DNA Damage Repair and Drug Efflux as Potential Targets for Reversing Low or Intermediate Ciprofloxacin Resistance in E. coli K-12

Frontiers in Microbiology
Rasmus N KlitgaardAnders Løbner-Olesen

Abstract

Ciprofloxacin is a potent antibacterial drug that is widely used in human clinical applications. As a consequence of its extensive use, resistance has emerged in almost all clinically relevant bacterial species. A mean to combat the observed ciprofloxacin resistance is by reversing it via co-administration of a potentiating compound, also known as a helper drug. Here, we report on the current advances in identifying ciprofloxacin helper drugs, and put them into perspective of our own findings. We searched for potential helper drug targets in Escherichia coli strains with different levels of ciprofloxacin resistance using transcriptomics i.e., RNAseq and by deletion of genes associated with hyper-susceptibility to ciprofloxacin. Differential gene expression analysis of the highly ciprofloxacin resistant uropathogenic E. coli strain, ST131 UR40, treated with a clinically relevant concentration of ciprofloxacin (2 μg/mL), showed that the transcriptome was unaffected. Conversely, genetic screening of 23 single gene deletions in the high-level ciprofloxacin resistant laboratory derived E. coli strain, LM693, led to a significant decrease in the minimal inhibitory concentration for several genes, including genes encoding the AcrAB-To...Continue Reading

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Citations

May 10, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Alexsander Rodrigues Carvalho JuniorLuís Cláudio Nascimento da Silva
Jul 9, 2020·Computational and Structural Biotechnology Journal·Fangfang Yan, Feng Gao
Dec 5, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Natassja G BushAnthony Maxwell
Mar 13, 2019·Mutation Research. Genetic Toxicology and Environmental Mutagenesis·Mark M MuenterPenny J Beuning

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Datasets Mentioned

BETA
GSE89507

Methods Mentioned

BETA
PCR
RNA-Seq
gene-knockouts

Software Mentioned

Rockhopper

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