title: Tigecycline suppresses toxin A and B production and sporulation in Clostridium difficile.
abstract: BACKGROUND
  Clostridium difficile infection (CDI) is mediated by potent extracellular toxins and is spread largely via bacterial spores. We and others have shown that some antibiotics stimulate C. difficile toxin production in a strain-specific manner; however, the effects of newer anti-C. difficile antibiotics on this process remain to be investigated.
  
  
  METHODS
  The effects of the protein synthesis inhibitor tigecycline on sporulation and toxin A and toxin B production were compared in historical (strain 9689) and hypervirulent BI/NAP1/027 (strain 5325) isolates of C. difficile in vitro.
  
  
  RESULTS
  Tigecycline at 1/4× MIC stimulated an increased and earlier toxin A and/or B gene expression in both the historical and the hypervirulent strains, although a commensurate increase in toxin protein production was observed only in the 9689 strain. In fact, in the hypervirulent 5325 strain, toxin production was dramatically suppressed. By comparison, subinhibitory concentrations of vancomycin and metronidazole also stimulated increased protein toxin production by the historical, but not the hypervirulent, strain. In addition, tigecycline dose-dependently reduced viable spore production by both the 9689 and 5325 strains. Vancomycin treatment also suppressed spore formation in both C. difficile strains; however, metronidazole, while reducing spore formation in the 9689 strain, stimulated a near 2 log increase in spore production by the 5325 isolate.
  
  
  CONCLUSIONS
  In summary, these findings suggest that the treatment of CDI patients with tigecycline could effectively both control disease progression and limit its spread by disrupting sporulation.
authors.affiliation: Department of Veterans Affairs Medical Center, 500 W. Fort Street, Boise, ID 83702, USA mike.aldape@va.gov.
authors.forename: Michael John
authors.initials: MJ
authors.lastname: Aldape
authors.affiliation: Department of Veterans Affairs Medical Center, 500 W. Fort Street, Boise, ID 83702, USA.
authors.forename: Dustin Delaney
authors.initials: DD
authors.lastname: Heeney
authors.affiliation: Department of Veterans Affairs Medical Center, 500 W. Fort Street, Boise, ID 83702, USA University of Washington School of Medicine, 1959 NE Pacific Street, Seattle, WA 98195, USA.
authors.forename: Amy Evelyn
authors.initials: AE
authors.lastname: Bryant
authors.affiliation: Department of Veterans Affairs Medical Center, 500 W. Fort Street, Boise, ID 83702, USA University of Washington School of Medicine, 1959 NE Pacific Street, Seattle, WA 98195, USA.
authors.forename: Dennis Leroy
authors.initials: DL
authors.lastname: Stevens
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors*; D016360:Clostridioides difficile / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D004768:Enterotoxins / Q000037:antagonists & inhibitors*; D006801:Humans; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000031:analogs & derivatives* / Q000494:pharmacology; D013171:Spores, Bacterial / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D000078304:Tigecycline
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004768:Enterotoxins; C041348:tcdA protein, Clostridium difficile; C031815:toxB protein, Clostridium difficile; D000078304:Tigecycline; D008911:Minocycline
keywords: antibiotics; human disease; infectious diseases; pathogenic bacteria