investigation of the mechanism of nitrofurantoin resistance in uropathogenic escherichia coli isolates

Nitrofurantoin is an antibiotic that shows good performance in treatment of urinary tract infections (utis) and is now prescribed as first-line drug in the treatment of uncomplicated lower utis. despite low resistance to this drug, the investigation of resistant uropathogenic escherichia coli strains shows mechanisms to justify the resistance in them. mutation in chromosomal genes nfsa and nfsb is the main mechanism and mutation in chromosomal gene ribe is the next mechanism of nitrofurantoin resistance and the presence of plasmid genes oqxab can increase resistance to this antibiotic. to investigate the mechanism of nitrofurantoin resistance in upec isolates, after collecting isolates, antibiogram test was performed to evaluate the sensitivity or resistance of samples to nitrofurantoin. then, minimum inhibitory concentration of the drug was determined. in order to investigate the genetic origin of nitrofurantoin resistance in terms of its plasmid or chromosomal nature, pcr was performed. the strains whose their resistance was found to be chromosomal, were sequenced and the mutations found in each of relevant genes was analysed by bioinformatics tools. none of the tested resistant isolates showed the presence of plasmid genes oqxab. the result of chromosomal genes sequencing confirmed the amino acid changes in the protein sequence of nfsa and nfsb genes. these changes in the sequence related to gene nfsa were identified in the forms of substitution mutations h11y, s39g, i117t, g126r, g130d, k141e, q147r, g187d and deletion mutations δ (w77-f79). also the changes in the sequence related to gene nfsb were identified in the forms of substitution mutations n42h, w46r, g66d, m75i, h80y, v93a, a174e. moreover, no change was observed in the amino acid sequence of the protein resulting from the gene ribe. accordingly, the occurrence of nonsynonymous mutations in chromosomal genes nfsa and nfsb were identified as the cause of nitrofurantoin resistance in resistant strains.