Effects of ciprofloxacin on the expression and production of exotoxins by Free

Abstract

Hypervirulent BI/NAP1/027 strains of have been associated with increased mortality of infection (CDI). The emergence of highly fluoroquinolone (FLQ)-resistant BI/NAP1/027 strains suggests that FLQ exposure may be a risk factor for CDI development. However, the mechanism for this is not clear. We compared the effects of subinhibitory concentrations of ciprofloxacin on Toxin A and B gene expression and protein production in recent (strain 039) and historical (strain 5325) BI/NAP1/027 clinical isolates with high- and low-level ciprofloxacin resistance, respectively. In the highly ciprofloxacin-resistant isolate (strain 039), ciprofloxacin significantly and dose-dependently increased Toxin A gene expression and shifted its expression to earlier in its growth cycle; TcdB gene expression also increased but was less sensitive to low-dose ciprofloxacin. Maximal Toxin A/B production (4 ng ml) was increased twofold and occurred significantly earlier than in the untreated control. In strain 5325, ciprofloxacin at 0.25×MIC markedly increased both and expression but their temporal dynamics were unchanged. Maximal toxin production (250 ng ml) was reduced approximately threefold compared with that of the untreated control. These results demonstrate significant differences in ciprofloxacin-induced toxin gene expression and protein production among BI/NAP1/027 isolates, and offer a new paradigm for FLQ-associated CDI caused by recent, highly antibiotic-resistant strains.

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.056218-0
2013-05-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jmm/62/5/741.html?itemId=/content/journal/jmm/10.1099/jmm.0.056218-0&mimeType=html&fmt=ahah

References

  1. Adams D. A., Riggs M. M., Donskey C. J. 2007; Effect of fluoroquinolone treatment on growth of and toxin production by epidemic and nonepidemic Clostridium difficile strains in the cecal contents of mice. Antimicrob Agents Chemother 51:2674–2678 [View Article][PubMed]
    [Google Scholar]
  2. Bartlett J. G. 1992; Antibiotic-associated diarrhea. Clin Infect Dis 15:573–581 [View Article][PubMed]
    [Google Scholar]
  3. Carter G. P., Douce G. R., Govind R., Howarth P. M., Mackin K. E., Spencer J., Buckley A. M., Antunes A., Kotsanas D. et al. 2011; The anti-sigma factor TcdC modulates hypervirulence in an epidemic BI/NAP1/027 clinical isolate of Clostridium difficile. PLoS Pathog 7:e1002317 [View Article][PubMed]
    [Google Scholar]
  4. CLSI (2004). Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria; Approved Standard, 6th ed. NCCLS document M11-A6. Wayne, PA: NCCLS
  5. Deshpande A., Pant C., Jain A., Fraser T. G., Rolston D. D. 2008; Do fluoroquinolones predispose patients to Clostridium difficile associated disease? A review of the evidence. Curr Med Res Opin 24:329–333 [View Article][PubMed]
    [Google Scholar]
  6. Dhalla I. A., Mamdani M. M., Simor A. E., Kopp A., Rochon P. A., Juurlink D. N. 2006; Are broad-spectrum fluoroquinolones more likely to cause Clostridium difficile-associated disease?. Antimicrob Agents Chemother 50:3216–3219 [View Article][PubMed]
    [Google Scholar]
  7. Drummond L. J., Smith D. G., Poxton I. R. 2003; Effects of sub-MIC concentrations of antibiotics on growth of and toxin production by Clostridium difficile. J Med Microbiol 52:1033–1038 [View Article][PubMed]
    [Google Scholar]
  8. Gerber M., Walch C., Loffler R., Tischendorf K., Reischl U., Ackermann G. 2008; Effect of sub-MIC concentrations of metronidazole, vancomycin, clindamycin and linzolid on toxin gene transcription and production in Clostridium difficile. J Med Microbiol 57:776–783 [View Article]
    [Google Scholar]
  9. Honda T., Hernadez I., Katoh T., Miwatani T. 1983; Stimulation of enterotoxin production of Clostridium difficile by antibiotics. Lancet 321:655 [View Article][PubMed]
    [Google Scholar]
  10. Hookman P., Barkin J. S. 2009; Clostridium difficile associated infection, diarrhea and colitis. World J Gastroenterol 15:1554–1580 [View Article][PubMed]
    [Google Scholar]
  11. Livak K. J., Schmittgen T. D. 2001; Analysis of relative gene expression data using real-time quantitative PCR and the 2–ΔΔT method. Methods 25:402–408 [View Article][PubMed]
    [Google Scholar]
  12. McFarland L. V., Clarridge J. E., Beneda H. W., Raugi G. J. 2007; Fluoroquinolone use and risk factors for Clostridium difficile-associated disease within a Veterans Administration health care system. Clin Infect Dis 45:1141–1151 [View Article][PubMed]
    [Google Scholar]
  13. Merrigan M., Venugopal A., Mallozzi M., Roxas B., Viswanathan V. K., Johnson S., Gerding D. N., Vedantam G. 2010; Human hypervirulent Clostridium difficile strains exhibit increased sporulation as well as robust toxin production. J Bacteriol 192:4904–4911 [View Article][PubMed]
    [Google Scholar]
  14. Novell M. J., Morreale C. A. 2010; The relationship between inpatient fluoroquinolone use and Clostridium difficile-associated diarrhea. Ann Pharmacother 44:826–831 [View Article][PubMed]
    [Google Scholar]
  15. O’Connor J. R., Johnson S., Gerding D. N. 2009; Clostridium difficile infection caused by the epidemic B1/NAP1/027 strain. Gastroenterology 136:1913–1924 [View Article]
    [Google Scholar]
  16. Onderdonk A. B., Lowe B. R., Bartlett J. G. 1979; Effect of environmental stress on Clostridium difficile toxin levels during continuous cultivation. Appl Environ Microbiol 38:637–641[PubMed]
    [Google Scholar]
  17. Pultz N. J., Donskey C. J. 2005; Effect of antibiotic treatment on growth of and toxin production by Clostridium difficile in the cecal contents of mice. Antimicrob Agents Chemother 49:3529–3532 [View Article][PubMed]
    [Google Scholar]
  18. Ruiz J. 2003; Mechanisms of resistance to quinolones: target alterations, decreased accumulation and DNA gyrase protection. J Antimicrob Chemother 51:1109–1117 [View Article][PubMed]
    [Google Scholar]
  19. Saxton K., Baines S. D., Freeman J., O’Connor R., Wilcox M. H. 2009; Effects of exposure of Clostridium difficile PCR ribotypes 027 and 001 to fluoroquinolones in a human gut model. Antimicrob Agents Chemother 53:412–420 [View Article][PubMed]
    [Google Scholar]
  20. Stevens D. L., Ma Y., Salmi D. B., McIndoo E., Wallace R. J., Bryant A. E. 2007; Impact of antibiotics on expression of virulence-associated exotoxin genes in methicillin-sensitive and methicillin-resistant Staphylococcus aureus. J Infect Dis 195:202–211 [View Article][PubMed]
    [Google Scholar]
  21. Tan K. S., Wee B. Y., Song K. P. 2001; Evidence for holin function of tcdE gene in the pathogenicity of Clostridium difficile. J Med Microbiol 50:613–619[PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.056218-0
Loading
/content/journal/jmm/10.1099/jmm.0.056218-0
Loading

Data & Media loading...

Most cited Most Cited RSS feed