Ciprofloxacin and Trimethoprim Cause Phage Induction and Virulence Modulation in <i>Staphylococcus aureus</i>

<jats:title>ABSTRACT</jats:title> <jats:p> In <jats:italic>Staphylococcus aureus</jats:italic> strains of human origin, phages which integrate into the chromosomal gene coding for β-hemolysin ( <jats:italic>hlb</jats:italic> ) are widely distributed. Most of them encode accessory virulence determinants such as staphylokinase ( <jats:italic>sak</jats:italic> ) 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 <jats:italic>hlb</jats:italic> -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 φ13 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 <jats:italic>recA</jats:italic> transcription, indicating involvement of the SOS response in phage mobilization. Induction of φ13 was linked to elevated expression of the phage-encoded virulence gene <jats:italic>sak</jats:italic> , chiefly due to the activation of latent phage promoters. In summary, we could show the induction of <jats:italic>hlb</jats:italic> -converting phages and a subsequent virulence modulation of the host bacterium by ciprofloxacin and trimethoprim. </jats:p>