Absence of Toxin Gene Transfer from Clostridioides Difficile Strain 630Δerm to Nontoxigenic C. Difficile Strain NTCD-M3r in Filter Mating Experiments

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2022 Jun 29

PMID 35767545

Authors

Susan P Sambol

Stuart Johnson

Adam Cheknis

Dale N Gerding

Affiliations

Soon will be listed here.

Abstract

Nontoxigenic Clostridioides difficile strain M3 (NTCD-M3) protects hamsters and humans against C. difficile infection. Transfer in vitro of the pathogenicity locus (PaLoc) to nontoxigenic strain CD37 has been reported. We repeated these conjugations using toxigenic strain 630Δerm as donor and NTCD-M3 and CD37 as recipients. In order to conduct these matings we induced rifampin resistance (50ug/ml) in NTCD-M3 by serial passage on rifampin-containing media to obtain strain NTCD-M3r. 630Δerm/CD37 matings produced 21 PaLoc transconjugants in 5.5 x 109 recipient CFUs; a frequency of 3.8 x 10-9. All transconjugants carried the tcdB gene and produced toxin. 630Δerm/NTCD-M3r matings produced no transconjugants in 5 assays with a total of 9.4 x 109 NTCD-M3r recipient cells. Toxin gene transfer to NTCD-M3r could not be demonstrated under conditions that demonstrated transfer to strain CD37.

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References

Shim J, Johnson S, Samore M, Bliss D, Gerding D . Primary symptomless colonisation by Clostridium difficile and decreased risk of subsequent diarrhoea. Lancet. 1998; 351(9103):633-6. DOI: 10.1016/S0140-6736(97)08062-8. View

Minton N, Ehsaan M, Humphreys C, Little G, Baker J, Henstra A . A roadmap for gene system development in Clostridium. Anaerobe. 2016; 41:104-112. PMC: 5058259. DOI: 10.1016/j.anaerobe.2016.05.011. View

Seal D, Borriello S, Barclay F, Welch A, Piper M, Bonnycastle M . Treatment of relapsing Clostridium difficile diarrhoea by administration of a non-toxigenic strain. Eur J Clin Microbiol. 1987; 6(1):51-3. DOI: 10.1007/BF02097191. View

Johnson S . Recurrent Clostridium difficile infection: a review of risk factors, treatments, and outcomes. J Infect. 2009; 58(6):403-10. DOI: 10.1016/j.jinf.2009.03.010. View

Sambol S, Merrigan M, Tang J, Johnson S, Gerding D . Colonization for the prevention of Clostridium difficile disease in hamsters. J Infect Dis. 2002; 186(12):1781-9. DOI: 10.1086/345676. View

Couturier J, Franconeri L, Janoir C, Ferraris L, Syed-Zaidi R, Youssouf A . Characterization of Non-Toxigenic Strains Isolated from Preterm Neonates and In Vivo Study of Their Protective Effect. J Clin Med. 2020; 9(11). PMC: 7696784. DOI: 10.3390/jcm9113650. View

Wang Y, Wang S, Bouillaut L, Li C, Duan Z, Zhang K . Oral Immunization with Nontoxigenic Clostridium difficile Strains Expressing Chimeric Fragments of TcdA and TcdB Elicits Protective Immunity against C. difficile Infection in Both Mice and Hamsters. Infect Immun. 2018; 86(11). PMC: 6204701. DOI: 10.1128/IAI.00489-18. View

Gerding D, Meyer T, Lee C, Cohen S, Murthy U, Poirier A . Administration of spores of nontoxigenic Clostridium difficile strain M3 for prevention of recurrent C. difficile infection: a randomized clinical trial. JAMA. 2015; 313(17):1719-27. DOI: 10.1001/jama.2015.3725. View

Brouwer M, Roberts A, Hussain H, Williams R, Allan E, Mullany P . Horizontal gene transfer converts non-toxigenic Clostridium difficile strains into toxin producers. Nat Commun. 2013; 4:2601. PMC: 3826655. DOI: 10.1038/ncomms3601. View

10.

Merrigan M, Venugopal A, Roxas J, Anwar F, Mallozzi M, Roxas B . Surface-layer protein A (SlpA) is a major contributor to host-cell adherence of Clostridium difficile. PLoS One. 2013; 8(11):e78404. PMC: 3827033. DOI: 10.1371/journal.pone.0078404. View

11.

Clabots C, Johnson S, Bettin K, Mathie P, Mulligan M, Schaberg D . Development of a rapid and efficient restriction endonuclease analysis typing system for Clostridium difficile and correlation with other typing systems. J Clin Microbiol. 1993; 31(7):1870-5. PMC: 265648. DOI: 10.1128/jcm.31.7.1870-1875.1993. View

12.

Griffiths D, Fawley W, Kachrimanidou M, Bowden R, Crook D, Fung R . Multilocus sequence typing of Clostridium difficile. J Clin Microbiol. 2010; 48(3):770-8. PMC: 2832416. DOI: 10.1128/JCM.01796-09. View

13.

Oliveira Junior C, Silva R, Cruz D, Pires I, Guedes R, Lobato F . The non-toxigenic strain of Clostridioides difficile Z31 can prevent infection by C. difficile in experimental model piglets. Anaerobe. 2018; 55:24-28. DOI: 10.1016/j.anaerobe.2018.10.002. View

14.

Sambol S, Tang J, Merrigan M, Johnson S, Gerding D . Infection of hamsters with epidemiologically important strains of Clostridium difficile. J Infect Dis. 2001; 183(12):1760-6. DOI: 10.1086/320736. View

15.

Gerding D, Kelly C, Rahav G, Lee C, Dubberke E, Kumar P . Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection in Patients at Increased Risk for Recurrence. Clin Infect Dis. 2018; 67(5):649-656. PMC: 6093994. DOI: 10.1093/cid/ciy171. View

16.

Borriello S, Barclay F . Protection of hamsters against Clostridium difficile ileocaecitis by prior colonisation with non-pathogenic strains. J Med Microbiol. 1985; 19(3):339-50. DOI: 10.1099/00222615-19-3-339. View

17.

Lessa F, Mu Y, Bamberg W, Beldavs Z, Dumyati G, Dunn J . Burden of Clostridium difficile infection in the United States. N Engl J Med. 2015; 372(9):825-34. PMC: 10966662. DOI: 10.1056/NEJMoa1408913. View

18.

Guh A, Mu Y, Winston L, Johnston H, Olson D, Farley M . Trends in U.S. Burden of Infection and Outcomes. N Engl J Med. 2020; 382(14):1320-1330. PMC: 7861882. DOI: 10.1056/NEJMoa1910215. View