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Natural and synthetic inhibitors of a phage-encoded quorum-sensing receptor affect phage-host dynamics in mixed
Justin E Silpe1,2, Olivia P Duddy1, Bonnie L Bassler1,2
1Department of Molecular Biology, Princeton University, Princeton, NJ 08544.
Abstract:
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 LuxRARM81ld. LuxRARM81ld 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 LuxRARM81ld 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 LuxRARM81ld. For example, the C8-HSL AI produced by Vibrio fischeri that coexists with Aeromonads in aquatic environments, binds to and inhibits LuxRARM81ld, 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.
Insights
Bacteriophages can manipulate bacterial communication. Phage LuxRARM81ld is inhibited by longer acyl chain autoinducers, protecting host bacteria from lysis and influencing microbial community dynamics.
Area of Science:
- Microbiology
- Virology
- Molecular Biology
Background:
- Bacteriophages (viruses infecting bacteria) are key drivers of bacterial evolution and community structure.
- Temperate phages, as prophages within bacteria, can manipulate bacterial quorum sensing (QS), a cell-to-cell communication system.
- Gram-negative bacteria use N-acyl homoserine lactones (HSL) as autoinducers (AI) for QS, detected by LuxR-type receptors.
Purpose of the Study:
- To investigate how phage LuxRARM81ld, a QS receptor homolog encoded by phage ARM81ld, is modulated by different HSL ligands.
- To determine the effect of noncognate HSLs and a synthetic inhibitor on LuxRARM81ld activity and phage-induced lysis.
- To explore the ecological implications of HSL-mediated phage-host interactions in aquatic bacterial communities.
Main Methods:
- Characterization of phage LuxRARM81ld activity using various HSL ligands, including those produced by coexisting bacteria.
- Assessment of the impact of HSLs on phage-induced bacterial lysis and virion production.
- Coculture experiments with Aeromonas sp. ARM81 lysogens and Vibrio fischeri to observe community-level effects.
Main Results:
- Phage LuxRARM81ld activity is modulated by noncognate HSL ligands and a synthetic inhibitor.
- HSL molecules with acyl chain lengths of C8 or longer antagonize LuxRARM81ld function.
- Vibrio fischeri-produced C8-HSL inhibits LuxRARM81ld, protecting Aeromonas sp. ARM81 from phage-induced lysis and reducing virion production.
Conclusions:
- Bacterial autoinducers can act as antagonists of phage-encoded QS receptors, influencing phage-host dynamics.
- Interactions between bacterial species and their phages are influenced by the chemical communication landscape.
- Community composition and cell density may dictate the outcomes of bacterial-phage partnerships in aquatic environments.
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