Bacterial threat assessment of bacteriophage infection is mediated by intracellular polyamine accumulation and Gac/Rsm signaling

Abstract

When eukaryotic cells are killed by pathogenic microorganisms, damage-associated and pathogen-associated signals are generated that alert other cells of nearby danger. Bacteria can detect the death of their kin; however, how bacteria make threat assessments of cellular injury is largely unexplored. Here we show that polyamines released by lysed bacteria serve as damage-associated molecules in Pseudomonas aeruginosa. In response to exogenous polyamines, Gac/Rsm and cyclic-di-GMP signaling is activated and intracellular polyamine levels increase. In the absence of a threat, polyamines are catabolized, and intracellular polyamines return to basal levels, but cells infected by bacteriophage increase and maintain intracellular polyamine levels, which inhibits phage replication. Phage species not inhibited by polyamines did not trigger polyamine accumulation by P. aeruginosa, suggesting polyamine accumulation and metabolism are targets in the phage-host arms-race. Our results suggest that like eukaryotic cells, bacteria can differentiate damage-associated and pathogen-associated signals to make threat assessments of cellular injury.

Phage T3 overcomes the BREX defence through SAM cleavage and inhibition of SAM synthesis

“…61 Recent work demonstrated that polyamines inhibit phage replication and once released from lysed infected cells serve as signalling molecules to activate phage defence in neighbouring uninfected cells through the Gac/Rsm pathway. 62 Again, it might be expected that phage-encoded SAMases would reduce the synthesis of polyamines and thus either protect the phage from direct inhibition or prevent the activation of host defences.…”

Fight not flight: parasites drive the bacterial evolution of resistance, not escape

“…Bacteria have abundant strategies to resist phage infection (Hampton et al 2020), including the capability to activate defenses when they detect infections in nearby neighbors (de Mattos et al 2022), as well as complex abilities to sense and physically navigate their environment (Keegstra et al 2022; Wadhwa and Berg 2022). Indeed, both eukaryotes and bacteria have been found to avoid parasite exposure (Bru et al 2019; Gibson and Amoroso 2022).…”

“…Bacteria can also carry any number of cytoplasmic defenses that operate after a phage infects the cell. In fact, bacteria can even activate intracellular defenses in response to signals from phage-infected neighbors (Høyland-Kroghsbo et al 2013, 2017; Tan et al 2015; Patterson et al 2016; Baskerville et al 2018; de Mattos et al 2022). Moreover, recent advancements have revealed an enormous diversity of previously-undiscovered defense systems (Millman et al 2020, 2022), suggesting that many more bacterial responses to phages remain to be found.…”