beta-lactam antibiotics induce the SOS response and horizontal transfer of virulence factors in Staphylococcus aureus

Abstract

Antibiotics that interfere with DNA replication and cell viability activate the SOS response. In Staphylococcus aureus, the antibiotic-induced SOS response promotes replication and high-frequency horizontal transfer of pathogenicity island-encoded virulence factors. Here we report that beta-lactams induce a bona fide SOS response in S. aureus, characterized by the activation of the RecA and LexA proteins, the two master regulators of the SOS response. Moreover, we show that beta-lactams are capable of triggering staphylococcal prophage induction in S. aureus lysogens. Consequently, and as previously described for SOS induction by commonly used fluoroquinolone antibiotics, beta-lactam-mediated phage induction also resulted in replication and high-frequency transfer of the staphylococcal pathogenicity islands, showing that such antibiotics may have the unintended consequence of promoting the spread of bacterial virulence factors.

FIG. 1.

Ampicillin-mediated induction factor of the lexA gene in S. aureus RN450 or its recA-mutant strain RN981. The induction factor was measured by quantitative reverse transciption-PCR, and in all cases, it is the ratio of the relative lexA mRNA concentration in ampicillin-treated cells to that in untreated cells. The relative lexA mRNA concentration was calculated as described previously (3). Values were calculated 5 h after ampicillin addition. In each case, the mean value from three independent experiments (each in triplicate) is shown. Amp+, addition of ampicillin at 0.2 μg/ml; Amp−, no ampicillin added.