Antibiotic-mediated prophage activation: Mechanisms, consequences, and therapeutic implications

Prophages, as an integral part of bacterial genomes, play a pivotal role in regulating host virulence and shaping bacterial evolution. Exposure to antibiotics, particularly those that cause DNA damage, can trigger a shift from lysogeny to the lytic cycle, i.e., initiate prophage induction.

This review compares the effects of various antibiotic classes on prophage induction, with particular emphasis on the associated clinical consequences.

This process can lead to undesirable consequences, such as increased toxin production, enhanced transduction frequency, and modulation of host phenotypes and virulence traits. Among the most potent inducers are fluoroquinolones, such as ciprofloxacin, which activate stx-harbouring prophages in enterohemorrhagic Escherichia coli (EHEC), resulting in elevated Shiga toxin production and disease exacerbation. This effect is primarily mediated through activation of the bacterial SOS response, although other mechanisms may also contribute. Similarly, subinhibitory concentrations of certain β-lactams, sulphonamides, nitrofurans, and fosfomycin can induce prophages, although the extent of induction varies depending on the antibiotic concentration, phage type, bacterial strain, and detection methodology. The antibiotics that predominantly suppress or inhibit phage induction are aminoglycosides, some macrolides, and newer generation tetracyclines.

Further studies on antibiotic-mediated phage induction, particularly those focusing on elucidating the underlying mechanisms of this phenomenon, are necessary to maximize its beneficial effects and minimize potential adverse outcomes during therapy.