posted on 2021-05-12, 14:33authored byMagdalena Jancheva, Thomas Böttcher
Bacteriophages have
major impact on their microbial hosts and shape
entire microbial communities. The majority of these phages are latent
and reside as prophages integrated in the genomes of their microbial
hosts. A variety of intricate regulatory systems determine the switch
from a lysogenic to lytic life style, but so far strategies are lacking
to selectively control prophage induction by small molecules. Here
we show that Pseudomonas aeruginosa deploys a trigger
factor to hijack the lysogenic to lytic switch of a polylysogenic Staphylococcus aureus strain causing the selective production
of only one of its prophages. Fractionating extracts of P. aeruginosa identified the phenazine pyocyanin
as a highly potent prophage inducer of S. aureus that, in contrast to mitomycin C, displayed prophage
selectivity. Mutagenesis and biochemical investigations confirm the
existence of a noncanonical mechanism beyond SOS-response that is
controlled by the intracellular oxidation level and is prophage-selective.
Our results demonstrate that human pathogens can produce metabolites
triggering lysogenic to lytic conversion in a prophage-selective manner.
We anticipate our discovery to be the starting point of unveiling
metabolite-mediated microbe–prophage interactions and laying
the foundations for a selective small molecule controlled manipulation
of prophage activity. These could be for example applied to control
microbial communities by their built-in destruction mechanism in a
novel form of phage therapy or for the construction of small molecule-inducible
switches in synthetic biology.