Natural and synthetic inhibitors of a phage-encoded quorum-sensing receptor affect phage-host dynamics in mixed bacterial communities

Viruses that infect bacteria, called phages, shape the composition of bacterial communities and are important drivers of bacterial evolution. We recently showed that temperate phages, when residing in bacteria (i.e., prophages), are capable of manipulating the bacterial cell-to-cell communication process called quorum sensing (QS). QS relies on the production, release, and population-wide detection of signaling molecules called autoinducers (AI). Gram-negative bacteria commonly employ N-acyl homoserine lactones (HSL) as AIs that are detected by LuxR-type QS receptors. Phage ARM81ld is a prophage of the aquatic bacterium Aeromonas sp. ARM81, and it encodes a homolog of a bacterial LuxR, called LuxR(ARM81ld). LuxR(ARM81ld) detects host Aeromonas-produced C4-HSL, and in response, activates the phage lytic program, triggering death of its host and release of viral particles. Here, we show that phage LuxR(ARM81ld) activity is modulated by noncognate HSL ligands and by a synthetic small molecule inhibitor. We determine that HSLs with acyl chain lengths equal to or longer than C8 antagonize LuxR(ARM81ld). For example, the C8-HSL AI produced by Vibrio fischeri that coexists with Aeromonads in aquatic environments, binds to and inhibits LuxR(ARM81ld), and consequently, protects the host from lysis. Coculture of V. fischeri with the Aeromonas sp. ARM81 lysogen suppresses phage ARM81ld virion production. We propose that the cell density and species composition of the bacterial community could determine outcomes in bacterial-phage partnerships.

Automated summary

This study reveals that bacteriophages can manipulate the bacterial cell-to-cell communication process and trigger the death of host bacteria. The activity of a specific phage receptor is modulated by noncognate signaling molecules and synthetic inhibitors. The findings suggest that the density and species composition of bacterial communities can influence the outcome of bacterial-phage interactions.