Disease Information

General Information of the Disease (ID: DIS00016)

• Name: Nongonococcal urethritis
• ICD: ICD-11: 1A81

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) 1 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], [2]

• Resistant Disease: Ureaplasma parvum infection [ICD-11: 1A81.1]
• Molecule Alteration: Missense mutation; p.S83L
• Resistant Drug: Ciprofloxacin XR
• 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.

Key Molecule: DNA gyrase subunit A (GYRA) [1], [2]

• Resistant Disease: Ureaplasma urealyticum infection [ICD-11: 1A81.2]
• Molecule Alteration: Missense mutation; p.S83L
• Resistant Drug: Ciprofloxacin XR
• 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.

Key Molecule: DNA topoisomerase 4 subunit A (PARC) [1], [2]

• Resistant Disease: Nongonococcal urethritis [ICD-11: 1A81.3]
• Molecule Alteration: Missense mutation; p.S83W
• Resistant Drug: Ciprofloxacin XR
• 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
• In Vitro Model: Ureaplasma parvum isolates; 38504
• 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.

Key Molecule: DNA topoisomerase 4 subunit A (PARC) [1], [2]

• Resistant Disease: Nongonococcal urethritis [ICD-11: 1A81.3]
• Molecule Alteration: Missense mutation; p.S83P
• Resistant Drug: Ciprofloxacin XR
• 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
• In Vitro Model: Ureaplasma parvum isolates; 38504
• 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.

Key Molecule: DNA topoisomerase 4 subunit A (PARC) [1], [2]

• Resistant Disease: Nongonococcal urethritis [ICD-11: 1A81.3]
• Molecule Alteration: Missense mutation; ParC p.S83L+GyrB p.P462S
• Resistant Drug: Ciprofloxacin XR
• 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
• In Vitro Model: Ureaplasma parvum isolates; 38504
• 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.