Antibiotic-induced morphological changes boost viral predation on bacterial hosts
Therapeutic phages used alongside antibiotics show potential for combating antibiotic-resistant bacteria. Some antibiotics induce physiological changes in bacteria, such as filamentation, which enhances phage infection and replication, a phenomenom known as Phage-Antibiotic Synergy (PAS).
Sublethal doses of ciprofloxacin and cephalexin applied to E. coli before phage infection, trigger DNA repair and stress tolerance pathways, leading to filamentation and reduced bacterial division. These filamentous bacteria exhibit increased mutagenesis, making them prime targets for phages due to their enlarged surface area that increased adsorption. In addition, our mathematical model confirms that filamentation amplifies phage replication on mutagenic cells, ultimately limiting mutagenesis.
In addition, we investigated how antibiotics affect phage predation during plaque formation in semi-solid media, a condition without agitation where phage and cells mixing is impaired. Antibiotic-induced morphological changes in bacteria impact host growth and diffusion of phages, leading to larger plaques. Interestingly, not only cell elongation, but also cell rounding favor phage predation, although with different characteristics. Our model integrates these factors, showing that altered host morphology enhances phage spread and bacterial eradication.
This work provides a better understanding of the current use of therapeutic phages in combination with antibiotics to improve therapeutic outcomes. It offers new avenues for optimizing phage therapy by taking advantage of bacterial physiology and host-pathogen dynamics.
Short bio
Mireille Ansaldi is CNRS research director at the Laboratoire de Chimie Bactérienne (CNRS-Aix Marseille Université) where she leads a research team focusing on different aspects of bacteriophage biology combining diverse and complementary skills ranging from molecular and cellular microbiology to genomics, bioinformatics, modeling and artificial intelligence. Her group is a founding member of the Phages.fr bacteriophage research network.
Laboratory of the speaker
Laboratoire de Chimie Bactérienne, Marseille
Invited by
Manish KUSHWAHA
