Clostridioides difficile gyrA conferring resistance to fluoroquinolones

Accession ARO:3003995
CARD Short NameCdif_gyrA_FLO
DefinitionAmino acid substitutions in Clostridioides difficile gyrase subunit A which when present confer functional resistance to fluoroquinolone antibiotics.
AMR Gene Familyfluoroquinolone resistant gyrA
Drug Classfluoroquinolone antibiotic
Resistance Mechanismantibiotic target alteration
Classification11 ontology terms | Show
Parent Term(s)6 ontology terms | Show
+ fluoroquinolone resistant gyrA [AMR Gene Family]
+ confers_resistance_to_antibiotic levofloxacin [Antibiotic]
+ confers_resistance_to_antibiotic moxifloxacin [Antibiotic]
+ confers_resistance_to_antibiotic ofloxacin [Antibiotic]
+ confers_resistance_to_antibiotic ciprofloxacin [Antibiotic]
+ confers_resistance_to_antibiotic gatifloxacin [Antibiotic]
Publications

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)

Ackermann G, et al. 2001. Antimicrob. Agents Chemother. 45(8):2348-53 Resistance to moxifloxacin in toxigenic Clostridium difficile isolates is associated with mutations in gyrA. (PMID 11451695)

Carman RJ, et al. 2009. Anaerobe 15(6):244-8 Diversity of moxifloxacin resistance during a nosocomial outbreak of a predominantly ribotype ARU 027 Clostridium difficile diarrhea. (PMID 19818865)

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)

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)

Ackermann G, et al. 2003. Clin. Microbiol. Infect. 9(6):526-30 Antecedent use of fluoroquinolones is associated with resistance to moxifloxacin in Clostridium difficile. (PMID 12848728)

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)

Spigaglia P, et al. 2009. Antimicrob. Agents Chemother. 53(6):2463-8 Molecular analysis of the gyrA and gyrB quinolone resistance-determining regions of fluoroquinolone-resistant Clostridium difficile mutants selected in vitro. (PMID 19364867)

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)

Resistomes

Prevalence of Clostridioides difficile gyrA conferring resistance to fluoroquinolones among the sequenced genomes, plasmids, and whole-genome shotgun assemblies available at NCBI or IslandViewer for 413 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

SpeciesNCBI ChromosomeNCBI PlasmidNCBI WGSNCBI GI
No prevalence data


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): 1500

Legend:

  • discovered in clinical, agricultural, or environmental isolates

  • discovered via laboratory selection experiments

  • ReSeqTB https://platform.reseqtb.org

Published Variants:

PMID: 27842877L345I A384D
PMID: 19818865C245T
PMID: 12384345D71V T82V T82I A118T
PMID: 12848728T83I
PMID: 22508299D71G D81N T82A R90K D103N Q123K
PMID: 19364867A118S,T82A A92E A118S
PMID: 20226332P116A

>gb|CAJ66820.1|+|Clostridioides difficile gyrA conferring resistance to fluoroquinolones [Clostridioides difficile 630]
MEENNKILPIEIAEEMKKSYIDYSMSVIAGRALPDVRDGLKPVHRRILYSMSELNLTPDK
PYRKSARIVGDVLGKYHPHGDTAVYYAMVRMAQDFSTRALLVDGHGNFGSVDGDSPAAMR
YTEAKMSKLSLELLRDIEKETVDFKPNFDESLKEPSVLPARYPNLLVNGSNGIAVGMATS
IPPHNLAEVIDATVYLIDNPECSVDDLIKFVQGPDFPTAAIIMGKESIAEAYRTGRGKVK
VRSRAFIEELPKGKQQIIVTEIPYQVNKAKLVERIAELVKEKRIEGISDLRDESNRNGMR
IVIELKRDANANIVLNNLYKHSQMEDTFSIIMLALVDGQPRVLNLKQILYHYIKHQEDVV
TRRTKFELNKAEARAHILEGLKIALDNIDAVISLIRASKTGQEAKLGLIEKFKLTEIQAQ
AILDMRLQRLTGLERDKIEAEYEDLIKKINRLKEILADERLLLNVIKDEITIIKENYSDE
RRTEIRHAEGEIDMRDLISDEEIAITLTHFGYIKRLPSDTYKSQKRGGRGISALTTREED
FVRHLVTTTTHSRLLFFTNKGRVFKLNAYEIPEGKRQAKGTAIVNLLQLSADEKIATLIP
IDGNDENEYLLLATKKGIVKKTKREEFKNINKSGLIAIGLRDDDELIGVELTDGKQEVLL
VTKEGMSIRFDENDIRYMGRTAMGVKGITLSKEDFVVSMNLCSKGTDVLVVSKNGFGKRT
NIEEYRSQIRAGKGIKTYNISEKTGTIVGADMVNEDDEIMIINSDGVLIRIRVNEISLFG
RVTSGVKLMKTNDEVNVVSIAKINIEEE



>gb|AM180355.1|+|6066-8492|Clostridioides difficile gyrA conferring resistance to fluoroquinolones [Clostridioides difficile 630]
ATGGAAGAAAATAACAAAATACTCCCTATTGAAATAGCGGAAGAAATGAAAAAATCGTATATTGATTATTCAATGAGTGTTATAGCTGGA
CGTGCTCTTCCTGATGTTAGAGATGGTTTAAAGCCAGTTCATAGAAGAATATTATATTCAATGAGTGAGTTAAATTTAACTCCAGATAAA
CCATACAGGAAGTCAGCTCGTATTGTTGGGGACGTTTTAGGTAAGTACCATCCTCATGGAGATACTGCTGTTTATTATGCTATGGTAAGA
ATGGCACAAGATTTTTCAACTAGAGCACTTTTAGTAGATGGTCATGGTAACTTTGGTTCTGTTGATGGGGATTCACCAGCTGCTATGCGT
TATACAGAAGCTAAAATGAGTAAATTATCATTAGAACTACTGAGAGATATTGAAAAGGAAACTGTAGACTTTAAACCAAACTTTGATGAG
TCGTTAAAAGAGCCTTCAGTATTGCCAGCTAGATATCCTAATTTATTAGTAAATGGCTCAAATGGTATAGCTGTTGGTATGGCAACTTCA
ATACCTCCACATAATTTAGCAGAAGTAATTGATGCAACTGTATATTTGATAGATAATCCAGAGTGTAGTGTAGATGATTTAATAAAATTT
GTTCAAGGACCAGATTTCCCTACAGCTGCAATTATAATGGGAAAAGAAAGTATAGCAGAAGCATACAGAACTGGAAGAGGAAAAGTTAAA
GTTAGGTCTAGAGCTTTTATAGAAGAGCTACCAAAAGGAAAACAGCAAATAATAGTTACAGAAATACCTTATCAAGTAAATAAGGCTAAA
CTGGTTGAAAGAATAGCAGAGTTAGTTAAAGAAAAGAGAATAGAAGGTATATCAGACCTAAGAGACGAAAGTAATAGAAATGGTATGAGA
ATTGTTATAGAATTAAAGAGGGATGCTAATGCTAATATAGTATTAAATAATTTGTATAAACATTCTCAAATGGAAGATACTTTTAGTATA
ATAATGCTTGCACTTGTAGATGGTCAGCCAAGAGTTTTAAATCTTAAACAAATATTATATCATTATATTAAACATCAAGAAGATGTTGTT
ACAAGAAGAACTAAATTTGAACTAAATAAAGCTGAAGCAAGAGCACATATTTTAGAAGGATTAAAGATTGCTTTAGATAATATAGATGCT
GTTATAAGCTTGATAAGAGCTTCAAAGACTGGGCAAGAAGCTAAGCTAGGTTTAATAGAAAAATTCAAATTAACTGAAATCCAAGCACAA
GCTATATTAGATATGAGACTTCAAAGACTTACAGGTTTAGAAAGAGATAAGATAGAAGCTGAATATGAAGATTTAATCAAGAAGATAAAT
AGATTAAAAGAGATTTTAGCTGATGAAAGATTACTTTTAAATGTAATAAAGGATGAAATTACAATAATAAAAGAAAATTACTCTGATGAG
AGAAGAACAGAAATAAGACATGCTGAAGGCGAAATAGATATGAGAGATCTTATAAGTGATGAAGAAATAGCAATAACTCTTACTCACTTT
GGATATATAAAAAGGCTTCCATCTGATACTTATAAGAGTCAAAAAAGGGGTGGAAGAGGTATTTCAGCACTTACAACTAGAGAAGAAGAT
TTTGTAAGGCACTTGGTAACTACAACTACTCATAGTAGACTATTATTCTTTACAAATAAAGGTAGAGTATTTAAATTAAATGCATATGAA
ATACCAGAAGGTAAGAGACAGGCTAAAGGTACTGCTATAGTGAATTTACTTCAATTGTCAGCAGATGAGAAAATTGCTACTCTAATACCT
ATTGATGGTAATGATGAAAATGAATATTTATTACTTGCAACGAAAAAAGGTATTGTTAAAAAGACTAAGAGAGAAGAGTTCAAAAATATA
AATAAATCTGGTCTTATTGCAATAGGTTTAAGAGATGATGATGAGCTTATTGGAGTAGAACTTACAGATGGAAAACAAGAAGTACTTTTA
GTAACTAAAGAAGGTATGTCTATAAGATTTGATGAAAATGATATAAGATATATGGGTAGAACAGCAATGGGTGTAAAAGGTATAACTTTA
AGTAAAGAAGATTTTGTTGTGTCTATGAACCTTTGTAGTAAAGGTACAGATGTGTTAGTTGTAAGTAAGAATGGTTTTGGAAAGAGAACA
AATATAGAAGAGTATAGAAGTCAAATAAGAGCTGGTAAAGGAATTAAAACTTATAATATATCTGAAAAAACTGGTACAATTGTAGGTGCA
GATATGGTCAACGAAGATGATGAGATAATGATTATAAATTCTGATGGAGTTCTTATTAGAATAAGAGTCAATGAAATATCACTGTTTGGA
AGAGTTACAAGTGGTGTTAAATTAATGAAGACGAATGATGAAGTCAATGTAGTTTCGATTGCCAAAATAAATATTGAAGAAGAATAG