemic Clostridium difficile disease



Journal of Infectious Diseases 207(2): 323-330



A dramatic increase in morbidity and mortality from Clostridium difficile infection (CDI) due to the recent emergence of virulent, antibiotic-resistant strains has led to a search for alternatives to antibiotics, including vaccines and immune-based therapy that target the 2 key toxins-TcdA and TcdB. We investigated the efficacy of specific human monoclonal antibodies (HuMab) and alpaca polyclonal antibodies against each toxin separately and in combination in the gnotobiotic piglet model of CDI. Additionally, the HuMab and polyclonal antibodies were exploited to investigate the precise contribution of each toxin to systemic and/or gastrointestinal (GI) tract disease. Our results indicate that TcdB is an important virulence factor associated with GI and systemic pathology. Administration of anti-TcdB antibody alone or with anti-TcdA protected 100% of piglets from development of systemic CDI and minimized GI lesions. Conversely, 100% of piglets administered only anti-TcdA developed severe GI and systemic disease, with 67%–83% fatality, faring worse than placebo-treated control animals. These results highlight the importance of TcdB in the pathogenesis of CDI and the effectiveness of TcdB-specific antibody in treating CDI. However, the results raise new questions regarding the nature of TcdA interaction with therapeutic antibodies.

(PDF emailed within 0-6 h: $19.90)

Accession: 036689828

Download citation: RISBibTeXText

PMID: 23125448

DOI: 10.1093/infdis/jis669



Related references

Defining the Roles of TcdA and TcdB in Localized Gastrointestinal Disease, Systemic Organ Damage, and the Host Response during Clostridium difficile Infections. Mbio 6(3): E00551-E00551, 2016

A novel multivalent, single-domain antibody targeting TcdA and TcdB prevents fulminant Clostridium difficile infection in mice. Journal of Infectious Diseases 210(6): 964-972, 2014

Sequence variation in tcdA and tcdB of Clostridium difficile: ST37 with truncated tcdA is a potential epidemic strain in China. Journal of Clinical Microbiology 52(9): 3264-3270, 2015

Intravenous adenovirus expressing a multi-specific, single-domain antibody neutralizing TcdA and TcdB protects mice from Clostridium difficile infection. Pathogens and Disease 74(7): -, 2017

Comparison of VIDAS CDAB and CDA immunoassay for the detection of Clostridium difficile in a tcdA- tcdB+ C. difficile prevalent area. Anaerobe 15(6): 266-269, 2010

Multi-hospital outbreak of Clostridium difficile associated disease mediated by ermB+/tcdA+/tcdB+ epidemic clone Observations following the restriction of clindamycin. Abstracts of the Interscience Conference on Antimicrobial Agents & Chemotherapy 43: 366, 2003

CdtR Regulates TcdA and TcdB Production in Clostridium difficile. Plos Pathogens 12(7): E1005758-E1005758, 2017

Lectin activity of the TcdA and TcdB toxins of Clostridium difficile. Infection and Immunity 2018, 2018

Detection and transcriptional analysis of tcdA and tcdB in a non-toxigenic strain of Clostridium difficile. Abstracts of the General Meeting of the American Society for Microbiology 99: 45-46, 1999

A DNA vaccine targeting TcdA and TcdB induces protective immunity against Clostridium difficile. Bmc Infectious Diseases 16(1): 596-596, 2016

Clostridium difficile Toxins TcdA and TcdB Cause Colonic Tissue Damage by Distinct Mechanisms. Infection and Immunity 84(10): 2871-2877, 2017

Release of TcdA and TcdB from Clostridium difficile cdi 630 is not affected by functional inactivation of the tcdE gene. Microbial Pathogenesis 52(1): 92-100, 2012

Multiplex PCR method for detection of Clostridium difficile tcdA, tcdB, cdtA, and cdtB and internal in-frame deletion of tcdC. Journal of Clinical Microbiology 49(12): 4299-4300, 2012

Overexpression of the Endosomal Anion/Proton Exchanger ClC-5 Increases Cell Susceptibility toward Clostridium difficile Toxins TcdA and TcdB. Frontiers in Cellular and Infection Microbiology 7: 67-67, 2017

Study of the frequency of Clostridium difficile tcdA, tcdB, cdtA and cdtB genes in feces of Calves in south west of Iran. Annals of Clinical Microbiology and Antimicrobials 13(): 21-21, 2014