Molecule Information

General Information of the Molecule (ID: Mol00920)

• Name: DNA gyrase subunit A (GYRA) ,Burkholderia cepacia
• Synonyms: WS90_23820; WT26_08525
• Molecule Type: Protein
• Gene Name: gyrA
• Sequence:
  MDQFAKETLPTSLEEEMRRSYLDYAMSVIVGRALPDVRDGLKPVHRRVLFAMHELNNDWN
  RAYKKSARIVGDVIGKYHPHGDTAVYDTIVRMAQDFSLRYMLIDGQGNFGSIDGDNAAAM
  RYTEIRMAKIGHELLADIDKETVDFEPNYDGNEMQPSVLPSRIPNLLINGSSGIAVGMAT
  NIPPHNLNEVVDACQHLLGNPEATIDELIEIIPAPDFPTAGIIYGVAGVRDGYRTGRGRV
  VMRAATHFEEIDRGQRMAIIVDELPYQVNKRSLLERIAELVNEKKLEGISDIRDESDKSG
  MRVVIELKRGEVPEVVLNNLYKATQLQDTFGMNMVALVDGQPKLLNLKEILQCFLSHRRE
  VLTRRTIYELRKARERGHVLEGLAVALANIDEFIAIIKAAPTPPIAKAELMAKPWDSSLV
  REMLTRAESENAAAGGRSAYRPEGLNPAFGMQGDGLYRLSDTQAQEILQMRLQRLTGLEQ
  DKIIGEYREVMAQIADLLDILARPERITTMIGEELTSVKAEFGDARRSKIELNATELNTE
  DLITPQDMVVTMSHAGYVKSQPLSEYRAQKRGGRGKQATQMKEDDWIETLFIANTHDYIL
  CFSNRGRVYWVKVYEVPQGSRNSRGRPIVNMFPLQEGEKINVVLPVKEFSADKFIFMATS
  LGTVKKTPLEAFSRPMKKGIIAVGLDEGDYLIGASITDGAHDVMLFSDSGKAVRFDENDV
  RPMGREARGVRGMQLEDGQQVIAMLVAGSEEQTVLTATENGYGKRTPITEYTRHGRGTKG
  MIAIQTSERNGKVVAATLVDAEDQIMLITTAGVLIRTRVSEIREMGRATQGVTLISLDEG
  TKLSGLQQIAEAEEGDGEADEASDGEA
• 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: A0A103ZCJ7_BURCE

Kingdom: N.A.
Phylum: Proteobacteria
Class: Betaproteobacteria
Order: Burkholderiales
Family: Burkholderiaceae
Genus: Burkholderia
Species: Burkholderia cepacia

Type(s) of Resistant Mechanism of This Molecule

  ADTT: Aberration of the Drug's Therapeutic Target

  EADR: Epigenetic Alteration of DNA, RNA or Protein

Drug Resistance Data Categorized by Drug

Approved Drug(s) 7 drug(s) in total

Ciprofloxacin XR

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Bacterial infection [1], [2]

• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Resistant Drug: Ciprofloxacin XR
• Molecule Alteration: Missense mutation; p.T83I
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pseudomonas aeruginosa isolates; 287
• In Vitro Model: Pseudomonas aeruginosa ATCC10145; 287
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Etest assay
• Mechanism Description: The major mechanism of the resistance of this Pseudomonas aeruginosa to fluoroquinolones is the modification of type II topoisomerases (DNA gyrase and topoisomerase IV).

Disease Class: Bacterial infection [1], [2]

• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Resistant Drug: Ciprofloxacin XR
• Molecule Alteration: Missense mutation; p.H83R
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pseudomonas aeruginosa isolates; 287
• In Vitro Model: Pseudomonas aeruginosa ATCC10145; 287
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Etest assay
• Mechanism Description: The major mechanism of the resistance of this Pseudomonas aeruginosa to fluoroquinolones is the modification of type II topoisomerases (DNA gyrase and topoisomerase IV).

Disease Class: Gonococcal infection [3], [4]

• Resistant Disease: Gonococcal infection [ICD-11: 1A70.0]
• Resistant Drug: Ciprofloxacin XR
• Molecule Alteration: Missense mutation; p.S91F+p.D95G/D95A
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Neisseria gonorrhoeae isolates; 485
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Etest assay
• Mechanism Description: Fluoroquinolones block DNA replication by inhibiting the enzymes DNA gyrase (topoisomerase II) and topoisomerase IV. DNA gyrase catalyzes the untwisting of DNA molecules during DNA replication, and consists of two type A subunits and two type B subunits encoded by gyrA and gyrB genes. Topoisomerase IV consists of two type C subunits and two type E subunits encoded by parC and parE genes.GyrA S91F, D95G/D95A and ParC E91G amino acid substitutions mediate high fluoroquinolone resistance in the analyzed kenyan GC.

Disease Class: Typhoid fever [5]

• Resistant Disease: Typhoid fever [ICD-11: 1A07.0]
• Resistant Drug: Ciprofloxacin XR
• Molecule Alteration: Missense mutation; p.S83F
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Salmonella enterica subsp. enterica serovar Typhi isolates; 90370
• Experiment for Molecule Alteration: PCR-RFLP
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: The targets of fluoroquinolones are the two enzymes, DNA gyrase and topoisomerase IV, whose subunits are encoded respectively by gyrA and gyrB and the parC and parE genes.The alteration caused by single point mutations within the QRDR of the DNA gyrase subunit gyrA gene leads to quinolone resistance.

Disease Class: Gastroenteritis [5], [6]

• Resistant Disease: Gastroenteritis [ICD-11: 1A40.0]
• Resistant Drug: Ciprofloxacin XR
• Molecule Alteration: Missense mutation; p.S97P
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Salmonella enteritidis isolates; 149539
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Etest assay
• Mechanism Description: Quinolones target the bacterial DNA gyrase; this enzyme is a type II topoisomerase that is essential for bacterial DNA replication.This enzyme consists of 2A and 2B subunits encoded by gyrA and gyrB genes, respectively.

Disease Class: Gastroenteritis [5], [6]

• Resistant Disease: Gastroenteritis [ICD-11: 1A40.0]
• Resistant Drug: Ciprofloxacin XR
• Molecule Alteration: Missense mutation; p.S83F
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Salmonella enteritidis isolates; 149539
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Etest assay
• Mechanism Description: Quinolones target the bacterial DNA gyrase; this enzyme is a type II topoisomerase that is essential for bacterial DNA replication.This enzyme consists of 2A and 2B subunits encoded by gyrA and gyrB genes, respectively.

Disease Class: Gastroenteritis [5], [6]

• Resistant Disease: Gastroenteritis [ICD-11: 1A40.0]
• Resistant Drug: Ciprofloxacin XR
• Molecule Alteration: Missense mutation; p.D87Y
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Salmonella enteritidis isolates; 149539
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Etest assay
• Mechanism Description: Quinolones target the bacterial DNA gyrase; this enzyme is a type II topoisomerase that is essential for bacterial DNA replication.This enzyme consists of 2A and 2B subunits encoded by gyrA and gyrB genes, respectively.

Disease Class: Gastroenteritis [5], [6]

• Resistant Disease: Gastroenteritis [ICD-11: 1A40.0]
• Resistant Drug: Ciprofloxacin XR
• Molecule Alteration: Missense mutation; p.D87N
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Salmonella enteritidis isolates; 149539
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Etest assay
• Mechanism Description: Quinolones target the bacterial DNA gyrase; this enzyme is a type II topoisomerase that is essential for bacterial DNA replication.This enzyme consists of 2A and 2B subunits encoded by gyrA and gyrB genes, respectively.

Disease Class: Bacterial infection [7]

• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Resistant Drug: Ciprofloxacin XR
• Molecule Alteration: Missense mutation; p.S83L; p.S80L
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli ATCC 25922; 1322345
• In Vitro Model: Pseudomonas aeruginosa ATCC 27853; 287
• Experiment for Molecule Alteration: ERIC-PCR
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: Mutations that occur in gyrA and parC genes were detected by DNA sequence analysis in 16 resistant strains representing each clone and subtype.

Disease Class: Bartonella bacilliformis infection [8]

• Resistant Disease: Bartonella bacilliformis infection [ICD-11: 1C11.0]
• Resistant Drug: Ciprofloxacin XR
• Molecule Alteration: Missense mutation; p.D95N
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Bartonella bacilliformis kC583; 360095
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: The mutation of bartonella bacilliformis at asp-95 residue of gyrA QRDR resulted in the production of ciprofloxacin resistant strains.

Disease Class: Bartonella bacilliformis infection [8]

• Resistant Disease: Bartonella bacilliformis infection [ICD-11: 1C11.0]
• Resistant Drug: Ciprofloxacin XR
• Molecule Alteration: Missense mutation; p.D90G
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Bartonella bacilliformis kC583; 360095
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: The mutation of bartonella bacilliformis at asp-90 residue of gyrA QRDR resulted in the production of ciprofloxacin resistant strains.

Disease Class: Pneumocystis jirovecii infection [9]

• Resistant Disease: Pneumocystis jirovecii infection [ICD-11: CA40.6]
• Resistant Drug: Ciprofloxacin XR
• Molecule Alteration: Missense mutation; p.S843F (TCC-TTC)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae strain BM4203-BM4203-R; 1313
• In Vitro Model: Streptococcus pneumoniae strain BM4204-BM4204-R; 1313
• Experiment for Molecule Alteration: Sequence analysis
• Experiment for Drug Resistance: Agar dilution assay
• Mechanism Description: An additional mutant obtained in vitro, BM4205-R3, displayed a higher level of fluoroquinolone resistance and had a mutation in gyrA leading to a Ser-84-Phe change.

Levofloxacin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Bacterial infection [7]

• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Resistant Drug: Levofloxacin
• Molecule Alteration: Missense mutation; p.S83L; p.S80L
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli ATCC 25922; 1322345
• In Vitro Model: Pseudomonas aeruginosa ATCC 27853; 287
• Experiment for Molecule Alteration: ERIC-PCR
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: Mutations that occur in gyrA and parC genes were detected by DNA sequence analysis in 16 resistant strains representing each clone and subtype.

Disease Class: Bacterial infection [10], [11]

• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Resistant Drug: Levofloxacin
• Molecule Alteration: Missense mutation; p.T83I
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Burkholderia cepacia isolates; 292
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Among six levofloxacin-resistant isolates, five had single-base substitutions in the gyrA gene.

Disease Class: Bacterial infection [10], [11]

• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Resistant Drug: Levofloxacin
• Molecule Alteration: Missense mutation; p.D87H
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Burkholderia cepacia isolates; 292
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Among six levofloxacin-resistant isolates, five had single-base substitutions in the gyrA gene.

Disease Class: Bacterial infection [10], [11]

• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Resistant Drug: Levofloxacin
• Molecule Alteration: Missense mutation; p.G81D
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Burkholderia cepacia isolates; 292
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Among six levofloxacin-resistant isolates, five had single-base substitutions in the gyrA gene.

Nalidixic acid

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Shigella intestinal infection [12]

• Resistant Disease: Shigella intestinal infection [ICD-11: 1A02.0]
• Resistant Drug: Nalidixic acid
• Molecule Alteration: Missense mutation; p.N57K
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli ATCC 25922; 1322345
• In Vitro Model: Escherichia coli ATCC 35218; 562
• In Vitro Model: Shigella flexneri isolates; 623
• Experiment for Molecule Alteration: PCR; DNA sequence assay
• Experiment for Drug Resistance: Disk diffusion test assay
• Mechanism Description: Mutations Asn57Lys and His80Pro in gyrA and Ala85Thr, Asp111His and Ser129Pro in parC. induce fluoroquinolone resistance with a significantly high mutation rate of the gyrA and parC genes in S. flexneri.

Disease Class: Shigella intestinal infection [12]

• Resistant Disease: Shigella intestinal infection [ICD-11: 1A02.0]
• Resistant Drug: Nalidixic acid
• Molecule Alteration: Missense mutation; p.H80P
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli ATCC 25922; 1322345
• In Vitro Model: Escherichia coli ATCC 35218; 562
• In Vitro Model: Shigella flexneri isolates; 623
• Experiment for Molecule Alteration: PCR; DNA sequence assay
• Experiment for Drug Resistance: Disk diffusion test assay
• Mechanism Description: Mutations Asn57Lys and His80Pro in gyrA and Ala85Thr, Asp111His and Ser129Pro in parC. induce fluoroquinolone resistance with a significantly high mutation rate of the gyrA and parC genes in S. flexneri.

Disease Class: Gastroenteritis [5], [6]

• Resistant Disease: Gastroenteritis [ICD-11: 1A40.0]
• Resistant Drug: Nalidixic acid
• Molecule Alteration: Missense mutation; p.S97P
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Salmonella enteritidis isolates; 149539
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Etest assay
• Mechanism Description: Quinolones target the bacterial DNA gyrase; this enzyme is a type II topoisomerase that is essential for bacterial DNA replication.This enzyme consists of 2A and 2B subunits encoded by gyrA and gyrB genes, respectively.

Disease Class: Gastroenteritis [5], [6]

• Resistant Disease: Gastroenteritis [ICD-11: 1A40.0]
• Resistant Drug: Nalidixic acid
• Molecule Alteration: Missense mutation; p.S83F
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Salmonella enteritidis isolates; 149539
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Etest assay
• Mechanism Description: Quinolones target the bacterial DNA gyrase; this enzyme is a type II topoisomerase that is essential for bacterial DNA replication.This enzyme consists of 2A and 2B subunits encoded by gyrA and gyrB genes, respectively.

Disease Class: Gastroenteritis [5], [6]

• Resistant Disease: Gastroenteritis [ICD-11: 1A40.0]
• Resistant Drug: Nalidixic acid
• Molecule Alteration: Missense mutation; p.D87Y
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Salmonella enteritidis isolates; 149539
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Etest assay
• Mechanism Description: Quinolones target the bacterial DNA gyrase; this enzyme is a type II topoisomerase that is essential for bacterial DNA replication.This enzyme consists of 2A and 2B subunits encoded by gyrA and gyrB genes, respectively.

Disease Class: Gastroenteritis [5], [6]

• Resistant Disease: Gastroenteritis [ICD-11: 1A40.0]
• Resistant Drug: Nalidixic acid
• Molecule Alteration: Missense mutation; p.D87N
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Salmonella enteritidis isolates; 149539
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Etest assay
• Mechanism Description: Quinolones target the bacterial DNA gyrase; this enzyme is a type II topoisomerase that is essential for bacterial DNA replication.This enzyme consists of 2A and 2B subunits encoded by gyrA and gyrB genes, respectively.

Norfloxacin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Shigella intestinal infection [12]

• Resistant Disease: Shigella intestinal infection [ICD-11: 1A02.0]
• Resistant Drug: Norfloxacin
• Molecule Alteration: Missense mutation; p.N57K
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli ATCC 25922; 1322345
• In Vitro Model: Escherichia coli ATCC 35218; 562
• In Vitro Model: Shigella flexneri isolates; 623
• Experiment for Molecule Alteration: PCR; DNA sequence assay
• Experiment for Drug Resistance: Disk diffusion test assay
• Mechanism Description: Mutations Asn57Lys and His80Pro in gyrA and Ala85Thr, Asp111His and Ser129Pro in parC. induce fluoroquinolone resistance with a significantly high mutation rate of the gyrA and parC genes in S. flexneri.

Disease Class: Shigella intestinal infection [12]

• Resistant Disease: Shigella intestinal infection [ICD-11: 1A02.0]
• Resistant Drug: Norfloxacin
• Molecule Alteration: Missense mutation; p.H80P
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli ATCC 25922; 1322345
• In Vitro Model: Escherichia coli ATCC 35218; 562
• In Vitro Model: Shigella flexneri isolates; 623
• Experiment for Molecule Alteration: PCR; DNA sequence assay
• Experiment for Drug Resistance: Disk diffusion test assay
• Mechanism Description: Mutations Asn57Lys and His80Pro in gyrA and Ala85Thr, Asp111His and Ser129Pro in parC. induce fluoroquinolone resistance with a significantly high mutation rate of the gyrA and parC genes in S. flexneri.

Ofloxacin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Bacterial infection [1], [2]

• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Resistant Drug: Ofloxacin
• Molecule Alteration: Missense mutation; p.T83I
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pseudomonas aeruginosa isolates; 287
• In Vitro Model: Pseudomonas aeruginosa ATCC10145; 287
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Etest assay
• Mechanism Description: The major mechanism of the resistance of this Pseudomonas aeruginosa to fluoroquinolones is the modification of type II topoisomerases (DNA gyrase and topoisomerase IV).

Disease Class: Bacterial infection [1], [2]

• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Resistant Drug: Ofloxacin
• Molecule Alteration: Missense mutation; p.H83R
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pseudomonas aeruginosa isolates; 287
• In Vitro Model: Pseudomonas aeruginosa ATCC10145; 287
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Etest assay
• Mechanism Description: The major mechanism of the resistance of this Pseudomonas aeruginosa to fluoroquinolones is the modification of type II topoisomerases (DNA gyrase and topoisomerase IV).

Pefloxacin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Pneumocystis jirovecii infection [9]

• Resistant Disease: Pneumocystis jirovecii infection [ICD-11: CA40.6]
• Resistant Drug: Pefloxacin
• Molecule Alteration: Missense mutation; p.S843F (TCC-TTC)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae strain BM4203-BM4203-R; 1313
• In Vitro Model: Streptococcus pneumoniae strain BM4204-BM4204-R; 1313
• Experiment for Molecule Alteration: Sequence analysis
• Experiment for Drug Resistance: Agar dilution assay
• Mechanism Description: An additional mutant obtained in vitro, BM4205-R3, displayed a higher level of fluoroquinolone resistance and had a mutation in gyrA leading to a Ser-84-Phe change.

Sparfloxacin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Pneumocystis jirovecii infection [9]

• Resistant Disease: Pneumocystis jirovecii infection [ICD-11: CA40.6]
• Resistant Drug: Sparfloxacin
• Molecule Alteration: Missense mutation; p.S843F (TCC-TTC)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae strain BM4203-BM4203-R; 1313
• In Vitro Model: Streptococcus pneumoniae strain BM4204-BM4204-R; 1313
• Experiment for Molecule Alteration: Sequence analysis
• Experiment for Drug Resistance: Agar dilution assay
• Mechanism Description: An additional mutant obtained in vitro, BM4205-R3, displayed a higher level of fluoroquinolone resistance and had a mutation in gyrA leading to a Ser-84-Phe change.

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

PD131628

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Pneumocystis jirovecii infection [9]

• Resistant Disease: Pneumocystis jirovecii infection [ICD-11: CA40.6]
• Resistant Drug: PD131628
• Molecule Alteration: Missense mutation; p.S843F (TCC-TTC)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae strain BM4203-BM4203-R; 1313
• In Vitro Model: Streptococcus pneumoniae strain BM4204-BM4204-R; 1313
• Experiment for Molecule Alteration: Sequence analysis
• Experiment for Drug Resistance: Agar dilution assay
• Mechanism Description: An additional mutant obtained in vitro, BM4205-R3, displayed a higher level of fluoroquinolone resistance and had a mutation in gyrA leading to a Ser-84-Phe change.

References

• Ref 1: gyrA and parC mutations in quinolone-resistant clinical isolates of Pseudomonas aeruginosa from Nini Hospital in north Lebanon. J Infect Chemother. 2013 Feb;19(1):77-81. doi: 10.1007/s10156-012-0455-y. Epub 2012 Jul 21.
• Ref 2: DNA gyrase gyrA mutations in quinolone-resistant clinical isolates of Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1995 Sep;39(9):1970-2. doi: 10.1128/AAC.39.9.1970.
• Ref 3: Molecular epidemiology of drug-resistant Neisseria gonorrhoeae in Russia (Current Status, 2015). BMC Infect Dis. 2016 Aug 9;16:389. doi: 10.1186/s12879-016-1688-7.
• Ref 4: gyrA and parC mutations in fluoroquinolone-resistant Neisseria gonorrhoeae isolates from Kenya. BMC Microbiol. 2019 Apr 8;19(1):76. doi: 10.1186/s12866-019-1439-1.
• Ref 5: GyrA ser83 and ParC trp106 Mutations in Salmonella enterica Serovar Typhi Isolated from Typhoid Fever Patients in Tertiary Care Hospital. J Clin Diagn Res. 2016 Jul;10(7):DC14-8. doi: 10.7860/JCDR/2016/17677.8153. Epub 2016 Jul 1.
• Ref 6: Prevalence of gyrA Mutations in Nalidixic Acid-Resistant Strains of Salmonella Enteritidis Isolated from Humans, Food, Chickens, and the Farm Environment in Brazil. Microb Drug Resist. 2017 Jun;23(4):421-428. doi: 10.1089/mdr.2016.0024. Epub 2016 Aug 25.
• Ref 7: [Investigation of fluoroquinolone resistance mechanisms in clinical Acinetobacter baumannii isolates]. Mikrobiyol Bul. 2016 Apr;50(2):278-86. doi: 10.5578/mb.24126.
• Ref 8: gyrA mutations in ciprofloxacin-resistant Bartonella bacilliformis strains obtained in vitro. Antimicrob Agents Chemother. 2003 Jan;47(1):383-6. doi: 10.1128/AAC.47.1.383-386.2003.
• Ref 9: Contribution of mutations in gyrA and parC genes to fluoroquinolone resistance of mutants of Streptococcus pneumoniae obtained in vivo and in vitro. Antimicrob Agents Chemother. 1996 Nov;40(11):2505-10. doi: 10.1128/AAC.40.11.2505.
• Ref 10: The contribution of antibiotic resistance mechanisms in clinical Burkholderia cepacia complex isolates: an emphasis on efflux pump activity. PLoS One. 2014 Aug 25;9(8):e104986. doi: 10.1371/journal.pone.0104986. eCollection 2014.
• Ref 11: Complete genome sequences for 59 burkholderia isolates, both pathogenic and near neighbor. Genome Announc. 2015 Apr 30;3(2):e00159-15. doi: 10.1128/genomeA.00159-15.
• Ref 12: Novel mutations in quinolone resistance-determining regions of gyrA, gyrB, parC and parE in Shigella flexneri clinical isolates from eastern Chinese populations between 2001 and 2011. Eur J Clin Microbiol Infect Dis. 2016 Dec;35(12):2037-2045. doi: 10.1007/s10096-016-2761-2. Epub 2016 Sep 12.