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Viral evasion of a bacterial suicide system by RNA-based molecular mimicry enables infectious altruism.

Blower TR, Evans TJ, Przybilski R, Fineran PC, Salmond GP - PLoS Genet. (2012)

Bottom Line: The ΦTE escape mutants had expanded the number of these "pseudo-ToxI" genetic repeats and, in one case, an escape phage had "hijacked" ToxI from the plasmid-borne toxIN locus, through recombination.This is the first example of a non-coding RNA encoded by a phage that evolves by selective expansion and recombination to enable viral suppression of a defensive bacterial suicide system.Furthermore, the ΦTE escape phages had evolved enhanced capacity to transduce replicons expressing ToxIN, demonstrating virus-mediated horizontal transfer of genetic altruism.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.

ABSTRACT
Abortive infection, during which an infected bacterial cell commits altruistic suicide to destroy the replicating bacteriophage and protect the clonal population, can be mediated by toxin-antitoxin systems such as the Type III protein-RNA toxin-antitoxin system, ToxIN. A flagellum-dependent bacteriophage of the Myoviridae, ΦTE, evolved rare mutants that "escaped" ToxIN-mediated abortive infection within Pectobacterium atrosepticum. Wild-type ΦTE encoded a short sequence similar to the repetitive nucleotide sequence of the RNA antitoxin, ToxI, from ToxIN. The ΦTE escape mutants had expanded the number of these "pseudo-ToxI" genetic repeats and, in one case, an escape phage had "hijacked" ToxI from the plasmid-borne toxIN locus, through recombination. Expression of the pseudo-ToxI repeats during ΦTE infection allowed the phage to replicate, unaffected by ToxIN, through RNA-based molecular mimicry. This is the first example of a non-coding RNA encoded by a phage that evolves by selective expansion and recombination to enable viral suppression of a defensive bacterial suicide system. Furthermore, the ΦTE escape phages had evolved enhanced capacity to transduce replicons expressing ToxIN, demonstrating virus-mediated horizontal transfer of genetic altruism.

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DNA alignment of ΦTE-phage escape loci and comparison with ToxI.Long grey boxes enclose invariant sequences bordering the pseudo-ToxI repeats. Grey shaded bases indicate the start of a DNA repeat. Single, boxed, bases mark the start of a ToxI antitoxic RNA and the predicted equivalent pseudo-ToxI RNAs in the ΦTE phages. Prime symbols denote single base-pair differences between sequences. Asterisks indicate the single base addition at the end of each pseudo-ToxI RNA repeat. A circumflex, ∧, indicates the single variable base in ToxI, where the first repeat shows a T in this position rather than a C for all other repeats. The numbering system identifies the 36 nucleotides within an antitoxic ToxI pseudoknot, numbered according to position relative to the DNA repeat, thereby beginning at base −3, −2, −1, 0 and through to base 32 [13]. Underlined bases denote the variable 2T or 3T sequences.
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pgen-1003023-g002: DNA alignment of ΦTE-phage escape loci and comparison with ToxI.Long grey boxes enclose invariant sequences bordering the pseudo-ToxI repeats. Grey shaded bases indicate the start of a DNA repeat. Single, boxed, bases mark the start of a ToxI antitoxic RNA and the predicted equivalent pseudo-ToxI RNAs in the ΦTE phages. Prime symbols denote single base-pair differences between sequences. Asterisks indicate the single base addition at the end of each pseudo-ToxI RNA repeat. A circumflex, ∧, indicates the single variable base in ToxI, where the first repeat shows a T in this position rather than a C for all other repeats. The numbering system identifies the 36 nucleotides within an antitoxic ToxI pseudoknot, numbered according to position relative to the DNA repeat, thereby beginning at base −3, −2, −1, 0 and through to base 32 [13]. Underlined bases denote the variable 2T or 3T sequences.

Mentions: Escape phage ΦTE-A had a final genome size of 142,457 bp, whilst ΦTE-C and ΦTE-E were siblings with an identical genome of 142,497 bp. By comparing the finished sequences of ΦTE and the escape phages, a single difference was identified; the escape genomes had expanded in size within the intergenic locus between phiTE_202 and phiTE_203. This ‘escape locus’ between 106,714–106,772 bp of ΦTE wt (Figure 1C), contained a nucleotide sequence closely resembling that of the ToxI antitoxin from ToxIN (Figure 2). Within the escape phages, the number of DNA repeats had been expanded from 1.5 repeats to 4.5 (ΦTE-A) or 5.5 (ΦTE-C and -E; Figure 3, Table S3). The remaining escape phages were analysed by specifically sequencing amplicons generated from these escape loci. In phages ΦTE-B and ΦTE-D, the locus had also expanded to 5.5 repeats. The nature of each repeat varied in one position, in that a trinucleotide ‘TTT’ (denoted 3T) sometimes appeared in a repeat as a dinucleotide ‘TT’ (denoted 2T) (Figure 2 and Table S3). This difference separated ΦTE-B and -D from ΦTE-C and -E.


Viral evasion of a bacterial suicide system by RNA-based molecular mimicry enables infectious altruism.

Blower TR, Evans TJ, Przybilski R, Fineran PC, Salmond GP - PLoS Genet. (2012)

DNA alignment of ΦTE-phage escape loci and comparison with ToxI.Long grey boxes enclose invariant sequences bordering the pseudo-ToxI repeats. Grey shaded bases indicate the start of a DNA repeat. Single, boxed, bases mark the start of a ToxI antitoxic RNA and the predicted equivalent pseudo-ToxI RNAs in the ΦTE phages. Prime symbols denote single base-pair differences between sequences. Asterisks indicate the single base addition at the end of each pseudo-ToxI RNA repeat. A circumflex, ∧, indicates the single variable base in ToxI, where the first repeat shows a T in this position rather than a C for all other repeats. The numbering system identifies the 36 nucleotides within an antitoxic ToxI pseudoknot, numbered according to position relative to the DNA repeat, thereby beginning at base −3, −2, −1, 0 and through to base 32 [13]. Underlined bases denote the variable 2T or 3T sequences.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3475682&req=5

pgen-1003023-g002: DNA alignment of ΦTE-phage escape loci and comparison with ToxI.Long grey boxes enclose invariant sequences bordering the pseudo-ToxI repeats. Grey shaded bases indicate the start of a DNA repeat. Single, boxed, bases mark the start of a ToxI antitoxic RNA and the predicted equivalent pseudo-ToxI RNAs in the ΦTE phages. Prime symbols denote single base-pair differences between sequences. Asterisks indicate the single base addition at the end of each pseudo-ToxI RNA repeat. A circumflex, ∧, indicates the single variable base in ToxI, where the first repeat shows a T in this position rather than a C for all other repeats. The numbering system identifies the 36 nucleotides within an antitoxic ToxI pseudoknot, numbered according to position relative to the DNA repeat, thereby beginning at base −3, −2, −1, 0 and through to base 32 [13]. Underlined bases denote the variable 2T or 3T sequences.
Mentions: Escape phage ΦTE-A had a final genome size of 142,457 bp, whilst ΦTE-C and ΦTE-E were siblings with an identical genome of 142,497 bp. By comparing the finished sequences of ΦTE and the escape phages, a single difference was identified; the escape genomes had expanded in size within the intergenic locus between phiTE_202 and phiTE_203. This ‘escape locus’ between 106,714–106,772 bp of ΦTE wt (Figure 1C), contained a nucleotide sequence closely resembling that of the ToxI antitoxin from ToxIN (Figure 2). Within the escape phages, the number of DNA repeats had been expanded from 1.5 repeats to 4.5 (ΦTE-A) or 5.5 (ΦTE-C and -E; Figure 3, Table S3). The remaining escape phages were analysed by specifically sequencing amplicons generated from these escape loci. In phages ΦTE-B and ΦTE-D, the locus had also expanded to 5.5 repeats. The nature of each repeat varied in one position, in that a trinucleotide ‘TTT’ (denoted 3T) sometimes appeared in a repeat as a dinucleotide ‘TT’ (denoted 2T) (Figure 2 and Table S3). This difference separated ΦTE-B and -D from ΦTE-C and -E.

Bottom Line: The ΦTE escape mutants had expanded the number of these "pseudo-ToxI" genetic repeats and, in one case, an escape phage had "hijacked" ToxI from the plasmid-borne toxIN locus, through recombination.This is the first example of a non-coding RNA encoded by a phage that evolves by selective expansion and recombination to enable viral suppression of a defensive bacterial suicide system.Furthermore, the ΦTE escape phages had evolved enhanced capacity to transduce replicons expressing ToxIN, demonstrating virus-mediated horizontal transfer of genetic altruism.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.

ABSTRACT
Abortive infection, during which an infected bacterial cell commits altruistic suicide to destroy the replicating bacteriophage and protect the clonal population, can be mediated by toxin-antitoxin systems such as the Type III protein-RNA toxin-antitoxin system, ToxIN. A flagellum-dependent bacteriophage of the Myoviridae, ΦTE, evolved rare mutants that "escaped" ToxIN-mediated abortive infection within Pectobacterium atrosepticum. Wild-type ΦTE encoded a short sequence similar to the repetitive nucleotide sequence of the RNA antitoxin, ToxI, from ToxIN. The ΦTE escape mutants had expanded the number of these "pseudo-ToxI" genetic repeats and, in one case, an escape phage had "hijacked" ToxI from the plasmid-borne toxIN locus, through recombination. Expression of the pseudo-ToxI repeats during ΦTE infection allowed the phage to replicate, unaffected by ToxIN, through RNA-based molecular mimicry. This is the first example of a non-coding RNA encoded by a phage that evolves by selective expansion and recombination to enable viral suppression of a defensive bacterial suicide system. Furthermore, the ΦTE escape phages had evolved enhanced capacity to transduce replicons expressing ToxIN, demonstrating virus-mediated horizontal transfer of genetic altruism.

Show MeSH
Related in: MedlinePlus