Peptide wrwycr inhibits the excision of several prophages and traps holliday junctions inside bacteria.
Peptide inhibitors of phage lambda site-specific recombination were previously isolated by screening synthetic combinatorial peptide libraries. These inhibitors cause the accumulation of complexes between the recombinase and the Holliday junction intermediate of several highly divergent tyrosine recombinases. Peptide WRWYCR and its d-amino acid derivative bind to the center of protein-free junctions and prevent their resolution either by site-specific recombinases or by junction resolvases or helicases. With lesser affinity, the peptides also bind to branched DNA molecules that mimic replication forks. The peptides are bactericidal to both gram-positive and gram-negative bacteria, presumably because they can interfere with DNA repair and with chromosome dimer resolution by the XerC and XerD tyrosine recombinases. In order to test the correspondence between their mechanism in vivo and in vitro, we have tested and shown peptide wrwycr's ability to inhibit the excision of several prophages (lambda, P22, Gifsy-1, Gifsy-2, Fels-1, Fels-2) and to trap Holliday junction intermediates of phage lambda site-specific recombination in vivo. In addition, we found that the peptide inhibits replication of the Salmonella prophage Fels-1 while integrated in the chromosome. These findings further support the proposed mechanistic basis for the antimicrobial activity of the peptide and its use as a tool to dissect strand exchange-dependent DNA repair within cells.
Gunderson
Carl W
CW
Department of Biology and Center for Microbial Sciences, San Diego State University, California 92182-4614, USA.
Boldt
Jeffrey L
JL
Authement
R Nathan
RN
Segall
Anca M
AM
D001287:Attachment Sites, Microbiological; D001419:Bacteria / Q000235:genetics / Q000821:virology*; D045566:DNA, Cruciform / Q000235:genetics*; D004279:DNA, Viral / Q000235:genetics*; D010455:Peptides / Q000494:pharmacology*; D039002:Prophages / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D011995:Recombination, Genetic / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
D045566:DNA, Cruciform; D004279:DNA, Viral; D010455:Peptides