Potentiation of curing by a broad-host-range self-transmissible vector for displacing resistance plasmids to tackle AMR

Autoři: Alessandro Lazdins aff001;  Anand Prakash Maurya aff001;  Claire E. Miller aff001;  Muhammad Kamruzzaman aff003;  Shuting Liu aff001;  Elton R. Stephens aff001;  Georgina S. Lloyd aff001;  Mona Haratianfar aff001;  Melissa Chamberlain aff001;  Anthony S. Haines aff001;  Jan-Ulrich Kreft aff001;  Mark. A. Webber aff002;  Jonathan Iredell aff003;  Christopher M. Thomas aff001
Působiště autorů: Institute of Microbiology & Infection and School of Biosciences, University of Birmingham, Edgbaston, Birmingham, England, United Kingdom aff001;  Institute of Microbiology and Infection, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham, England, United Kingdom aff002;  University of Sydney, Centre for Infectious Disease & Microbiology, Westmead Institute of Medical Research, Westmead, New South Wales, Australia aff003
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: 10.1371/journal.pone.0225202


Plasmids are potent vehicles for spread of antibiotic resistance genes in bacterial populations and often persist in the absence of selection due to efficient maintenance mechanisms. We previously constructed non-conjugative high copy number plasmid vectors that efficiently displace stable plasmids from enteric bacteria in a laboratory context by blocking their replication and neutralising their addiction systems. Here we assess a low copy number broad-host-range self-transmissible IncP-1 plasmid as a vector for such curing cassettes to displace IncF and IncK plasmids. The wild type plasmid carrying the curing cassette displaces target plasmids poorly but derivatives with deletions near the IncP-1 replication origin that elevate copy number about two-fold are efficient. Verification of this in mini IncP-1 plasmids showed that elevated copy number was not sufficient and that the parB gene, korB, that is central to its partitioning and gene control system, also needs to be included. The resulting vector can displace target plasmids from a laboratory population without selection and demonstrated activity in a mouse model although spread is less efficient and requires additional selection pressure.

Klíčová slova:

Antibiotic resistance – Antibiotics – DNA-binding proteins – Plasmid construction – Plasmids – Polymerase chain reaction – Sucrose – Tetracyclines


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