Fluoroquinolone-associated mutations in soxS, a transcriptional regulator of AcrAB efflux pump
Type of Degreethesis
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Escherichia coli is a major cause of urinary tract infections in companion animals and efflux pump over expression has been associated with high-level fluoroquinolone (FQ) resistance. The purpose of this study was to evaluate the impact of in vitro exposure of different generations of fluoroquinolones on the mutability of soxS in clinical canine E.coli isolates and to evaluate the impact of these mutations on the expression of AcrAB and EmrE efflux pumps. Broth macrodilution was performed to expose SDR, NDR, MDR and ATCC isolates to 2-64 X their FQ MIC for 30, 60, 90 and 120 minutes. Amplification and sequencing of soxS revealed the presence of three novel mutations (M78K, Q56K, L59R) when exposing SDR, NDR and ATCC isolates to 0.06 and 0.12µg/mL of ciprofloxacin for 30, 60 and 90 minutes. No mutations were identified in isolates exposed to newer generation FQs. Overexpression of acrB was identified at concentrations and time points that had previously induced soxS mutations. An increase, but not overexpresssion occurred in emrE of ciprofloxacin exposed isolates. This study will contribute to the accumulated knowledge regarding mechanisms whereby fluoroquinolones cause MDR, thus providing evidence for selecting one antimicrobial over another.
- Thesis Lazzaroni Final Nov .pdf