Expression of virulence factors of Clostridioides difficile at sub-minimum inhibitory concentration of antibiotics

A review

https://doi.org/10.53730/ijhs.v6nS10.13883

Authors

  • Hamid Hakimi Immunology of Infectious Diseases Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran|Department of Microbiology, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
  • Shokrollah Assar Immunology of Infectious Diseases Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran|Department of Microbiology, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
  • Mitra Abbasifard Immunology of Infectious Diseases Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran|Department of Internal Medicine, Ali-Ibn Abi-Talib Hospital, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
  • Seyed-Mehdi Mousavi Department of Microbiology, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
  • Reza Bahramabadi Immunology of Infectious Diseases Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran|Department of Microbiology, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
  • Mohammad Taheri Department of Microbiology, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
  • Siavash Assar Department of Anesthesiology, Medical School, Kerman University of Medical Sciences, Kerman, Iran
  • Hasan Ebrahimi Shahmabadi Department of Microbiology, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
  • Ebrahim Rezazadeh Zarandi Immunology of Infectious Diseases Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran|Department of Microbiology, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran

Keywords:

virulence factors, sub-MIC, clostridioides difficile, antibiotics, gene expression

Abstract

Clostridioides difficile (C. difficile) generally colonizes in the colon of hospitalized patients who receive antibiotics for a long time. C. difficile expresses its virulence factors which are associated with pathogenesis. Naturally, the expression of these virulence factors may be influenced by antibiotics. The effect of antibiotics at the sub-minimum inhibitory concentration (MIC) on virulence factors has been investigated and it is varied and depends on the type of antibiotic and C. difficile isolate. Some of the antibiotics at sub-MIC upregulate virulence factors, while others downregulate. Meanwhile, some antibiotics have no detectable effects on the regulation of virulence factors. Nearly, all investigations have surveyed a few numbers of C. difficile isolates in terms the expression of virulence factors at sub-MIC. Most of the antibiotics at sub-MICs regulate gene expression of virulence factors, toxin production, spore formation, and germination by several mechanisms especially the SOS response system. However, to achieve a clear understanding of the effect of antibiotics at sub-MIC on the expression of genes of virulence factors, which are related to the pathogenesis of C. difficile, further and wider investigations are needed, especially on the issue of the numbers of isolates that have been discussed in the present review article.

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References

Lawson PA, Citron DM, Tyrrell KL, Finegold SM. Reclassification of Clostridium difficile as Clostridioides difficile (Hall and O’Toole 1935) Prévot 1938. Anaerobe. 2016;40:95-9.

Bartlett JG. Clostridium difficile Infection. Infect Dis Clin North Am. 2017;31(3):489-95.

Lessa FC, Mu Y, Bamberg WM, Beldavs ZG, Dumyati GK, Dunn JR, et al. Burden of Clostridium difficile infection in the United States. New England Journal of Medicine. 2015;372(9):825-34.

Dantes R, Mu Y, Hicks LA, Cohen J, Bamberg W, Beldavs ZG, et al., editors. Association between outpatient antibiotic prescribing practices and community-associated Clostridium difficile infection. Open forum infectious diseases; 2015: Oxford University Press.

Cho SM, Lee JJ, Yoon HJ. Clinical risk factors for Clostridium difficile-associated diseases. The Brazilian Journal of Infectious Diseases. 2012;16(3):256-61.

Willing SE, Richards EJ, Sempere L, Dale AG, Cutting SM, Fairweather NF. Increased toxin expression in a Clostridium difficile mfd mutant. BMC Microbiol. 2015;15(280):280.

Nakamura S, Mikawa M, Tanabe N, Yamakawa K, Nishida S. Effect of clindamycin on cytotoxin production by Clostridium difficile. Microbiology and immunology. 1982;26(11):985-92.

Davies J, Spiegelman GB, Yim G. The world of subinhibitory antibiotic concentrations. Current opinion in microbiology. 2006;9(5):445-53.

Bader MW, Navarre WW, Shiau W, Nikaido H, Frye JG, McClelland M, et al. Regulation of Salmonella typhimurium virulence gene expression by cationic antimicrobial peptides. Molecular microbiology. 2003;50(1):219-30.

Goh E-B, Yim G, Tsui W, McClure J, Surette MG, Davies J. Transcriptional modulation of bacterial gene expression by subinhibitory concentrations of antibiotics. Proceedings of the National Academy of Sciences. 2002;99(26):17025-30.

Bagge N, Schuster M, Hentzer M, Ciofu O, Givskov M, Greenberg EP, et al. Pseudomonas aeruginosa biofilms exposed to imipenem exhibit changes in global gene expression and β-lactamase and alginate production. Antimicrobial agents and chemotherapy. 2004;48(4):1175-87.

Kheir MM, Tan TL, Azboy I, Tan DD, Parvizi J. Vancomycin prophylaxis for total joint arthroplasty: Incorrectly dosed and has a higher rate of periprosthetic infection than cefazolin. Clinical Orthopaedics and Related Research®. 2017:1-8.

Hung Y-P, Lee J-C, Lin H-J, Chiu C-W, Wu J-L, Liu H-C, et al. Perceptions of Clostridium difficile infections among infection control professionals in Taiwan. Journal of Microbiology, Immunology and Infection. 2017.

Deneve C, Bouttier S, Dupuy B, Barbut F, Collignon A, Janoir C. Effects of subinhibitory concentrations of antibiotics on colonization factor expression by moxifloxacin-susceptible and moxifloxacin-resistant Clostridium difficile strains. Antimicrob Agents Chemother. 2009;53(12):5155-62.

Drummond LJ, Smith DG, Poxton IR. Effects of sub-MIC concentrations of antibiotics on growth of and toxin production by Clostridium difficile. J Med Microbiol. 2003;52(Pt 12):1033-8.

Bouillaut L, McBride S, Sorg JA, Schmidt DJ, Suarez JM, Tzipori S, et al. Effects of surotomycin on Clostridium difficile viability and toxin production in vitro. Antimicrobial agents and chemotherapy. 2015;59(7):4199-205.

Babakhani F, Bouillaut L, Sears P, Sims C, Gomez A, Sonenshein AL. Fidaxomicin inhibits toxin production in Clostridium difficile. J Antimicrob Chemother. 2013;68(3):515-22.

Bassères E, Endres BT, Khaleduzzaman M, Miraftabi F, Alam MJ, Vickers RJ, et al. Impact on toxin production and cell morphology in Clostridium difficile by ridinilazole (SMT19969), a novel treatment for C. difficile infection. Journal of Antimicrobial Chemotherapy. 2016;71(5):1245-51.

Endres BT, Bassères E, Khaleduzzaman M, Alam MJ, Chesnel L, Garey KW. Evaluating the effects of surotomycin treatment on Clostridium difficile toxin A and B production, immune response, and morphological changes. Antimicrobial agents and chemotherapy. 2016;60(6):3519-23.

Zarandi ER, Mansouri S, Nakhaee N, Sarafzadeh F, Moradi M. Toxin production of Clostridium difficile in sub-MIC of vancomycin and clindamycin alone and in combination with ceftazidime. Microbial pathogenesis. 2017;107:249-53.

Aldape MJ, Heeney DD, Bryant AE, Stevens DL. Tigecycline suppresses toxin A and B production and sporulation in Clostridium difficile. J Antimicrob Chemother. 2015;70(1):153-9.

Gerber M, Walch C, Loffler B, Tischendorf K, Reischl U, Ackermann G. Effect of sub-MIC concentrations of metronidazole, vancomycin, clindamycin and linezolid on toxin gene transcription and production in Clostridium difficile. J Med Microbiol. 2008;57(Pt 6):776-83.

Onderdonk AB, Lowe BR, Bartlett JG. Effect of environmental stress on Clostridium difficile toxin levels during continuous cultivation. Appl Environ Microbiol. 1979;38(4):637-41.

Zarandi ER, Mansouri S, Nakhaee N, Sarafzadeh F, Iranmanesh Z, Moradi M. Frequency of antibiotic associated diarrhea caused by Clostridium difficile among hospitalized patients in intensive care unit, Kerman, Iran. Gastroenterology and hepatology from bed to bench. 2017;10(3):229.

Babakhani F, Bouillaut L, Gomez A, Sears P, Nguyen L, Sonenshein AL. Fidaxomicin inhibits spore production in Clostridium difficile. Clin Infect Dis. 2012;55 Suppl 2(2):S162-9.

Garneau JR, Valiquette L, Fortier LC. Prevention of Clostridium difficile spore formation by sub-inhibitory concentrations of tigecycline and piperacillin/tazobactam. BMC Infect Dis. 2014;14(29):29.

Zar FA, Bakkanagari SR, Moorthi K, Davis MB. A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile–associated diarrhea, stratified by disease severity. Clinical Infectious Diseases. 2007;45(3):302-7.

Baines SD, Freeman J, Wilcox MH. Effects of piperacillin/tazobactam on Clostridium difficile growth and toxin production in a human gut model. Journal of Antimicrobial Chemotherapy. 2005;55(6):974-82.

Manthey C, Eckmann L, Fuhrmann V. Therapy for Clostridium difficile infection–any news beyond Metronidazole and Vancomycin? Expert Review of Clinical Pharmacology. 2017(just-accepted).

Fehér C, Rubio EM, Amador PM, Garcia-Campero AD-I, Salavert M, Merino E, et al. The efficacy of fidaxomicin in the treatment of Clostridium difficile infection in a real-world clinical setting: a Spanish multi-centre retrospective cohort. European Journal of Clinical Microbiology & Infectious Diseases. 2017;36(2):295-303.

Wu W-x, Liu D, Wang Y-w, Wang C, Yang C, Liu X-z, et al. Empirical Antibiotic Treatment in Diabetic Foot Infection: A Study Focusing on the Culture and Antibiotic Sensitivity in a Population From Southern China. The International Journal of Lower Extremity Wounds. 2017:1534734617725410.

Abraham P, Lamba N, Acosta M, Gholmie J, Dawood HY, Vestal M, et al. Antibacterial prophylaxis for gram-positive and gram-negative infections in cranial surgery: A meta-analysis. Journal of Clinical Neuroscience. 2017.

Khanafer N, Vanhems P, Barbut F, Luxemburger C, group CS. Factors associated with Clostridium difficile infection: A nested case-control study in a three year prospective cohort. Anaerobe. 2017;44:117-23.

Freeman J, O’neill FJ, Wilcox MH. Effects of cefotaxime and desacetylcefotaxime upon Clostridium difficile proliferation and toxin production in a triple-stage chemostat model of the human gut. Journal of Antimicrobial Chemotherapy. 2003;52(1):96-102.

Santos A, Isidro J, Silva C, Boaventura L, Diogo J, Faustino A, et al. Molecular and epidemiologic study of Clostridium difficile reveals unusual heterogeneity in clinical strains circulating in different regions in Portugal. Clinical Microbiology and Infection. 2016;22(8):695-700.

Aldape MJ, Packham AE, Nute DW, Bryant AE, Stevens DL. Effects of ciprofloxacin on the expression and production of exotoxins by Clostridium difficile. J Med Microbiol. 2013;62(Pt 5):741-7.

Karlsson S, Dupuy B, Mukherjee K, Norin E, Burman LG, Åkerlund T. Expression of Clostridium difficile toxins A and B and their sigma factor TcdD is controlled by temperature. Infection and immunity. 2003;71(4):1784-93.

Chilton C, Freeman J, Baines SD, Crowther G, Nicholson S, Wilcox M. Evaluation of the effect of oritavancin on Clostridium difficile spore germination, outgrowth and recovery. Journal of Antimicrobial Chemotherapy. 2013;68(9):2078-82.

Balsells E, Shi T, Leese C, Lyell I, Burrows J, Wiuff C, et al. Global burden of Clostridium difficile infections: a systematic review and meta-analysis. Journal of global health. 2019;9(1).

Czepiel J, Dróżdż M, Pituch H, Kuijper EJ, Perucki W, Mielimonka A, et al. Clostridium difficile infection. European Journal of Clinical Microbiology & Infectious Diseases. 2019:1-11.

Zarandi ER, Mansouri S, Nakhaee N, Sarafzadeh F, Moradi M. Effect of sub-MIC of vancomycin and clindamycin alone and in combination with ceftazidime on Clostridium difficile surface layer protein A (slpA) gene expression. Microbial pathogenesis. 2017;111:163-7.

Baines SD, Saxton K, Freeman J, Wilcox MH. Tigecycline does not induce proliferation or cytotoxin production by epidemic Clostridium difficile strains in a human gut model. J Antimicrob Chemother. 2006;58(5):1062-5.

Deneve C, Delomenie C, Barc MC, Collignon A, Janoir C. Antibiotics involved in Clostridium difficile-associated disease increase colonization factor gene expression. J Med Microbiol. 2008;57(Pt 6):732-8.

Dineen SS, Villapakkam AC, Nordman JT, Sonenshein AL. Repression of Clostridium difficile toxin gene expression by CodY. Molecular microbiology. 2007;66(1):206-19.

Published

18-12-2022

How to Cite

Hakimi, H., Assar, S., Abbasifard, M., Mousavi, S.-M., Bahramabadi, R., Taheri, M., Assar, S., Shahmabadi, H. E., & Zarandi, E. R. (2022). Expression of virulence factors of Clostridioides difficile at sub-minimum inhibitory concentration of antibiotics: A review. International Journal of Health Sciences, 6(S10), 1204–1214. https://doi.org/10.53730/ijhs.v6nS10.13883

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Section

Peer Review Articles