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  1. The FDA Science Forum

2021 FDA Science Forum

Mechanisms of Resistance to Fluoroquinolone Antibiotic in Uropathogenic Escherichia Coli

Authors:
Poster Author(s)
Nawaz, Mohamed, FDA/NCTR
Sung, Kidon, FDA/NCTR
Khan, Saeed, FDA/NCTR
Marasa, Bernard, FDA/CDER
Nguyen, Kiet, FDA/CDER
Center:
Contributing Office
National Center for Toxicological Research

Abstract

Poster Abstract

Urinary tract infections (UTI) is a bacterial infection of the urogenitals and mostly caused by uropathogenic Escherichia coli (UPECs). Antibiotics such as fluoroquinolones (FQ) were used in the treatment of UPECs. Misuse of FQ in the treatment of UTI may have resulted in the prevalence of FQ-resistant UPECs. The occurrence and prevalence of antibiotic-resistant pathogenic UPECs in clinical ecosystem is considered as a threat to the efficacy of the antibiotic and public health by the USFDA and many other regulatory agencies. A study was undertaken to characterize FQ-resistant UPEC isolates and the mutations in the quinolone-resistant-determining regions (QRDR) of the isolates that confer resistance to FQ antibiotics. Twenty three of the 104 UPEC isolated from patients with UTI were resistant to FQ antibiotics. Purified PCR amplicons of gyrA and parC genes from the total DNA of the isolates were partially sequenced and analyzed for point mutations that confer resistance to FQ antibiotics. Sequence analysis indicated that simultaneous point mutations in the QRDR of gyrA (at position 83Ser→Leu and 87Asp→Asn) accompanied by point mutations in the QRDR of parC (80Ser→Ile or 84Glu→Val) were responsible for conferring resistance to FQ antibiotics in these isolates. Efflux pumps (EPs) that dilute the accumulation of the antibiotic inside the cell was determined by the ethidium bromide accumulation and measurement of the relative fluorescence units (RFUs). All FQ-resistant UPECs had EP activity. The EP activities were higher in FQ-resistant UPECs than antibiotic sensitive strains of UPECs. Our results indicate that point mutations in the QRDR of gyrA and parC coupled with EP mechanisms may contribute to FQ resistance in UPECs.


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