Phage-Antibiotic Synergy (PAS): β-Lactam and Quinolone Antibiotics Stimulate Virulent Phage Growth

Although the multiplication of bacteriophages (phages) has a substantial impact on the biosphere, comparatively little is known about how the external environment affects phage production. Here we report that sub-lethal concentrations of certain antibiotics can substantially stimulate the host bacterial cell's production of some virulent phage. For example, a low dosage of cefotaxime, a cephalosporin, increased an uropathogenic Escherichia coli strain's production of the phage ΦMFP by more than 7-fold. We name this phenomenon Phage-Antibiotic Synergy (PAS). A related effect was observed in diverse host-phage systems, including the T4-like phages, with β-lactam and quinolone antibiotics, as well as mitomycin C. A common characteristic of these antibiotics is that they inhibit bacterial cell division and trigger the SOS system. We therefore examined the PAS effect within the context of the bacterial SOS and filamentation responses. We found that the PAS effect appears SOS-independent and is primarily a consequence of cellular filamentation; it is mimicked by cells that constitutively filament. The fact that completely unrelated phages manifest this phenomenon suggests that it confers an important and general advantage to the phages

À l’espagnole ou à la française : résistances et emprunts dans la mode de cour

La confrontation des modes espagnole et française au temps de Louis XIV et de Charles II tient de la gageure. En effet, en dépit d’échanges commerciaux de produits liés à la consommation vestimentaire et d’objets de luxe plus particulièrement destinés au monde de la cour, il est difficile d’en appréhender la réception effective dans ces deux pays ennemis et néanmoins rapprochés par leurs alliances matrimoniales. Tout d’abord se pose le problème des sources. Nous disposons d’un certain nombre ..

The PAS effect of phage T4 on various <i>E. coli</i> SOS and filamentation mutant strains.

<p>T4 was grown on <i>E. coli sulA</i>-inactivated and <i>lexA</i> non-inducible mutant strains (defective SOS systems), as well as an <i>ftsZ</i>-inactivated mutant strain (non-antibiotic induced filamentation), in the presence of disks of cefotaxime (CTX). Isogenic wild-type strains (wt) are also included and representative plaques demonstrating the PAS effect are indicated by red arrows. All plates were photographed at identical magnifications.</p

Plaque sizes of various coliphages with and without cefotaxime (CTX) in Luria agar plates.

<p>Phages RB32 and RB33 were grown on <i>E. coli</i> strain MFP (50 ng/mL CTX) at 37°C; and T4, T3 and T7 were grown on <i>E. coli</i> strain AS19 (30 ng/mL CTX) at 25°C. All plaques were photographed at identical magnifications.</p

The PAS effect of phage ΦMFP on <i>E. coli</i> MFP on Luria-Bertani agar plates.

<p>Only disks containing the β-lactam antibiotics aztreonam and cefixime (indicated by “+” symbols) produced large phage plaques in their proximity. Gentamicin and tetracycline gave no PAS effect. This host strain was resistant to both amoxicillin and trimethoprim/sulfamethoxazole. Note the absence of phages on the left-hand control plate indicating the lack of prophage induction.</p

Plaque sizes of phage ΦMFP on <i>E. coli</i> MFP with and without 50 ng/mL of cefotaxime (CTX) in Luria agar plates.

<p>Plaque sizes of phage ΦMFP on <i>E. coli</i> MFP with and without 50 ng/mL of cefotaxime (CTX) in Luria agar plates.</p