Ville Ojala1,2, Sari Mattila1,2, Ville Hoikkala1,2, Jaana Kh Bamford1,2, Teppo Hiltunen1,2, Matti Jalasvuori1,2. 1. Department of Biological & Environmental Science, Centre of Excellence in Biological Interactions, University of Jyväskylä, Jyväskylä, Finland. 2. Department of Food & Environmental Sciences/Microbiology & Biotechnology, University of Helsinki, PO Box 65, Helsinki 00014, Finland.
Abstract
AIM: To investigate the potential evolutionary obstacles in the sustainable therapeutic use of plasmid-dependent phages to control the clinically important conjugative plasmid-mediated dissemination of antibiotic resistance genes to pathogenic bacteria. MATERIALS & METHODS: The lytic plasmid-dependent phage PRD1 and the multiresistance conferring plasmid RP4 in an Escherichia coli host were utilized to assess the genetic and phenotypic changes induced by combined phage and antibiotic selection. RESULTS & CONCLUSIONS: Resistance to PRD1 was always coupled with either completely lost or greatly reduced conjugation ability. Reversion to full conjugation efficiency was found to be rare, and it also restored the susceptibility to plasmid-dependent phages. Consequently, plasmid-dependent phages constitute an interesting candidate for development of sustainable anticonjugation/antiresistance therapeutic applications.
AIM: To investigate the potential evolutionary obstacles in the sustainable therapeutic use of plasmid-dependent phages to control the clinically important conjugative plasmid-mediated dissemination of antibiotic resistance genes to pathogenic bacteria. MATERIALS & METHODS: The lytic plasmid-dependent phage PRD1 and the multiresistance conferring plasmid RP4 in an Escherichia coli host were utilized to assess the genetic and phenotypic changes induced by combined phage and antibiotic selection. RESULTS & CONCLUSIONS: Resistance to PRD1 was always coupled with either completely lost or greatly reduced conjugation ability. Reversion to full conjugation efficiency was found to be rare, and it also restored the susceptibility to plasmid-dependent phages. Consequently, plasmid-dependent phages constitute an interesting candidate for development of sustainable anticonjugation/antiresistance therapeutic applications.
Authors: Johannes Cairns; Katariina Koskinen; Reetta Penttinen; Tommi Patinen; Anna Hartikainen; Roosa Jokela; Liisa Ruusulehto; Sirja Viitamäki; Sari Mattila; Teppo Hiltunen; Matti Jalasvuori Journal: mSystems Date: 2018-10-02 Impact factor: 6.496