A Metabolite of Pseudomonas Triggers Prophage-Selective Lysogenic to Lytic Conversion in Staphylococcus aureus

Abstract

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.

The influence of nanomaterials on pyocyanin production by Pseudomonas aeruginosa

“…Its presence can be problematic, especially in the case of P. aeruginosa infections, as it is a source of reactive oxygen species that, while present in excess, may lead to oxidative stress at the infection site (Hall et al 2016). However, due to the distinct properties of pyocyanin, it shows great potential to be applied in many technologies, e.g., microbial fuel cells (Shen et al 2014), OLED screens (Chen and Li 2004), sensors (Yu et al 2017), agriculture (Meena et al 2020a), cancer and mitochondrial disease treatments (Zhao et al 2014;Moayedi et al 2018;Kohatsu et al 2020;Peruzzo et al 2021), environmental protection (Viana et al 2018) and phage conversion (Jancheva and Thomas 2021). However, pyocyanin remains a costly reagent (e.g., €118 for 5 mg on Merck website).…”

Temperate Bacteriophages—The Powerful Indirect Modulators of Eukaryotic Cells and Immune Functions

“…Surprisingly, metabolites of one bacterial species (in this case Pseudomonas) may induce a prophage internalized with the genome of other bacterial strain (switching the cycle from lysogenic to lytic phages associated with Staphylococcus aureus) [5].…”

The gut bacterial natural product colibactin triggers induction of latent viruses in diverse bacteria

“…[55][56][57] At the same time, metabolites of other bacteria, including known virulence factors (pyocyanin) and bacteria-specific signaling molecules (autoinducers), promote prophage induction. 58,59 Our findings on colibactin, as a gut metabolite, adds to this growing understanding of how small molecules can influence phage behaviors, and importantly, demonstrates phage induction by a bacterial natural product in co-culture.…”