Effects of surotomycin on Clostridium difficile viability and toxin production in vitro.
The increasing incidence and severity of infection by Clostridium difficile have stimulated attempts to develop new antimicrobial therapies. We report here the relative abilities of two antibiotics (metronidazole and vancomycin) in current use for treating C. difficile infection and of a third antimicrobial, surotomycin, to kill C. difficile cells at various stages of development and to inhibit the production of the toxin proteins that are the major virulence factors. The results indicate that none of the drugs affects the viability of spores at 8× MIC or 80× MIC and that all of the drugs kill exponential-phase cells when provided at 8× MIC. In contrast, none of the drugs killed stationary-phase cells or inhibited toxin production when provided at 8× MIC and neither vancomycin nor metronidazole killed stationary-phase cells when provided at 80× MIC. Surotomycin, on the other hand, did kill stationary-phase cells when provided at 80× MIC but did so without inducing lysis.
Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, USA.
Laurent
L
Bouillaut
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA Emory Antibiotic Resistance Center, Emory University School of Medicine, Atlanta, Georgia, USA.
Shonna
S
McBride
Department of Biology, Texas A&M University, College Station, Texas, USA.
Joseph A
http://orcid.org/0000-0001-7822-2656
JA
Sorg
Department of Infectious Disease and Global Health, Tufts University Cummings School of Veterinary Medicine, North Grafton, Massachusetts, USA.
Diane J
DJ
Schmidt
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA.
José M
JM
Suarez
Department of Infectious Disease and Global Health, Tufts University Cummings School of Veterinary Medicine, North Grafton, Massachusetts, USA.
Saul
S
Tzipori
Cubist Pharmaceuticals, Lexington, Massachusetts, USA.
Carmela
C
Mascio
Cubist Pharmaceuticals, Lexington, Massachusetts, USA.
Laurent
L
Chesnel
Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, USA linc.sonenshein@tufts.edu.
A L
AL
Sonenshein
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001427:Bacterial Toxins / Q000096:biosynthesis* / Q000235:genetics; D002473:Cell Wall / Q000187:drug effects; D016360:Clostridioides difficile / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D004768:Enterotoxins / Q000096:biosynthesis* / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D055666:Lipopeptides / Q000494:pharmacology*; D008795:Metronidazole / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009154:Mutation / Q000235:genetics; D010456:Peptides, Cyclic / Q000494:pharmacology*; D013171:Spores, Bacterial / Q000187:drug effects; D014640:Vancomycin / Q000494:pharmacology; D037521:Virulence Factors / Q000378:metabolism
D000900:Anti-Bacterial Agents; D001427:Bacterial Toxins; C574454:CB-183,315; D004768:Enterotoxins; D055666:Lipopeptides; D010456:Peptides, Cyclic; D037521:Virulence Factors; C041348:tcdA protein, Clostridium difficile; D008795:Metronidazole; D014640:Vancomycin