Molecule Information

General Information of the Molecule (ID: Mol00938)

• Name: DNA topoisomerase 4 subunit B (PARE) ,Escherichia coli
• Synonyms: Topoisomerase IV subunit B; nfxD; b3030; JW2998
• Molecule Type: Protein
• Gene Name: parE
• Gene ID: 66673071
• Sequence:
  MTQTYNADAIEVLTGLEPVRRRPGMYTDTTRPNHLGQEVIDNSVDEALAGHAKRVDVILH
  ADQSLEVIDDGRGMPVDIHPEEGVPAVELILCRLHAGGKFSNKNYQFSGGLHGVGISVVN
  ALSKRVEVNVRRDGQVYNIAFENGEKVQDLQVVGTCGKRNTGTSVHFWPDETFFDSPRFS
  VSRLTHVLKAKAVLCPGVEITFKDEINNTEQRWCYQDGLNDYLAEAVNGLPTLPEKPFIG
  NFAGDTEAVDWALLWLPEGGELLTESYVNLIPTMQGGTHVNGLRQGLLDAMREFCEYRNI
  LPRGVKLSAEDIWDRCAYVLSVKMQDPQFAGQTKERLSSRQCAAFVSGVVKDAFILWLNQ
  NVQAAELLAEMAISSAQRRMRAAKKVVRKKLTSGPALPGKLADCTAQDLNRTELFLVEGD
  SAGGSAKQARDREYQAIMPLKGKILNTWEVSSDEVLASQEVHDISVAIGIDPDSDDLSQL
  RYGKICILADADSDGLHIATLLCALFVKHFRALVKHGHVYVALPPLYRIDLGKEVYYALT
  EEEKEGVLEQLKRKKGKPNVQRFKGLGEMNPMQLRETTLDPNTRRLVQLTIDDEDDQRTD
  AMMDMLLAKKRSEDRRNWLQEKGDMAEIEV
• Function: Topoisomerase IV is essential for chromosome segregation; it is the principal protein responsible for decatenating newly replicated chromosomes. It relaxes supercoiled DNA. MukB stimulates the relaxation activity of topoisomerase IV and also has a modest effect on decatenation.
• Uniprot ID: PARE_ECOLI

Kingdom: N.A.
Phylum: Proteobacteria
Class: Gammaproteobacteria
Order: Enterobacterales
Family: Enterobacteriaceae
Genus: Escherichia
Species: Escherichia coli

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) 4 drug(s) in total

Ciprofloxacin XR

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Escherichia coli infection [1]

• Resistant Disease: Escherichia coli infection [ICD-11: 1A03.0]
• Resistant Drug: Ciprofloxacin XR
• Molecule Alteration: Missense mutation; p.D476N
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli ECIS803; 562
• In Vitro Model: Escherichia coli ATCC 43869; 562
• Experiment for Molecule Alteration: PCR; DNA sequence assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Mutational substitutions in the quinolone target enzymes, namely DNA topoisomerase II (GyrA) and topoisomerase IV (ParC), are recognised to be the major mechanisms through which resistance develops.

Nalidixic acid

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Escherichia coli infection [1]

• Resistant Disease: Escherichia coli infection [ICD-11: 1A03.0]
• Resistant Drug: Nalidixic acid
• Molecule Alteration: Missense mutation; p.D476N
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli ECIS803; 562
• In Vitro Model: Escherichia coli ATCC 43869; 562
• Experiment for Molecule Alteration: PCR; DNA sequence assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Mutational substitutions in the quinolone target enzymes, namely DNA topoisomerase II (GyrA) and topoisomerase IV (ParC), are recognised to be the major mechanisms through which resistance develops.

Novobiocin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Staphylococcus aureus infection [2]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Novobiocin
• Molecule Alteration: Missense mutation; p.G78S
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus RN4220; 1280
• Experiment for Molecule Alteration: PCR amplification and DNA sequence assay
• Experiment for Drug Resistance: Twofold agar dilution method assay
• Mechanism Description: At first, successive point mutations specifically occurred in gyrB; next, a point mutation occurred in parE; finally, a point mutation occurred in gyrB again. The accumulation of mutations in both the gyrB and the parE genes is associated with high-level resistance to novobiocin.

Disease Class: Staphylococcus aureus infection [2]

• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Resistant Drug: Novobiocin
• Molecule Alteration: Missense mutation; p.R136G
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus RN4220; 1280
• Experiment for Molecule Alteration: PCR amplification and DNA sequence assay
• Experiment for Drug Resistance: Twofold agar dilution method assay
• Mechanism Description: At first, successive point mutations specifically occurred in gyrB; next, a point mutation occurred in parE; finally, a point mutation occurred in gyrB again. The accumulation of mutations in both the gyrB and the parE genes is associated with high-level resistance to novobiocin.

Ofloxacin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Escherichia coli infection [1]

• Resistant Disease: Escherichia coli infection [ICD-11: 1A03.0]
• Resistant Drug: Ofloxacin
• Molecule Alteration: Missense mutation; p.D476N
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli ECIS803; 562
• In Vitro Model: Escherichia coli ATCC 43869; 562
• Experiment for Molecule Alteration: PCR; DNA sequence assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Mutational substitutions in the quinolone target enzymes, namely DNA topoisomerase II (GyrA) and topoisomerase IV (ParC), are recognised to be the major mechanisms through which resistance develops.

References

• Ref 1: Characterisation of novel mutations involved in quinolone resistance in Escherichia coli isolated from imported shrimp. Int J Antimicrob Agents. 2015 May;45(5):471-6. doi: 10.1016/j.ijantimicag.2014.11.010. Epub 2015 Jan 13.
• Ref 2: Accumulation of mutations in both gyrB and parE genes is associated with high-level resistance to novobiocin in Staphylococcus aureus. Antimicrob Agents Chemother. 2005 Sep;49(9):3810-5. doi: 10.1128/AAC.49.9.3810-3815.2005.