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

Research output: Contribution to journalArticle

Authors

  • Alessandro Lazdins
  • Anand Prakash Maurya
  • Claire E. Miller
  • Muhammad Kamruzzaman
  • Shuting Liu
  • Elton Stephens
  • Mona Haratianfar
  • Melissa Chamberlain
  • Jonathan Iredell

Colleges, School and Institutes

External organisations

  • University of Sydney

Abstract

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.

Details

Original languageEnglish
Article numbere0225202
JournalPLoSONE
Volume15
Issue number1
Publication statusPublished - 15 Jan 2020