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Collateral sensitivity profiling in drug-resistant Escherichia coli identifies natural products suppressing cephalosporin resistance.

ABSTRACT: The rapid emergence of antimicrobial resistance presents serious health challenges to the management of infectious diseases, a problem that is further exacerbated by slowing rates of antimicrobial drug discovery in recent years. The phenomenon of collateral sensitivity (CS), whereby resistance to one drug is accompanied by increased sensitivity to another, provides new opportunities to address both these challenges. Here, we present a high-throughput screening platform termed Collateral Sensitivity Profiling (CSP) to map the difference in bioactivity of large chemical libraries across 29 drug-resistant strains of E. coli. CSP screening of 80 commercial antimicrobials demonstrated multiple CS interactions. Further screening of a 6195-member natural product library revealed extensive CS relationships in nature. In particular, we report the isolation of known and new analogues of borrelidin A with potent CS activities against cephalosporin-resistant strains. Co-dosing ceftazidime with borrelidin A slows broader cephalosporin resistance with no recognizable resistance to borrelidin A itself.

SUBMITTER: Liu DY

PROVIDER: S-EPMC10082850 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Collateral sensitivity profiling in drug-resistant Escherichia coli identifies natural products suppressing cephalosporin resistance.

Liu Dennis Y DY Phillips Laura L Wilson Darryl M DM Fulton Kelly M KM Twine Susan M SM Wong Alex A Linington Roger G RG

Nature communications 20230408 1

The rapid emergence of antimicrobial resistance presents serious health challenges to the management of infectious diseases, a problem that is further exacerbated by slowing rates of antimicrobial drug discovery in recent years. The phenomenon of collateral sensitivity (CS), whereby resistance to one drug is accompanied by increased sensitivity to another, provides new opportunities to address both these challenges. Here, we present a high-throughput screening platform termed Collateral Sensitiv ...[more]

PMID: 37031190

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Project description:Escherichia coli strains resistant to extended-spectrum cephalosporins (ESC) are widely distributed in Norwegian broiler production, and the majority harbor transferable IncK or IncI1 plasmids carrying blaCMY-2 Persistent occurrence in broiler farms may occur through the survival of ESC-resistant E. coli strains in the farm environment, or by transfer and maintenance of resistance plasmids within a population of environmental bacteria with high survival abilities. The aim of this study was to determine the transferability of two successful blaCMY-2-carrying plasmids belonging to the incompatibility groups IncK and IncI1 into E. coli and Serratia species recipients. Initially, conjugative plasmid transfer from two E. coli donors to potential recipients was tested in an agar assay. Conjugation was further investigated for selected mating pairs in surface and planktonic assays at temperatures from 12°C to 37°C. Transfer of plasmids was observed on agar, in broth, and in biofilm at temperatures down to 25°C. The IncK plasmid was able to transfer into Serratia marcescens, and transconjugants were able to act as secondary plasmid donors to different E. coli and Serratia species recipients. All transconjugants displayed an AmpC phenotype corresponding to the acquisition of blaCMY-2 In summary, the results indicate that the IncK plasmid may transfer between E. coli and Serratia spp. under conditions relevant for broiler production.IMPORTANCE Certain blaCMY-2-carrying plasmids are successful and disseminated in European broiler production. Traditionally, plasmid transferability has been studied under conditions that are optimal for bacterial growth. Plasmid transfer has previously been reported between E. coli bacteria in biofilms at 37°C and in broth at temperatures ranging from 8 to 37°C. However, intergenus transfer of blaCMY-2-carrying plasmids from E. coli to environmental bacteria in the food-processing chain has not been previously studied. We demonstrate that blaCMY-2-carrying plasmids are capable of conjugative transfer between different poultry-associated bacterial genera under conditions relevant for broiler production. Transfer to Serratia spp. and to hosts with good biofilm-forming abilities and with the potential to act as secondary plasmid donors to new hosts might contribute to the persistence of these resistance plasmids. These results contribute to increased knowledge of factors affecting the persistence of ESC resistance in broiler production and can provide a basis for improvement of routines and preventive measures.

Dataset Information

Collateral sensitivity profiling in drug-resistant Escherichia coli identifies natural products suppressing cephalosporin resistance.

Publications

Collateral sensitivity profiling in drug-resistant Escherichia coli identifies natural products suppressing cephalosporin resistance.

Similar Datasets

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