title: Ciprofloxacin and trimethoprim cause phage induction and virulence modulation in Staphylococcus aureus.
abstract: In Staphylococcus aureus strains of human origin, phages which integrate into the chromosomal gene coding for beta-hemolysin (hlb) are widely distributed. Most of them encode accessory virulence determinants such as staphylokinase (sak) or enterotoxins. Here, we analyzed the effects of ciprofloxacin and trimethoprim on phage induction and expression of phage-encoded virulence factors by using isolates from patients with cystic fibrosis for which the induction of hlb-converting phages was demonstrated in vivo (C. Goerke, S. Matias y Papenberg, S. Dasbach, K. Dietz, R. Ziebach, B. C. Kahl, and C. Wolz, J. Infect. Dis. 189:724-734, 2004) as well as a phi13 lysogen of phage-cured strain 8325-4. Treatment of lysogens with subinhibitory concentrations of either antibiotic resulted in (i) delysogenization of strains resembling the isolates picked up after chronic lung infection and (ii) replication of phages in the bacterial host in a dose-dependent manner. Ciprofloxacin treatment resulted in enhanced recA transcription, indicating involvement of the SOS response in phage mobilization. Induction of phi13 was linked to elevated expression of the phage-encoded virulence gene sak, chiefly due to the activation of latent phage promoters. In summary, we could show the induction of hlb-converting phages and a subsequent virulence modulation of the host bacterium by ciprofloxacin and trimethoprim.
authors.affiliation: Institut für Medizinische Mikrobiologie und Hygiene, Universitätsklinikum Tübingen, Elfriede-Aulhorn-Str. 6, 72076 Tübingen, Germany. christiane.goerke@med.uni-tuebingen.de
authors.forename: Christiane
authors.initials: C
authors.lastname: Goerke
authors.forename: Johanna
authors.initials: J
authors.lastname: Köller
authors.forename: Christiane
authors.initials: C
authors.lastname: Wolz
mesh_terms: D001427:Bacterial Toxins / Q000235:genetics; D002939:Ciprofloxacin / Q000009:adverse effects*; D015964:Gene Expression Regulation, Bacterial; D015967:Gene Expression Regulation, Viral; D006460:Hemolysin Proteins; D008242:Lysogeny; D008826:Microbial Sensitivity Tests; D013014:SOS Response, Genetics / Q000187:drug effects*; D013108:Sphingomyelin Phosphodiesterase; D013203:Staphylococcal Infections / Q000382:microbiology; D013204:Staphylococcus Phages / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity; D014295:Trimethoprim / Q000009:adverse effects*; D014774:Virulence / Q000187:drug effects* / Q000235:genetics
chemical_list: D001427:Bacterial Toxins; D006460:Hemolysin Proteins; D002939:Ciprofloxacin; D014295:Trimethoprim; D013108:Sphingomyelin Phosphodiesterase; C029878:hlb protein, Staphylococcus aureus