Disease Information

General Information of the Disease (ID: DIS00155)

• Name: Anthrax
• ICD: ICD-11: 1B97

Type(s) of Resistant Mechanism of This Disease

  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)

Key Molecule: DNA gyrase subunit A (GYRA) [1]

• Resistant Disease: Anthrax [ICD-11: 1B97.0]
• Molecule Alteration: Mutation; p.S85+p.S85F+p.E89K+p.E89A
• Resistant Drug: Ciprofloxacin XR
• 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)

Key Molecule: DNA gyrase subunit A (GYRA) [1]

• Resistant Disease: Anthrax [ICD-11: 1B97.0]
• Molecule Alteration: Mutation; p.S85+p.S85F+p.E89K+p.E89A
• Resistant Drug: Moxifloxacin
• 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)

Key Molecule: DNA gyrase subunit A (GYRA) [1]

• Resistant Disease: Anthrax [ICD-11: 1B97.0]
• Molecule Alteration: Mutation; p.S85+p.S85F+p.E89K+p.E89A
• 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}
• 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)

Key Molecule: DNA gyrase subunit A (GYRA) [1]

• Resistant Disease: Anthrax [ICD-11: 1B97.0]
• Molecule Alteration: Mutation; p.S85+p.S85F+p.E89K+p.E89A
• 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}
• 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)

Key Molecule: DNA gyrase subunit A (GYRA) [1]

• Resistant Disease: Anthrax [ICD-11: 1B97.0]
• Molecule Alteration: Mutation; p.S85+p.S85F+p.E89K+p.E89A
• 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}
• 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)

Key Molecule: DNA gyrase subunit A (GYRA) [1]

• Resistant Disease: Anthrax [ICD-11: 1B97.0]
• Molecule Alteration: Mutation; p.S85+p.S85F+p.E89K+p.E89A
• Resistant Drug: 8-methoxy-cipro [1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-(1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid]
• 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)

Key Molecule: DNA gyrase subunit A (GYRA) [1]

• Resistant Disease: Anthrax [ICD-11: 1B97.0]
• Molecule Alteration: Mutation; p.S85+p.S85F+p.E89K+p.E89A
• Resistant Drug: 8-methyl-cipro [1-cyclopropyl-6-fluoro-1,4-dihydro-8-methyl-7-(1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid]
• 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)

Key Molecule: DNA gyrase subunit A (GYRA) [1]

• Resistant Disease: Anthrax [ICD-11: 1B97.0]
• Molecule Alteration: Mutation; p.S85+p.S85F+p.E89K+p.E89A
• 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}
• 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)

Key Molecule: DNA gyrase subunit A (GYRA) [1]

• Resistant Disease: Anthrax [ICD-11: 1B97.0]
• Molecule Alteration: Mutation; p.S85+p.S85F+p.E89K+p.E89A
• Resistant Drug: Cipro-dione [3-amino-7-(1-piperazinyl)-1-cyclopropyl-6-fluoro-2,4(1H,3H)-quinazolinedione]
• 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)

Key Molecule: DNA gyrase subunit A (GYRA) [1]

• Resistant Disease: Anthrax [ICD-11: 1B97.0]
• Molecule Alteration: Mutation; p.S85+p.S85F+p.E89K+p.E89A
• 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}
• 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