Toxin A-predominant Pathogenic C. difficile: A Novel Clinical Phenotype

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2019.

Lin Q, Pollock NR, Banz A, Lantz A, Xu H, Gu L, Gerding DN, Garey KW, Gonzales-Luna AJ, Zhao M, Song L, Duffy DC, Kelly CP and Chen X

Clin Infect Dis. 2019 Aug 11. pii: ciz727. doi: 10.1093/cid/ciz727.



Most Clostridioides difficile toxinogenic strains produce both toxins A and B (A+B+), but A-B+ variants also cause disease. We report the identification of a series of pathogenic clinical C. difficile isolates that produce high amounts of toxin A with low or non-detectable toxin B.


An ultrasensitive, quantitative immunoassay was used to measure toxins A and B in stools from 187 CDI patients and 44 carriers. Isolates were cultured and assessed for in vitro toxin production and in vivo phenotype (mouse CDI model).


7 CDI patients and 6 carriers had stools with detectable toxin A (range 23-17,422 pg/mL, 5.6% of samples overall) but toxin B below the clinical detection limit (<20 pg/mL; median TcdA:B ratio 17.93). Concentrations of toxin A far exceeded B in in vitro cultures of all 12 recovered isolates (median TcdA:B ratio 26). Of eight toxin A>>B isolates tested in mice, 4 caused diarrhea, and 3 of those 4 caused lethal disease. Ribotyping demonstrated strain diversity. TcdA-predominant samples were also identified at two other centers, with similar frequency (7.5% and 6.8%).


We report the discovery of clinical pathogenic C. difficile strains that produce high levels of toxin A but minimal or no toxin B. This pattern of toxin production is not rare (>5% of isolates) and is consistently observed in vitro and in vivo in humans and mice. Our study highlights the significance of toxin A in human CDI pathogenesis and has important implications for CDI diagnosis, treatment and vaccine development.

This website uses cookies. By continuing to use this website you are acknowledging and agree with our cookie policy.

AgreeLearn more