Potentiation of curing by a broad-host-range self-transmissible vector for displacing resistance plasmids to tackle AMR
- Resource Type
- Authors
- Anand Prakash Maurya; Georgina S. Lloyd; Anthony S. Haines; Alessandro Lazdins; Claire E Miller; Jan-Ulrich Kreft; Shuting Liu; Melissa Chamberlain; M. Kamruzzaman; Elton R. Stephens; Jonathan R. Iredell; Mona Haratianfar; Christopher M. Thomas; Mark A. Webber
- Source
- PLoS ONE, Vol 15, Iss 1, p e0225202 (2020)
PLoS ONE
- Subject
- Sucrose
Molecular biology
Artificial Gene Amplification and Extension
Disaccharides
Biochemistry
Polymerase Chain Reaction
Mice
Plasmid
Antibiotics
Mobile Genetic Elements
Medicine and Health Sciences
Vector (molecular biology)
Genetics
0303 health sciences
education.field_of_study
Multidisciplinary
Antimicrobials
Organic Compounds
Escherichia coli Proteins
Drugs
Bacterial Infections
Genomics
Nucleic acids
Chemistry
Tetracyclines
Conjugation, Genetic
Physical Sciences
Medicine
Plasmids
Research Article
DNA Copy Number Variations
Forms of DNA
Science
Population
Carbohydrates
Context (language use)
DNA Primase
Biology
DNA construction
Microbiology
Host Specificity
Bacterial genetics
03 medical and health sciences
Genetic Elements
Microbial Control
Drug Resistance, Bacterial
DNA-binding proteins
Escherichia coli
Animals
Humans
education
Gene
030304 developmental biology
Pharmacology
Biology and life sciences
030306 microbiology
Organic Chemistry
Wild type
Chemical Compounds
Proteins
DNA
Gastrointestinal Microbiome
Research and analysis methods
Disease Models, Animal
Molecular biology techniques
Antibiotic Resistance
Plasmid Construction
Antimicrobial Resistance
Low copy number
- Language
- English
- ISSN
- 1932-6203
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.