Molecule Information

General Information of the Molecule (ID: Mol02147)

• Name: DNA gyrase subunit A (GYRA) ,Bacillus cereus
• Synonyms: gyrA GBAA_0006
• Molecule Type: Protein
• Gene Name: gyrA
• Gene ID: 45020040
• Sequence:
  MSDNQQQARIREINISHEMRTSFLDYAMSVIVSRALPDVRDGLKPVHRRVLYAMNDLGIT
  ADKAYKKSARIVGEVIGKYHPHGDSAVYETMVRMAQDFSQRYMLVDGHGNFGSVDGDSAA
  AMRYTEARMSKISMELIRDISKNTIDYQDNYDGSEREPIVLPARFPNLLVNGTTGIAVGM
  ATNIPPHQLGEVIDGVLALSHNPDITIAELMECIPGPDFPTAGLILGRSGIRRAYETGRG
  SIILRAKVEIEEKSNGKQSIIVTELPYQVNKARLIEKIAELVRDKKIEGITDLRDESDRN
  GMRIVMEVRRDANANVLLNNLYKHTALQTSFGINMLSLVNGEPQVLNLKQNLYHYLEHQK
  VVIRRRTAYELEKAEARAHILEGLRIALDHLDEVITLIRSSKTAEIAKQGLMERFGLSEK
  QAQAILDMRLQRLTGLEREKIEQEYQDLMKLIAELKAILADEEKVLEIIREELTEVKERF
  NDKRRTEITIGGMESIEDEDLIPEQNIAITLTHNGYIKRLPASTYKTQNRGGRGVQGMGT
  NDDDFVEHLLTTSTHDHILFFTNKGKVYRTKGYEIPEYSRTAKGIPIINLLGVDKGEWIN
  AIIPIREFGDDEFLFFTTKQGISKRTPLSSFANIRTNGLIAISLREEDEVISVRLTSGDK
  DIIVGTSNGMLIRFNEQDVRSMGRNAAGVKAITLGEEDQVVGMEIVEEDVNVLIVTKNGY
  GKRTPIDEYRLQSRGGKGLKTCNITDKNGKLVAVKSVTGEEDIMLITAAGVIIRMPVDQI
  SQMGRNTQGVRLIRLEDEQEVATVAKAQKDDEEETSEEVSSEE
• 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: A0A6H3A7B1_BACAN

Kingdom: N.A.
Phylum: Firmicutes
Class: Bacilli
Order: Bacillales
Family: Bacillaceae
Genus: Bacillus
Species: Bacillus cereus

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) 2 drug(s) in total

Ciprofloxacin XR

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Anthrax [1]

• Resistant Disease: Anthrax [ICD-11: 1B97.0]
• Resistant Drug: Ciprofloxacin XR
• Molecule Alteration: Mutation; p.S85+p.S85F+p.E89K+p.E89A
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli strain; 562
• In Vitro Model: Bacillus anthracis strain; 1392
• Experiment for Molecule Alteration: DNA cleavage assay
• Mechanism Description: The most common gyrase mutations in quinolone-resistant strains of B. anthracis are found at the conserved serine and glutamic acid residues (GyrAS85 and GyrAE89). In laboratory strains selected for resistance against ciprofloxacin and/or moxifloxacin (two widely prescribed quinolone antibacterials), approximately 80% of the isolates carried a GyrAS85L mutation (either alone or in combination with other gyrase/topoisomerase IV amino acid changes). The only other mutation reported to cause resistance without any other gyrase/topoisomerase IV changes was a GyrAE89K substitution.

Moxifloxacin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Anthrax [1]

• Resistant Disease: Anthrax [ICD-11: 1B97.0]
• Resistant Drug: Moxifloxacin
• Molecule Alteration: Mutation; p.S85+p.S85F+p.E89K+p.E89A
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli strain; 562
• In Vitro Model: Bacillus anthracis strain; 1392
• Experiment for Molecule Alteration: DNA cleavage assay
• Mechanism Description: The most common gyrase mutations in quinolone-resistant strains of B. anthracis are found at the conserved serine and glutamic acid residues (GyrAS85 and GyrAE89). In laboratory strains selected for resistance against ciprofloxacin and/or moxifloxacin (two widely prescribed quinolone antibacterials), approximately 80% of the isolates carried a GyrAS85L mutation (either alone or in combination with other gyrase/topoisomerase IV amino acid changes). The only other mutation reported to cause resistance without any other gyrase/topoisomerase IV changes was a GyrAE89K substitution.

Investigative Drug(s) 8 drug(s) in total

3'-(AM)P-dione {3-amino-7-[(3S)-3-(aminomethyl)-1-pyrrolidinyl]-1-cyclopropyl-6-fluoro-8-methyl-2,4(1H,3H)-quinazolinedione}

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Anthrax [1]

• Resistant Disease: Anthrax [ICD-11: 1B97.0]
• Resistant Drug: 3'-(AM)P-dione {3-amino-7-[(3S)-3-(aminomethyl)-1-pyrrolidinyl]-1-cyclopropyl-6-fluoro-8-methyl-2,4(1H,3H)-quinazolinedione}
• Molecule Alteration: Mutation; p.S85+p.S85F+p.E89K+p.E89A
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli strain; 562
• In Vitro Model: Bacillus anthracis strain; 1392
• Experiment for Molecule Alteration: DNA cleavage assay
• Mechanism Description: The most common gyrase mutations in quinolone-resistant strains of B. anthracis are found at the conserved serine and glutamic acid residues (GyrAS85 and GyrAE89). In laboratory strains selected for resistance against ciprofloxacin and/or moxifloxacin (two widely prescribed quinolone antibacterials), approximately 80% of the isolates carried a GyrAS85L mutation (either alone or in combination with other gyrase/topoisomerase IV amino acid changes). The only other mutation reported to cause resistance without any other gyrase/topoisomerase IV changes was a GyrAE89K substitution.

3'-(AM)P-quinolone {1-cyclopropyl-6-fluoro-1,4-dihydro-8-methyl-7-[(3S)-3-(aminomethyl)-1-pyrrolidinyl]-4-oxo-3-quinolinecarboxylic acid}

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Anthrax [1]

• Resistant Disease: Anthrax [ICD-11: 1B97.0]
• Resistant Drug: 3'-(AM)P-quinolone {1-cyclopropyl-6-fluoro-1,4-dihydro-8-methyl-7-[(3S)-3-(aminomethyl)-1-pyrrolidinyl]-4-oxo-3-quinolinecarboxylic acid}
• Molecule Alteration: Mutation; p.S85+p.S85F+p.E89K+p.E89A
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli strain; 562
• In Vitro Model: Bacillus anthracis strain; 1392
• Experiment for Molecule Alteration: DNA cleavage assay
• Mechanism Description: The most common gyrase mutations in quinolone-resistant strains of B. anthracis are found at the conserved serine and glutamic acid residues (GyrAS85 and GyrAE89). In laboratory strains selected for resistance against ciprofloxacin and/or moxifloxacin (two widely prescribed quinolone antibacterials), approximately 80% of the isolates carried a GyrAS85L mutation (either alone or in combination with other gyrase/topoisomerase IV amino acid changes). The only other mutation reported to cause resistance without any other gyrase/topoisomerase IV changes was a GyrAE89K substitution.

8-H-moxi {1-cyclopropyl-6-fluoro-1,4-dihydro-7-[(4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]-4-oxo-3-quinolinecarboxylic acid}

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Anthrax [1]

• Resistant Disease: Anthrax [ICD-11: 1B97.0]
• Resistant Drug: 8-H-moxi {1-cyclopropyl-6-fluoro-1,4-dihydro-7-[(4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]-4-oxo-3-quinolinecarboxylic acid}
• Molecule Alteration: Mutation; p.S85+p.S85F+p.E89K+p.E89A
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli strain; 562
• In Vitro Model: Bacillus anthracis strain; 1392
• Experiment for Molecule Alteration: DNA cleavage assay
• Mechanism Description: The most common gyrase mutations in quinolone-resistant strains of B. anthracis are found at the conserved serine and glutamic acid residues (GyrAS85 and GyrAE89). In laboratory strains selected for resistance against ciprofloxacin and/or moxifloxacin (two widely prescribed quinolone antibacterials), approximately 80% of the isolates carried a GyrAS85L mutation (either alone or in combination with other gyrase/topoisomerase IV amino acid changes). The only other mutation reported to cause resistance without any other gyrase/topoisomerase IV changes was a GyrAE89K substitution.

8-methoxy-cipro [1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-(1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Anthrax [1]

• Resistant Disease: Anthrax [ICD-11: 1B97.0]
• Resistant Drug: 8-methoxy-cipro [1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-(1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid]
• Molecule Alteration: Mutation; p.S85+p.S85F+p.E89K+p.E89A
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli strain; 562
• In Vitro Model: Bacillus anthracis strain; 1392
• Experiment for Molecule Alteration: DNA cleavage assay
• Mechanism Description: The most common gyrase mutations in quinolone-resistant strains of B. anthracis are found at the conserved serine and glutamic acid residues (GyrAS85 and GyrAE89). In laboratory strains selected for resistance against ciprofloxacin and/or moxifloxacin (two widely prescribed quinolone antibacterials), approximately 80% of the isolates carried a GyrAS85L mutation (either alone or in combination with other gyrase/topoisomerase IV amino acid changes). The only other mutation reported to cause resistance without any other gyrase/topoisomerase IV changes was a GyrAE89K substitution.

8-methyl-cipro [1-cyclopropyl-6-fluoro-1,4-dihydro-8-methyl-7-(1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Anthrax [1]

• Resistant Disease: Anthrax [ICD-11: 1B97.0]
• Resistant Drug: 8-methyl-cipro [1-cyclopropyl-6-fluoro-1,4-dihydro-8-methyl-7-(1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid]
• Molecule Alteration: Mutation; p.S85+p.S85F+p.E89K+p.E89A
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli strain; 562
• In Vitro Model: Bacillus anthracis strain; 1392
• Experiment for Molecule Alteration: DNA cleavage assay
• Mechanism Description: The most common gyrase mutations in quinolone-resistant strains of B. anthracis are found at the conserved serine and glutamic acid residues (GyrAS85 and GyrAE89). In laboratory strains selected for resistance against ciprofloxacin and/or moxifloxacin (two widely prescribed quinolone antibacterials), approximately 80% of the isolates carried a GyrAS85L mutation (either alone or in combination with other gyrase/topoisomerase IV amino acid changes). The only other mutation reported to cause resistance without any other gyrase/topoisomerase IV changes was a GyrAE89K substitution.

8-methyl-moxi {1-cyclopropyl-6-fluoro-1,4-dihydro-8-methyl-7-[(4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]-4-oxo-3-quinolinecarboxylic acid}

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Anthrax [1]

• Resistant Disease: Anthrax [ICD-11: 1B97.0]
• Resistant Drug: 8-methyl-moxi {1-cyclopropyl-6-fluoro-1,4-dihydro-8-methyl-7-[(4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]-4-oxo-3-quinolinecarboxylic acid}
• Molecule Alteration: Mutation; p.S85+p.S85F+p.E89K+p.E89A
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli strain; 562
• In Vitro Model: Bacillus anthracis strain; 1392
• Experiment for Molecule Alteration: DNA cleavage assay
• Mechanism Description: The most common gyrase mutations in quinolone-resistant strains of B. anthracis are found at the conserved serine and glutamic acid residues (GyrAS85 and GyrAE89). In laboratory strains selected for resistance against ciprofloxacin and/or moxifloxacin (two widely prescribed quinolone antibacterials), approximately 80% of the isolates carried a GyrAS85L mutation (either alone or in combination with other gyrase/topoisomerase IV amino acid changes). The only other mutation reported to cause resistance without any other gyrase/topoisomerase IV changes was a GyrAE89K substitution.

Cipro-dione [3-amino-7-(1-piperazinyl)-1-cyclopropyl-6-fluoro-2,4(1H,3H)-quinazolinedione]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Anthrax [1]

• Resistant Disease: Anthrax [ICD-11: 1B97.0]
• Resistant Drug: Cipro-dione [3-amino-7-(1-piperazinyl)-1-cyclopropyl-6-fluoro-2,4(1H,3H)-quinazolinedione]
• Molecule Alteration: Mutation; p.S85+p.S85F+p.E89K+p.E89A
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli strain; 562
• In Vitro Model: Bacillus anthracis strain; 1392
• Experiment for Molecule Alteration: DNA cleavage assay
• Mechanism Description: The most common gyrase mutations in quinolone-resistant strains of B. anthracis are found at the conserved serine and glutamic acid residues (GyrAS85 and GyrAE89). In laboratory strains selected for resistance against ciprofloxacin and/or moxifloxacin (two widely prescribed quinolone antibacterials), approximately 80% of the isolates carried a GyrAS85L mutation (either alone or in combination with other gyrase/topoisomerase IV amino acid changes). The only other mutation reported to cause resistance without any other gyrase/topoisomerase IV changes was a GyrAE89K substitution.

Moxi-dione {3-amino-7-[(4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]-1-cyclopropyl-6-fluoro-8-methoxy-2,4(1H,3H)-quinazolinedione}

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Anthrax [1]

• Resistant Disease: Anthrax [ICD-11: 1B97.0]
• Resistant Drug: Moxi-dione {3-amino-7-[(4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]-1-cyclopropyl-6-fluoro-8-methoxy-2,4(1H,3H)-quinazolinedione}
• Molecule Alteration: Mutation; p.S85+p.S85F+p.E89K+p.E89A
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli strain; 562
• In Vitro Model: Bacillus anthracis strain; 1392
• Experiment for Molecule Alteration: DNA cleavage assay
• Mechanism Description: The most common gyrase mutations in quinolone-resistant strains of B. anthracis are found at the conserved serine and glutamic acid residues (GyrAS85 and GyrAE89). In laboratory strains selected for resistance against ciprofloxacin and/or moxifloxacin (two widely prescribed quinolone antibacterials), approximately 80% of the isolates carried a GyrAS85L mutation (either alone or in combination with other gyrase/topoisomerase IV amino acid changes). The only other mutation reported to cause resistance without any other gyrase/topoisomerase IV changes was a GyrAE89K substitution.

References

• Ref 1: Interactions between Quinolones and Bacillus anthracis Gyrase and the Basis of Drug Resistance .Biochemistry. 2017 Aug 15;56(32):4191-4200. doi: 10.1021/acs.biochem.7b00203. Epub 2017 Aug 1. 10.1021/acs.biochem.7b00203