Background Nitrofurantoin is an antibiotic that demonstrates good efficacy in the treatment of uncomplicated urinary tract infections (UTIs), especially those caused by uropathogenic Escherichia coli (UPEC). However, recent reports about the emergence of nitrofurantoin resistance in UPEC are concerning. This study aimed to investigate the genetic diversity of nitrofurantoin-resistant UPEC isolates and their characteristics. Methods In this cross-sectional study, 235 UPEC isolates collected from Ahvaz, Iran were investigated for resistance to nitrofurantoin. To evaluate the mechanism of this resistance, two groups of chromosomal genes (nfsA, nfsB, and ribE) and plasmid genes (oqxA and oqxB) were investigated by PCR. The nfsA, nfsB, and ribE genes were sequenced and variations of them were analyzed. The phenotypic and genotypic characteristics of the isolates were investigated. Results In total, six (2.55%) nitrofurantoin-resistant UPEC isolates were identified. The oqxA and oqxB genes and mutations in ribE were not detected. Several deleterious mutations in NfsA (G130D, S39G, H11Y, and ΔW77-F79), and NfsB (N42H, W46R, and H80Y), as well as several neutral mutations in both genes were detected. To our knowledge, the NfsB mutations N42H and H80Y have not been previously reported, suggesting potential novelty. All these isolates were multidrug-resistant (MDR). Although all were non-motile and non-hemolytic, some showed biofilm and cellulose production. Three isolates belonged to the B2 group, while the others belonged to the B1, A, and F groups. Pathogenicity islands (PAIs) IV536, ICFT073, IICFT073, and I536 were variably present. Incompatibility plasmid replicons Frep, FII, FIA, FIB, I1, and A/C were detected across isolates. Virulence-associated genes (VAGs) including iutA, fyuA, papG, traT, fimH, kpsMT II, papC, and afa/draBC were identified. Conclusion We concluded that in our studied isolates, deleterious mutation in chromosomal genes nfsA, nfsB, or both is likely drivers of resistance to nitrofurantoin and the changes caused by gene ribE and the presence of plasmid genes oqxAB are at the next levels of importance. Examination of the phenotypic and genetic characteristics of the isolates demonstrates that these mutations may occur in some isolates with high antimicrobial resistance and virulence, highlighting the need for broader studies to assess their epidemiological significance.

Nitrofurantoin resistance mechanisms in uropathogenic Escherichia coli isolates from Iran

期刊论文
出版模式：

开放获取
发表日期：

2025年11月5日

查看全文

Shayesteh Novin,
Seyedeh Elham Rezatofighi,
Mohammad Roayaei Ardakani

摘要

Background

Nitrofurantoin is an antibiotic that demonstrates good efficacy in the treatment of uncomplicated urinary tract infections (UTIs), especially those caused by uropathogenic Escherichia coli (UPEC). However, recent reports about the emergence of nitrofurantoin resistance in UPEC are concerning. This study aimed to investigate the genetic diversity of nitrofurantoin-resistant UPEC isolates and their characteristics.

Methods

In this cross-sectional study, 235 UPEC isolates collected from Ahvaz, Iran were investigated for resistance to nitrofurantoin. To evaluate the mechanism of this resistance, two groups of chromosomal genes (nfsA, nfsB, and ribE) and plasmid genes (oqxA and oqxB) were investigated by PCR. The nfsA, nfsB, and ribE genes were sequenced and variations of them were analyzed. The phenotypic and genotypic characteristics of the isolates were investigated.

Results

In total, six (2.55%) nitrofurantoin-resistant UPEC isolates were identified. The oqxA and oqxB genes and mutations in ribE were not detected. Several deleterious mutations in NfsA (G130D, S39G, H11Y, and ΔW77-F79), and NfsB (N42H, W46R, and H80Y), as well as several neutral mutations in both genes were detected. To our knowledge, the NfsB mutations N42H and H80Y have not been previously reported, suggesting potential novelty. All these isolates were multidrug-resistant (MDR). Although all were non-motile and non-hemolytic, some showed biofilm and cellulose production. Three isolates belonged to the B2 group, while the others belonged to the B1, A, and F groups. Pathogenicity islands (PAIs) IV₅₃₆, I_CFT073, II_CFT073, and I₅₃₆ were variably present. Incompatibility plasmid replicons Frep, FII, FIA, FIB, I1, and A/C were detected across isolates. Virulence-associated genes (VAGs) including iutA, fyuA, papG, traT, fimH, kpsMT II, papC, and afa/draBC were identified.

Conclusion

We concluded that in our studied isolates, deleterious mutation in chromosomal genes nfsA, nfsB, or both is likely drivers of resistance to nitrofurantoin and the changes caused by gene ribE and the presence of plasmid genes oqxAB are at the next levels of importance. Examination of the phenotypic and genetic characteristics of the isolates demonstrates that these mutations may occur in some isolates with high antimicrobial resistance and virulence, highlighting the need for broader studies to assess their epidemiological significance.