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Novel 5-nitrofuran-activating reductase in Escherichia coli

journal contribution
posted on 2023-05-03, 21:17 authored by Vuong Le, Ieuan Davies, Christina MoonChristina Moon, David WheelerDavid Wheeler, Patrick Biggs, Jasna Rakonjac
The global spread of multidrug resistant enterobacteria warrants new strategies to combat these pathogens. One possible approach is reconsideration of “old” antimicrobials which remain effective after decades of use. Synthetic 5-nitrofurans such as furazolidone, nitrofurantoin and nitrofurazone, are such a class of antimicrobial drugs. Recent epidemiological data reported a very low prevalence of resistance to this antimicrobial class amongst clinical Escherichia coli isolates in various parts of the world, forecasting the increasing importance of its uses to battle antibiotic resistant enterobacteria. Though they have had a long history of clinical use, an understanding about the mechanism of action of 5-nitrofurans remains limited. Nitrofurans are known as prodrugs that are activated in E. coli by reduction catalyzed by two redundant nitroreductases, NfsA and NfsB. Furazolidone, nevertheless, retains relatively significant antibacterial activity in the nitroreductase-deficient (delta)nfsA (delta)nfsB E. coli strain, indicating the presence of additional activating enzymes and/or the antibacterial activity of the unreduced form. Using genome sequencing, genetic, biochemical and bioinformatic approaches, we discovered a novel 5-nitrofuran-activating enzyme, AhpF, in E. coli. Discovery of a new nitrofuran-reducing enzyme opens new avenues for overcoming 5-nitrofuran resistance, such as designing nitrofuran analogues with higher affinity for AhpF or screening for adjuvants that enhance AhpF expression.


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Copyright © 2019 American Society for Microbiology. All rights reserved


  • English

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American Society for Microbiology

Journal title

Antimicrobial Agents and Chemotherapy




Le, V. V. H., Davies, I. G., Moon, C. D., Wheeler, D., Biggs, P. J., & Rakonjac, J. (2019). Novel 5-nitrofuran-activating reductase in Escherichia coli. Antimicrobial Agents and Chemotherapy, 63(11), e00868. doi:10.1128/AAC.00868-19

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