Molecule Information

General Information of the Molecule (ID: Mol00918)

• Name: DNA gyrase subunit A (GYRA) ,Ureaplasma urealyticum
• Synonyms: UUR2_0088
• Molecule Type: Protein
• Gene Name: gyrA
• Gene ID: 45015642
• Sequence:
  MALKKPKKSRLTTEEIKQQLEGSTIKEQSITKEVETSFLDYSMSVIVARALPDVRDGFKP
  VHRRALFAAFENGMTHDKPYKKSARWVGDVIGKYHPHGDQAVYQTIVRMAQEFSMRYLLV
  DGHGNFGSIDGDSAAAMRYTEARLSKISYELLKYIDKETVDFVPNYDASEQEPSVLPSGF
  PNLLTNGTTGIAVGMATNIPPHNLTEVCQAIKAYAKNHDISIPEIMEHLKGPDFPTGAEI
  YGDSGIINYFNTGRGSVTIRSKYEIEDIGQGRVAIVVTEIPYMVNKVNLIEKIVELVTNK
  QIEGISDLRDESSRDGIRIVIEVKRDVIPEVLLNKLFKTTALQTNFSVNNLALVNGVPMV
  LNIKEMIKYYFEHQIEVLVRRTKFDLRKAKERIHIVEGLVIAVNNIDEVIKIIKASGDDD
  IASKALIARFGLTELQTKAILEMRLRALTGLNIDKLKKEYEDLLLIIEDLEDILENYDRQ
  VNIICENLDYLIEKFGDERRTEIMYGVSSHIDDEDLIPVEDIVVTMSKRGYFKRLPIDTY
  KNQRRGGVGVQGLKTYEDDDVEKILVANTHTDLLFFSDLGRVYRLRGHEVPLGSRQSKGI
  PAINFLPIEKSESILTILPIDNYEQGSLFFTTSKGIIKRANLSDFESIRANGKIAITLKE
  GDKLFSVMQTLGNDEVFIGASNGNVIRFNENDAREMGRIATGVKGINLEDDEYVVGTGLS
  SHGEYVLAVGSKGLGKLTDINDYRLTKRGAKGVNTLKVNDRTGNLVSIKVVNRDEEALII
  TTSGKVIRLSIQDISVIGRNTSGVKLISLENKEEVKSIAIFKKEEIDDNDDEQKTSHGNE
  HNLE
• Function: A type II topoisomerase that negatively supercoils closed circular double-stranded (ds) DNA in an ATP-dependent manner to modulate DNA topology and maintain chromosomes in an underwound state. Negative supercoiling favors strand separation, and DNA replication, transcription, recombination and repair, all of which involve strand separation. Also able to catalyze the interconversion of other topological isomers of dsDNA rings, including catenanes and knotted rings. Type II topoisomerases break and join 2 DNA strands simultaneously in an ATP-dependent manner.
• Uniprot ID: C0AGY7_UREUR

Kingdom: N.A.
Phylum: Tenericutes
Class: Mollicutes
Order: Mycoplasmatales
Family: Mycoplasmataceae
Genus: Ureaplasma
Species: Ureaplasma urealyticum

Type(s) of Resistant Mechanism of This Molecule

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Ciprofloxacin XR

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Ureaplasma urealyticum infection [1], [2]

• Resistant Disease: Ureaplasma urealyticum infection [ICD-11: 1A81.2]
• Resistant Drug: Ciprofloxacin XR
• Molecule Alteration: Missense mutation; p.S83L
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli k-12 JM109; 83333
• In Vitro Model: Ureaplasma parvum serovar 3 isolates; 38504
• In Vitro Model: Ureaplasma parvum serovar 6 isolates; 95660
• In Vitro Model: Ureaplasma urealyticum isolates; 2130
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Quinolones are used for treating urogenital infections and interact in bacteria with the type II topoisomerases DNA gyrase and topoisomerase IV, both of which are composed of two A and two B subunits; these subunits are encoded by the gyrA and gyrB genes for DNA gyrase and parC and parE genes for topoisomerase IV.Out of 28 clinical Ureaplasma strains, we isolated 9 with high MICs of quinolones and found a single parC gene mutation, resulting in the change S83L.

Disease Class: Ureaplasma urealyticum infection [1], [2]

• Resistant Disease: Ureaplasma urealyticum infection [ICD-11: 1A81.2]
• Resistant Drug: Ciprofloxacin XR
• Molecule Alteration: Missense mutation; p.S83L
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli k-12 JM109; 83333
• In Vitro Model: Ureaplasma parvum serovar 3 isolates; 38504
• In Vitro Model: Ureaplasma parvum serovar 6 isolates; 95660
• In Vitro Model: Ureaplasma urealyticum isolates; 2130
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Quinolones are used for treating urogenital infections and interact in bacteria with the type II topoisomerases DNA gyrase and topoisomerase IV, both of which are composed of two A and two B subunits; these subunits are encoded by the gyrA and gyrB genes for DNA gyrase and parC and parE genes for topoisomerase IV.Out of 28 clinical Ureaplasma strains, we isolated 9 with high MICs of quinolones and found a single parC gene mutation, resulting in the change S83L.

References

• Ref 1: In vitro activity of five quinolones and analysis of the quinolone resistance-determining regions of gyrA, gyrB, parC, and parE in Ureaplasma parvum and Ureaplasma urealyticum clinical isolates from perinatal patients in Japan. Antimicrob Agents Chemother. 2015 Apr;59(4):2358-64. doi: 10.1128/AAC.04262-14. Epub 2015 Feb 2.
• Ref 2: Analysis of mutations in DNA gyrase and topoisomerase IV of Ureaplasma urealyticum and Ureaplasma parvum serovars resistant to fluoroquinolones. Infect Genet Evol. 2017 Jan;47:64-67. doi: 10.1016/j.meegid.2016.11.019. Epub 2016 Nov 21.