Viral satellites exploit phage proteins to escape degradation of the bacterial host chromosome

Abstract

SummaryPhage defense systems are often found on mobile genetic elements (MGEs), where they constitutively defend against invaders or are induced to respond to new assaults. Some MGEs, the phage satellites, exploit phages for their own transmission after induction, reducing phage production and protecting their hosts in the process. One such satellite in Vibrio cholerae, PLE, is triggered by the lytic phage ICP1 to excise from the chromosome, replicate, and transduce to neighboring cells, completely sabotaging phage production. Here, we found that ICP1 has evolved to possess one of two syntenic loci encoding an SF1B-type helicase, either of which PLE can exploit to directly drive PLE replication. Further, loss of PLE mobilization limits anti-phage activity due to phage-mediated degradation of the bacterial genome. Our work provides insight into the unique challenges imposed on the parasites of lytic phages and underscores the adaptions of these satellites to their ever-evolving target phage.

DominantVibrio choleraephage exhibits lysis inhibition sensitive to disruption by a defensive phage satellite

“…PRALINE was used to create amino acid alignments of LidI (79). Homologs of TeaA (30% identity over 85% of the query) and ArrA (20% identity over 75% of the query) were identified with BLASTP (80) and arranged into phylogenetic trees as previously described (22). Briefly, alignments were completed with MUSCLE v3.8.31 (81) and a bootstrapped (n=100) maximum-likelihood phylogenic tree was solved with PhyML 3.0 (82).…”

“…The predominant phage in cholera patient samples is ICP1, a lytic myovirus (19). This phage and its host have been locked in a dynamic arms race with no clear winner as both V. cholerae and ICP1 continue to be isolated from patients in the cholera endemic region of Bangladesh (19)(20)(21)(22). Added into the evolutionary fray is a phage satellite called the PLE (phage-inducible chromosomal island-like element), which is found in the chromosome of V. cholerae clinical isolates (23,24).…”

“…Each PLE provides V. cholerae with a clear fitness benefit in the fight against ICP1 by completely blocking the production of ICP1 progeny phage (23). PLE hijacks an ICP1-encoded protein to excise from the bacterial chromosome following infection (25), where it replicates to high copy using both PLE and ICP1-encoded proteins (22,26). PLE is then hypothesized to steal ICP1 structural components to transduce the PLE genome to naïve recipient cells (23).…”

“…In the face of this assault, ICP1 has acquired a functional Type I-F CRISPR-Cas adaptive immune system to target PLE in a sequence-specific manner, restoring ICP1 progeny phage production and overcoming PLE (24,27). While the full extent of ICP1, PLE, and V. cholerae interactions are unknown and continuing to evolve, efforts to understand how the PLE completely restricts ICP1 production have yet to identify any single PLE-encoded gene product that is necessary for inhibition, suggesting that multiple inhibitory strategies act synergistically to fully eliminate phage production (22,23,26). From the only characterized processes, namely PLE excision and replication, it is clear that PLE requires phage-encoded products, consequently depending on ICP1 for horizontal transmission, but, uncharacteristic of other phage satellites like the well characterized Staphylococcus aureus pathogenicity islands (SAPIs) which only decrease the number of progeny virions produced, PLE completely abolishes ICP1 production -a balancing act that likely requires the exploitation of select products at just the right time during the 20 minutes before PLE-mediated accelerated lysis.…”

“…gene product that is necessary for inhibition, suggesting that multiple inhibitory strategies act synergistically to fully eliminate phage production (22,23,26). From the only characterized processes, namely PLE excision and replication, it is clear that PLE requires phage-encoded products, consequently depending on ICP1 for horizontal transmission, but, uncharacteristic of other phage satellites like the well characterized Staphylococcus aureus pathogenicity islands (SAPIs) which only decrease the number of progeny virions produced, PLE completely abolishes ICP1 production -a balancing act that likely requires the exploitation of select products at just the right time during the 20 minutes before PLE-mediated accelerated lysis.…”