Escherichia coli nfsA mutations conferring resistance to nitrofurantoin

Accession ARO:3003751
CARD Short NameEcol_nfsA_NIT
DefinitionnfsA encodes the major oxygen-insesitive nitroreductase in E. coli. The first step of resistance to nitrofurazone is mutation of nfsA.
AMR Gene Familyantibiotic resistant nfsA
Drug Classnitrofuran antibiotic
Resistance Mechanismantibiotic target alteration
Resistomes with Sequence VariantsCitrobacter freundiig, Enterobacter cloacaewgs, Escherichia colig+wgs, Shigella flexnerig, Shigella sonneiwgs
Classification8 ontology terms | Show
Parent Term(s)2 ontology terms | Show
+ confers_resistance_to_antibiotic nitrofurantoin [Antibiotic]
+ antibiotic resistant nfsA [AMR Gene Family]
Publications

Sandegren L, et al. 2008. J. Antimicrob. Chemother. 62(3):495-503 Nitrofurantoin resistance mechanism and fitness cost in Escherichia coli. (PMID 18544599)

Race PR, et al. 2005. J. Biol. Chem. 280(14):13256-64 Structural and mechanistic studies of Escherichia coli nitroreductase with the antibiotic nitrofurazone. Reversed binding orientations in different redox states of the enzyme. (PMID 15684426)

Ho PL, et al. 2015. Antimicrob. Agents Chemother. 60(1):537-43 Plasmid-Mediated OqxAB Is an Important Mechanism for Nitrofurantoin Resistance in Escherichia coli. (PMID 26552976)

Resistomes

Prevalence of Escherichia coli nfsA mutations conferring resistance to nitrofurantoin among the sequenced genomes, plasmids, and whole-genome shotgun assemblies available at NCBI or IslandViewer for 414 important pathogens (see methodological details and complete list of analyzed pathogens). Values reflect percentage of genomes, plasmids, genome islands, or whole-genome shotgun assemblies that have at least one hit to the AMR detection model. Default view includes percentages calculated based on Perfect plus Strict RGI hits. Select the checkbox to view percentages based on only Perfect matches to AMR reference sequences curated in CARD (note: this excludes resistance via mutation as references in protein variant models are often wild-type, sensitive sequences).

Prevalence: protein variant model (view sequences)

SpeciesNCBI ChromosomeNCBI PlasmidNCBI WGSNCBI GIGRDI-AMR2
Citrobacter freundii1.64%0%0%0%0%
Enterobacter cloacae0%0%1.28%0%0%
Escherichia coli0.33%0%0.56%0%0.49%
Shigella flexneri1%0%0%0%0%
Shigella sonnei0%0%0.22%0%0%
Show Perfect Only


Detection Models

Model Type: protein variant model

Model Definition: Protein Variant Models (PVM) perform a similar search as Protein Homolog Models (PHM), i.e. detect protein sequences based on their similarity to a curated reference sequence, but secondarily screen query sequences for curated sets of mutations to differentiate them from antibiotic susceptible wild-type alleles. PVMs are designed to detect AMR acquired via mutation of house-keeping genes or antibiotic targets, e.g. a mutated gyrase resistant to aminocoumarin antibiotics. PVMs include a protein reference sequence (often from antibiotic susceptible wild-type alleles), a curated bit-score cut-off, and mapped resistance variants. Mapped resistance variants may include any or all of single point mutations, insertions, or deletions curated from the scientific literature. A Strict RGI match has a BLASTP bit-score above the curated BLASTP cutoff value and contains at least one curated mutation from amongst the mapped resistance variants, while a Loose RGI match has a bit-score less than the curated BLASTP bit-score cut-off but still contains at least one curated mutation from amongst the mapped resistance variants.

Bit-score Cut-off (blastP): 425

PubMed: mutation data hand curated from the scientific literature, evaluated as conferring resistance (R). CRyPTIC: mutation data acquired from the CRyPTIC catalog, evaluated as resistant (R), susceptible (S), or undetermined (U). ReSeqTB: mutation data acquired from the ReSeqTB catalog, evaluated as conferring resistance (Minimal, Moderate, High), not conferring resistance (None), or Indeterminate. WHO: mutation data acquired from the WHO 2023 catalog, evaluated as resistant (R), susceptible (S), or undetermined (U).

MutationMutation typePubMed
-MTPTIELICGHRSIRHFTDEPISEAQ1-26deletion mutation from peptide sequencePMID:26552976
R15Csingle resistance variantPMID:18544599
-nt25:tdeletion mutation from nucleotide sequencePMID:26552976
S33Rsingle resistance variantPMID:18544599
Q44Ternonsense mutationPMID:26552976
G131Dsingle resistance variantPMID:18544599
R133Ssingle resistance variantPMID:26552976
K141Ternonsense mutationPMID:26552976
-QYDEQLA191-197deletion mutation from peptide sequencePMID:26552976
R203Csingle resistance variantPMID:18544599
R203Lsingle resistance variantPMID:18544599
E233Ternonsense mutationPMID:26552976
-nt603:cdeletion mutation from nucleotide sequencePMID:26552976

>gb|AAC73938.1|+|Escherichia coli nfsA mutations conferring resistance to nitrofurantoin [Escherichia coli str. K-12 substr. MG1655]
MTPTIELICGHRSIRHFTDEPISEAQREAIINSARATSSSSFLQCSSIIRITDKALREEL
VTLTGGQKHVAQAAEFWVFCADFNRHLQICPDAQLGLAEQLLLGVVDTAMMAQNALIAAE
SLGLGGVYIGGLRNNIEAVTKLLKLPQHVLPLFGLCLGWPADNPDLKPRLPASILVHENS
YQPLDKGALAQYDEQLAEYYLTRGSNNRRDTWSDHIRRTIIKESRPFILDYLHKQGWATR



>gb|U00096.3|+|891184-891906|Escherichia coli nfsA mutations conferring resistance to nitrofurantoin [Escherichia coli str. K-12 substr. MG1655]
ATGACGCCAACCATTGAACTTATTTGTGGCCATCGCTCCATTCGCCATTTCACTGATGAACCCATTTCCGAAGCGCAGCGTGAGGCGATT
ATTAACAGCGCCCGTGCGACGTCCAGTTCCAGTTTTTTGCAGTGCAGTAGCATTATTCGCATTACCGACAAAGCGTTACGTGAAGAACTG
GTGACGCTGACCGGCGGGCAAAAACACGTAGCGCAAGCGGCGGAGTTCTGGGTGTTCTGTGCCGACTTTAACCGCCATTTACAGATCTGT
CCGGATGCTCAGCTCGGCCTGGCGGAACAACTGTTGCTCGGTGTCGTTGATACGGCAATGATGGCGCAGAATGCATTAATCGCAGCGGAA
TCGCTGGGATTGGGCGGGGTATATATCGGCGGCCTGCGCAATAATATTGAAGCGGTGACGAAACTGCTTAAATTACCGCAGCATGTTCTG
CCGCTGTTTGGGCTGTGCCTTGGCTGGCCTGCGGATAATCCGGATCTTAAGCCGCGTTTACCGGCCTCCATTTTGGTGCATGAAAACAGC
TATCAACCGCTGGATAAAGGCGCACTGGCGCAGTATGACGAGCAACTGGCGGAATATTACCTCACCCGTGGCAGCAATAATCGCCGGGAT
ACCTGGAGCGATCATATCCGCCGAACAATCATTAAAGAAAGCCGCCCATTTATTCTGGATTATTTGCACAAACAGGGTTGGGCGACGCGC
TAA

Curator Acknowledgements
Curator Description Most Recent Edit