title: The temperate Burkholderia phage AP3 of the Peduovirinae shows efficient antimicrobial activity against B. cenocepacia of the IIIA lineage.
abstract: Burkholderia phage AP3 (vB_BceM_AP3) is a temperate virus of the Myoviridae and the Peduovirinae subfamily (P2likevirus genus). This phage specifically infects multidrug-resistant clinical Burkholderia cenocepacia lineage IIIA strains commonly isolated from cystic fibrosis patients. AP3 exhibits high pairwise nucleotide identity (61.7 %) to Burkholderia phage KS5, specific to the same B. cenocepacia host, and has 46.7-49.5 % identity to phages infecting other species of Burkholderia. The lysis cassette of these related phages has a similar organization (putative antiholin, putative holin, endolysin, and spanins) and shows 29-98 % homology between specific lysis genes, in contrast to Enterobacteria phage P2, the hallmark phage of this genus. The AP3 and KS5 lysis genes have conserved locations and high amino acid sequence similarity. The AP3 bacteriophage particles remain infective up to 5 h at pH 4-10 and are stable at 60 °C for 30 min, but are sensitive to chloroform, with no remaining infective particles after 24 h of treatment. AP3 lysogeny can occur by stable genomic integration and by pseudo-lysogeny. The lysogenic bacterial mutants did not exhibit any significant changes in virulence compared to wild-type host strain when tested in the Galleria mellonella moth wax model. Moreover, AP3 treatment of larvae infected with B. cenocepacia revealed a significant increase (P < 0.0001) in larvae survival in comparison to AP3-untreated infected larvae. AP3 showed robust lytic activity, as evidenced by its broad host range, the absence of increased virulence in lysogenic isolates, the lack of bacterial gene disruption conditioned by bacterial tRNA downstream integration site, and the absence of detected toxin sequences. These data suggest that the AP3 phage is a promising potent agent against bacteria belonging to the most common B. cenocepacia IIIA lineage strains.
authors: Institute of Genetics and Microbiology, University of Wroclaw, Przybyszewskiego 63/77, 51-148, Wroclaw, Poland.
authors: Bartosz
authors: B
authors: Roszniowski
authors: Institute of Genetics and Microbiology, University of Wroclaw, Przybyszewskiego 63/77, 51-148, Wroclaw, Poland.
authors: Agnieszka
authors: A
authors: Latka
authors: Institute of Genetics and Microbiology, University of Wroclaw, Przybyszewskiego 63/77, 51-148, Wroclaw, Poland.
authors: Barbara
authors: B
authors: Maciejewska
authors: Laboratory of Gene Technology, KU Leuven, Kasteelpark Arenberg 21, box 2462, 3001, Leuven, Belgium.
authors: Dieter
authors: D
authors: Vandenheuvel
authors: Institute of Genetics and Microbiology, University of Wroclaw, Przybyszewskiego 63/77, 51-148, Wroclaw, Poland.
authors: Tomasz
authors: T
authors: Olszak
authors: Laboratory of Gene Technology, KU Leuven, Kasteelpark Arenberg 21, box 2462, 3001, Leuven, Belgium.|Department of Applied Biosciences, Ghent University, Valentin Vaerwyckweg 1, 9000, Ghent, Belgium.
authors: Yves
authors: Y
authors: Briers
authors: Applied Sciences, University of Northumbria, Ellison Building EBD222, Newcastle upon Tyne, NE1 8ST, UK.
authors: Giles S
authors: GS
authors: Holt
authors: Center for Experimental Medicine, Queen's University of Belfast, 97 Lisburn Rd., Belfast, BT9 7BL, UK.
authors: Miguel A
authors: MA
authors: Valvano
authors: Laboratory of Gene Technology, KU Leuven, Kasteelpark Arenberg 21, box 2462, 3001, Leuven, Belgium.
authors: Rob
authors: R
authors: Lavigne
authors: Applied Sciences, University of Northumbria, Ellison Building EBD222, Newcastle upon Tyne, NE1 8ST, UK.
authors: Darren L
authors: DL
authors: Smith
authors: Institute of Genetics and Microbiology, University of Wroclaw, Przybyszewskiego 63/77, 51-148, Wroclaw, Poland. zuzanna.drulis-kawa@uwr.edu.pl.
authors: Zuzanna
authors: Z
authors: Drulis-Kawa
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000302:isolation & purification*; D001435:Bacteriophages / Q000235:genetics* / Q000302:isolation & purification* / Q000502:physiology*; D019117:Burkholderia / Q000821:virology*; D019121:Burkholderia Infections / Q000382:microbiology; D057508:Burkholderia cenocepacia / Q000821:virology; D042602:Burkholderia cepacia complex / Q000821:virology*; D003550:Cystic Fibrosis / Q000382:microbiology; D016679:Genome, Viral; D058507:Host Specificity; D006801:Humans; D008242:Lysogeny; D009036:Moths / Q000821:virology; D017422:Sequence Analysis, DNA; D014774:Virulence
chemical_list: D000890:Anti-Infective Agents
keywords: Burkholderia cepacia lineage IIIA; Peduovirinae; Temperate phage