Viral Satellites Exploit Phage Proteins to Escape Degradation of the Bacterial Host Chromosome

Abstract

Phage defense systems are often found on mobile genetic elements (MGEs), where they constitutively defend against invaders or are induced to respond to new assaults. Phage satellites, one type of MGE, are induced during phage infection to promote their own transmission, reducing phage production and protecting their hosts in the process. One such satellite in Vibrio cholerae, phage-inducible chromosomal island-like element (PLE), sabotages the lytic phage ICP1, which triggers PLE excision from the bacterial chromosome, replication, and transduction to neighboring cells. Analysis of patient stool samples from different geographic regions revealed that ICP1 has evolved to possess one of two syntenic loci encoding an SF1B-type helicase, either of which PLE exploits to drive replication. Further, loss of PLE mobilization limits anti-phage activity because of phage-mediated degradation of the bacterial genome. Our work provides insight into the unique challenges facing parasites of lytic phages and underscores the adaptions of satellites to their ever-evolving target phage.

A family of viral satellites manipulates invading virus gene expression and affects cholera toxin mobilization

“…We suspect that the timing of PLE gene cluster expression has evolved to take advantage of ICP1's own transcriptional program. Coordination between PLE gene expression and ICP1's gene expression would be consistent with PLEs' reliance on ICP1 gene products for key steps of the PLE lifecycle [22][23][24][25].…”

“…Aside from RepA, the replication initiation factor that directly interacts with the PLE origin of replication, PLE does not appear to encode dedicated replication machinery [23]. Further, PLE has been shown to rely on at least some ICP1 gene products for replication [23,24]. PLE also does not encode identifiable structural genes, and requires the same viral receptor as ICP1 for mobilization [14], suggesting that like other phage satellites [57], PLE is packaged within the same virion structural components as its host-phage.…”

“…Successful PLE parasitism does not abrogate cell lysis, but results in the complete restriction of ICP1 and the release of PLE transducing particles [14] (S1 Fig). The tractable genetics of V. cholerae facilitates mechanistic studies of PLE gene products, and insights have been gained regarding chromosomal excision of PLE [22], PLE DNA replication [23,24], and PLE manipulation of lysis kinetics during infection [25]. Notably, ICP1 genome editing is also possible [26], allowing manipulation of both sides of this host-parasite relationship.…”

“…Four of the five known PLEs are integrated into repeats of the superintegron, an array of selfish and mobile elements in the V. cholerae small chromosome [14]. PLEs mobility, along with the extensive and growing library of ICP1 isolates, allows PLEs to be compared in shared strain backgrounds during infection by contemporaneous and non-contemporaneous ICP1 isolates [14,22,24]. These experiments have shown that PLE and ICP1 are engaged in a co-evolutionary arms race, with different pairings of PLEs and ICP1 isolates having different infection outcomes.…”

Gold Standard Cholera Diagnostics Are Tarnished by Lytic Bacteriophage and Antibiotics

“…One explanation is lytic bacteriophage and antibiotics inhibit bacterial growth below the diagnostic limits of detection. Alternatively, bacteriophage nucleases, or host nucleases responding to bacteriophage infection, may differentially digest host chromosomal DNA to the point that PCR fails (42,43).…”