The arbitrium system has transformed our understanding of phage biology by demonstrating that temperate phages communicate through extracellular peptides to coordinate lysis-lysogeny decisions. Initially considered a highly specific signaling pathway restricted to individual phage lineages, arbitrium communication has now been shown to extend beyond lineage boundaries in some phage systems. Recent studies have shown that non-cognate arbitrium peptides can interact with heterologous receptors, providing evidence of inter-phage crosstalk. Here, we synthesize current knowledge of the molecular basis of arbitrium signaling, the structural determinants of peptide-receptor specificity, and the potential ecological and evolutionary consequences of inter-phage communication. We suggest that arbitrium crosstalk may shape phage ecology by mediating competitive and potentially cooperative interactions within shared signaling environments. We also discuss its potential uses in engineered phage systems, synthetic biology, and microbiome engineering. Collectively, the available evidence broadens the concept of viral communication beyond lineage-specific signaling, while the ecological significance and practical applications of arbitrium crosstalk remain to be established.
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Lomelí‐Ortega et al. (2026) studied this question.
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