Deciphering the Nitrofurantoin Resistance Mechanism in Uropathogenic Enterococcus Species
DOI:
https://doi.org/10.3329/bmrcb.v52i1.88156Keywords:
Enterococcus, Efflux pump genes, Nitroreductases genes, Efflux pump inhibitorAbstract
Background: Urinary tract infection caused by Enterococcus species is of great concern both in community and hospital settings due to their increasing resistance to multiple antimicrobial agents. Nitrofurantoin is an important therapeutic option for urinary tract infection caused by Enterococcus species, whose mechanism of resistance remains to be explored.
Objectives: The aim of the study was to evaluate nitrofurantoin resistance mechanism of Enterococcus species by detection of efflux pump genes (emeA, efrA, efrB) and nitroreductase genes (ef0404, ef0648) along with effect of efflux pump inhibitors (verapamil and chlorpromazine) in nitrofurantoin resistant isolates.
Methods: Laboratory isolated Enterococcus species were identified from culture of urine specimen in Department of Microbiology and Immunology, BMU. These isolates were subjected to nitrofurantoin susceptibility tests by both broth microdilution technique and automated method (VITEK®2 Compact). Enterococcal efflux pump genes (emeA, efrA and efrB) and nitroreductase genes (ef0404, ef0648) were detected by conventional PCR. Finally, the minimum inhibitory concentrations (MICs) of nitrofurantoin with and without efflux pump inhibitors (verapamil and chlorpromazine) were determined in resistant isolates by broth microdilution method.
Results: Among the 53 Enterococcus species isolated from urine, majority were E. faecalis (81.1%). Nitrofurantoin resistant isolates were 13.2% and mostly exhibited by the rarer species. All the nitrofurantoin susceptible enterococci isolates harbored at least one of the nitroreductase genes (ef0404, 80.4% and ef0648, 91.3%) and none of the nitroreductase genes were detected in the nitrofurantoin (NIT) resistant isolates. Among all nitrofurantoin susceptible enterococcal isolates, 65.2% and 34.8% isolates carried emeA and efrAB genes respectively. Less than half (40%) of the resistant isolates harbored efflux pump genes. Effective reduction of MIC of nitrofurantoin among nitrofurantoin resistant enterococci isolates were observed in the combination of nitrofurantoin and chlorpromazine in comparison to nitrofurantoin and verapamil combination.
Conclusion: Deletions in the nitroreductases-encoding genes was the main reason for nitrofurantoin resistance in Enterococcus species. The finding of the present study would be helpful in formulating therapeutic options against Enterococcus.
Bangladesh Medical Res Counc Bull 2026;52(1): 57-62
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Copyright (c) 2026 Nadia Alam, Ismet Nigar, Imran Ahmed, Abida Sultana, Sharmeen Ahmed
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