Clostridioides difficile gyrB conferring resistance to fluoroquinolones

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Accession ARO:3004562
CARD Short NameCdif_gyrB_FLO
DefinitionPoint mutations in gyrB of Clostridioides difficile conferring resistance to fluoroquinolone antibiotics.
AMR Gene Familyfluoroquinolone resistant gyrB
Drug Classfluoroquinolone antibiotic
Resistance Mechanismantibiotic target alteration
Resistomes with Sequence VariantsClostridium botulinumg+wgs, Clostridium butyricumg+wgs, Clostridium sporogenesg+wgs, Clostridium tetanig+wgs
Classification11 ontology terms | Show
Parent Term(s)5 ontology terms | Show
+ confers_resistance_to_antibiotic ciprofloxacin [Antibiotic]
+ confers_resistance_to_antibiotic levofloxacin [Antibiotic]
+ confers_resistance_to_antibiotic moxifloxacin [Antibiotic]
+ fluoroquinolone resistant gyrB [AMR Gene Family]
+ confers_resistance_to_antibiotic gemifloxacin [Antibiotic]
Publications

Dridi L, et al. 2002. Antimicrob. Agents Chemother. 46(11):3418-21 gyrA and gyrB mutations are implicated in cross-resistance to Ciprofloxacin and moxifloxacin in Clostridium difficile. (PMID 12384345)

Walkty A, et al. 2010. Diagn. Microbiol. Infect. Dis. 66(4):419-24 Molecular characterization of moxifloxacin resistance from Canadian Clostridium difficile clinical isolates. (PMID 20226332)

Spigaglia P, et al. 2008. J. Med. Microbiol. 57(Pt 6):784-9 Fluoroquinolone resistance in Clostridium difficile isolates from a prospective study of C. difficile infections in Europe. (PMID 18480338)

Liao CH, et al. 2012. Antimicrob. Agents Chemother. 56(7):3943-9 Characterizations of clinical isolates of clostridium difficile by toxin genotypes and by susceptibility to 12 antimicrobial agents, including fidaxomicin (OPT-80) and rifaximin: a multicenter study in Taiwan. (PMID 22508299)

Mac Aogáin M, et al. 2015. J Glob Antimicrob Resist 3(4):295-299 Identification of a novel mutation at the primary dimer interface of GyrA conferring fluoroquinolone resistance in Clostridium difficile. (PMID 27842877)
Resistomes

Prevalence of Clostridioides difficile gyrB conferring resistance to fluoroquinolones 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
Clostridium botulinum97.01%0%99.18%0%0%
Clostridium butyricum66.67%0%98.04%0%0%
Clostridium sporogenes100%0%100%0%0%
Clostridium tetani50%0%100%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): 1000

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
V130Isingle resistance variantPMID:27842877
I139Rsingle resistance variantPMID:27842877
S366Vsingle resistance variantPMID:27842877
S366Asingle resistance variantPMID:27842877
R377Gsingle resistance variantPMID:22508299
R389Psingle resistance variantPMID:22508299
E399Ksingle resistance variantPMID:22508299
D409Nsingle resistance variantPMID:22508299
S416Asingle resistance variantPMID:18480338
V423Fsingle resistance variantPMID:22508299
D426Nsingle resistance variantPMID:12384345
D426Vsingle resistance variantPMID:18480338
K444Fsingle resistance variantPMID:20226332
R447Lsingle resistance variantPMID:12384345
R447Ksingle resistance variantPMID:18480338
R457Tsingle resistance variantPMID:22508299
S464Tsingle resistance variantPMID:27842877
D465Ysingle resistance variantPMID:22508299
E466Ksingle resistance variantPMID:22508299
E466Vsingle resistance variantPMID:20226332

>gb|ADK13120.1|+|Clostridioides difficile gyrB conferring resistance to fluoroquinolones [Clostridium ljungdahlii DSM 13528]
MMQEKKQTYDENQIQVLEGLEAVRKRPGMYIGSTSSRGLHHLVYEIVDNSIDEALAGYCD
KINVIIHKDNSITVTDNGRGMPVGMHHKMKKPTVEVIMTILHAGGKFGGGGYKVSGGLHG
VGASVVNALSEICEVEVKRESHIWRQVFKRGKVASGLDIIGDSEEHGTKIHFKPDAEIFD
EIEYDYDTLAQRLRELAFLNKGIKIRLEDERDDKEEIFHYEGGIKSFVTYLNRNKQPIHK
EPIYVEGKKDDYSVEIAIQYNDGYTENIFAFANNIDTVEGGTHLAGFKSALTRVFNDYAK
KFGILKENDKNLSGEDIREGLTAVISVKLVDPQFEGQTKTKLGNSEVRGIVDSIMGESLN
NFLQENPQVAKMILDKSLMASRAREAARKARELTRRKSILENTSLPGKLADCSSKDPSEC
EIYLVEGDSAGGSAKQGRNRKFQAILPLRGKIMNVEKQRLDKILGYEEIRAMITAFGAGI
GKDFDVNKIRYNKIIIMTDADVDGAHIRTLLLTFFFRYMKELVEKCHVYIAQPPLYRVAK
GKKEYYAYSDDELDVLLTEIGGKDSNVDIQRYKGLGEMDSEQLWDTTMNPETRTLIQVNV
EDTMAADEIFTILMGDKVEPRRNFIQENAKKVVNLDI


>gb|CP001666.1|+|4517-6430|Clostridioides difficile gyrB conferring resistance to fluoroquinolones [Clostridium ljungdahlii DSM 13528]
ATGATGCAAGAAAAAAAGCAAACTTATGATGAAAATCAAATACAAGTATTAGAAGGTCTTGAAGCTGTTAGAAAAAGACCTGGAATGTAT
ATTGGAAGTACTAGTTCTAGGGGGCTTCATCATTTAGTGTATGAGATAGTTGATAATAGCATAGATGAGGCATTGGCAGGATATTGCGAT
AAAATAAATGTAATTATACATAAAGATAATTCTATAACAGTTACGGATAATGGTAGAGGAATGCCTGTTGGAATGCACCATAAAATGAAG
AAACCAACTGTAGAAGTTATAATGACTATACTACATGCAGGAGGGAAATTTGGTGGTGGAGGATACAAAGTTTCCGGCGGACTTCATGGA
GTTGGAGCATCAGTTGTAAATGCTTTATCTGAAATCTGTGAAGTTGAAGTAAAAAGAGAAAGCCATATATGGAGACAGGTATTTAAAAGA
GGAAAAGTAGCAAGCGGACTTGACATAATAGGTGATAGTGAGGAGCACGGAACAAAAATTCACTTTAAACCAGATGCAGAAATATTTGAT
GAAATAGAATATGATTATGATACATTGGCTCAAAGGCTTAGAGAATTGGCATTTTTAAACAAGGGTATAAAAATAAGGTTAGAAGATGAG
AGAGATGATAAAGAAGAAATATTTCACTATGAAGGTGGAATAAAGTCCTTTGTAACTTATCTTAATAGAAATAAACAACCAATTCATAAA
GAGCCTATATACGTAGAAGGCAAAAAAGATGACTACTCTGTAGAAATTGCTATTCAATACAATGATGGGTATACTGAAAATATTTTTGCT
TTTGCTAATAACATAGATACAGTAGAAGGTGGAACTCATTTAGCTGGATTTAAGTCAGCACTTACTAGAGTATTTAATGATTATGCAAAA
AAATTTGGTATATTAAAAGAAAATGATAAGAACCTATCAGGAGAAGATATAAGGGAAGGCCTTACTGCAGTTATATCTGTAAAACTTGTA
GACCCTCAATTTGAAGGCCAGACGAAAACAAAACTAGGAAATAGTGAAGTGCGTGGTATAGTTGACAGCATAATGGGAGAGTCCTTAAAT
AATTTTTTACAGGAAAATCCTCAAGTAGCAAAGATGATACTTGATAAATCACTTATGGCATCACGTGCTAGAGAAGCGGCAAGAAAAGCA
AGAGAGCTTACAAGACGTAAATCTATACTTGAAAATACTTCTCTTCCAGGAAAATTAGCAGATTGTTCATCTAAAGATCCTTCTGAATGT
GAAATATATTTAGTCGAGGGTGATTCTGCAGGTGGATCTGCAAAACAAGGTAGAAATAGAAAATTTCAAGCTATACTTCCGCTACGTGGT
AAAATAATGAATGTTGAGAAACAAAGGCTTGACAAAATACTTGGCTATGAAGAAATAAGAGCTATGATAACGGCATTTGGAGCAGGTATA
GGAAAAGACTTTGATGTAAATAAAATAAGATACAATAAAATAATAATAATGACAGATGCAGATGTAGATGGTGCGCACATAAGAACATTA
TTACTTACTTTTTTCTTCAGATATATGAAGGAACTTGTTGAAAAATGTCACGTTTATATAGCTCAACCACCTTTATATAGAGTAGCTAAA
GGGAAGAAGGAATACTACGCATATTCAGATGATGAATTAGATGTATTGCTTACTGAAATAGGTGGGAAAGACAGTAATGTAGATATACAA
AGATATAAAGGACTTGGAGAAATGGATTCAGAGCAACTTTGGGATACTACAATGAATCCTGAAACAAGGACTCTTATTCAAGTAAATGTA
GAGGACACTATGGCTGCTGATGAAATCTTTACTATACTTATGGGTGACAAGGTAGAACCTCGTAGAAATTTTATACAAGAAAATGCTAAA
AAAGTTGTAAACTTAGATATATAA

Curator Acknowledgements
Curator Description Most Recent Edit