title: Ciprofloxacin induces mutagenesis to antibiotic resistance independent of UmuC in Streptococcus uberis.
abstract: Streptococcus uberis is an environmental bovine mastitis pathogen capable of UV-inducible SOS mutagenesis. Bacterial SOS systems can be induced by several chemicals including also antibiotics used in clinical practice. Here, we have studied the effect of ciprofloxacin, a fluoroquinolone antibiotic and known inducer of SOS, on mutations leading to antibiotic resistance in S. uberis. Mutation frequencies and spectra were compared in a wild-type S. uberis strain and its DeltaumuC derivative. The results revealed that concentrations of ciprofloxacin corresponding to 0.3-0.5x minimum inhibitory concentration (MIC) induce mutagenesis independent of UmuC. Partial sequencing of the rpoB gene of individual rifampin-resistant clones from wild-type and DeltaumuC strains revealed a similar but complex pattern of point mutations including transitions, transversions and deletions/insertions. It was previously shown that UV induces mainly transition-type mutations and UmuC is essential for the process. Thus, the results presented here demonstrate that S. uberis employs distinct mechanisms for ciprofloxacin and UV-induced mutagenesis, which is a striking difference to Escherichia coli SOS model.
authors.affiliation: University of Helsinki, Department of Basic Veterinary Sciences, PO Box 66, FIN-00014, Helsinki, Finland.
authors.forename: Emilia
authors.initials: E
authors.lastname: Varhimo
authors.forename: Kirsi
authors.initials: K
authors.lastname: Savijoki
authors.forename: Hanna
authors.initials: H
authors.lastname: Jefremoff
authors.forename: Jari
authors.initials: J
authors.lastname: Jalava
authors.forename: Antti
authors.initials: A
authors.lastname: Sukura
authors.forename: Pekka
authors.initials: P
authors.lastname: Varmanen
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D002417:Cattle; D002939:Ciprofloxacin / Q000494:pharmacology*; D004259:DNA-Directed DNA Polymerase / Q000187:drug effects; D004352:Drug Resistance, Microbial / Q000235:genetics*; D008414:Mastitis, Bovine / Q000188:drug therapy / Q000382:microbiology; D016296:Mutagenesis / Q000187:drug effects*; D017354:Point Mutation / Q000187:drug effects; D013291:Streptococcus / Q000187:drug effects / Q000235:genetics
chemical_list: D000890:Anti-Infective Agents; D002939:Ciprofloxacin; D004259:DNA-Directed DNA Polymerase