Drug Information

Drug (ID: DG00201) and It's Reported Resistant Information

• Name: Oxytetracycline
• Synonyms: Adamycin; Biostat; Dabicycline; Dalimycin; Fanterrin; Geomycin; Geotilin; Hydroxytetracycline; Imperacin; Lenocycline; Macocyn; OTC; Oksisyklin; Ossitetraciclina; Oxacycline; Oxitetraciclina; Oxitetracyclin; Oxitetracycline; Oxitetracyclinum; Oxymycin; Oxymykoin; Oxypam; Oxyterracin; Oxyterracine; Oxyterracyne; Oxytetracid; Oxytetracyclin; Oxytetracyclinum; Proteroxyna; Riomitsin; Ryomycin; Solkaciclina; Tarocyn; Tarosin; Teravit; Terrafungine; Terramitsin; Terramycin; Tetran; Unimycin; Ursocyclin; Ursocycline; Vendarcin; Biostat PA; Ossitetraciclina [DCIT]; Oxytetracycline HCl; Oxytetracycline [INN]; Oxytetracycline amphoteric; Oxytetracycline anhydrous; Oxytetracycline calcium; Terramycin im; Antibiotic TM 25; LA 200; Liquamycin LA 200; Mycoshield TMQTHC 20; Pennox 200; TM 5; Terramycin Q50; Geomycin (Streptomyces vimosus); OTC (antibiotic); Oxitetraciclina [INN-Spanish]; Oxytetracycline (anhydrous); Oxytetracycline (internal use); Oxytetracyclinum [INN-Latin]; Terramycin, Liquamycin, Oxytetracycline; (2E,4S,4aR,5S,5aR,6S,12aS)-2-[amino(hydroxy)methylidene]-4-(dimethylamino)-5,6,10,11,12a-pentahydroxy-6-methyl-4,4a,5,5a-tetrahydrotetracene-1,3,12-trione; (2E,4S,6S,12aS)-2-[amino(hydroxy)methylidene]-4-(dimethylamino)-5,6,10,11,12a-pentahydroxy-6-methyl-4,4a,5,5a-tetrahydrotetracene-1,3,12-trione; (2Z)-2-[amino(hydroxy)methylidene]-4-(dimethylamino)-5,6,10,11,12a-pentahydroxy-6-methyl-4,4a,5,5a-tetrahydrotetracene-1,3,12-trione; (2Z,4S,4aR,5S,5aR,6S,12aS)-2-[amino(hydroxy)methylidene]-4-(dimethylamino)-5,6,10,11,12a-pentahydroxy-6-methyl-4,4a,5,5a-tetrahydrotetracene-1,3,12-trione; (4S,4aR,5S,5aR,6S,12aS)-4-(dimethylamino)-3,5,6,10,12,12a-hexahydroxy-6-methyl-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide; 5-Hydroxytetracycline
• Indication:
  In total 1 Indication(s)
  Bacterial infection [ICD-11: 1A00-1C4Z]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (2 diseases)
  Bacillus infection [ICD-11: 1C4Y]; [2]
  Bacterial infection [ICD-11: 1A00-1C4Z]; [3]
  Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (1 diseases)
  Bacterial infection [ICD-11: 1A00-1C4Z]; [1]
• Target: Staphylococcus 30S ribosomal subunit (Stap-coc pbp2); F4NA87_STAAU; [1]
• Formula: C22H24N2O9
• IsoSMILES: C[C@@]1([C@H]2[C@@H]([C@H]3[C@@H](C(=O)C(=C([C@]3(C(=O)C2=C(C4=C1C=CC=C4O)O)O)O)C(=O)N)N(C)C)O)O
• InChI: 1S/C22H24N2O9/c1-21(32)7-5-4-6-8(25)9(7)15(26)10-12(21)17(28)13-14(24(2)3)16(27)11(20(23)31)19(30)22(13,33)18(10)29/h4-6,12-14,17,25-26,28,30,32-33H,1-3H3,(H2,23,31)/t12-,13-,14+,17+,21-,22+/m1/s1
• InChIKey: OWFJMIVZYSDULZ-PXOLEDIWSA-N
• PubChem CID: 54675779
• ChEBI ID: CHEBI:27701
• TTD Drug ID: D0J2NK
• INTEDE ID: DR2697
• DrugBank ID: DB00595

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

  IDUE: Irregularity in Drug Uptake and Drug Efflux

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-01: Infectious/parasitic diseases

Bacterial infection [ICD-11: 1A00-1C4Z]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Tetracycline resistance protein tet(59) (TET59) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli EPI-300; 562
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Tet(59) is preceded by a homolog of the tetracycline repressor tetR typically found upstream of tet genes encoding efflux pumps and include the two palindromic operator sequences present in all regulatory regions of the tet(A)-tet(R) family (33), suggesting that tet(59) probably belongs to the efflux pump family.

Key Molecule: Putative ABC transporter ATP-binding component (OTRC) [4]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli BL21 (DE3); 469008
• In Vitro Model: Escherichia coli; 668369
• In Vitro Model: Escherichia coli ET12567 (pUZ8002); 562
• In Vitro Model: Streptomyces rimosus M4018; 1927
• In Vitro Model: Streptomyces rimosus SR16; 1927
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: OtrC is a multidrug resistance protein based on an ATP hydrolysis-dependent active efflux mechanism.OtrC is a multidrug resistance protein based on an ATP hydrolysis-dependent active efflux mechanism.

Key Molecule: Tetracycline resistance protein class A (TETA) [3]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Corynebacterium striatum infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Corynebacterium glutamicum strain ATCC 13032; 196627
• In Vitro Model: Corynebacterium striatum strain M82B; 43770
• In Vitro Model: Escherichia coli strain DH5alphaMCR; 668369
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Macrodilution broth method assay
• Mechanism Description: The large multiresistance plasmid pTP10 was initially identified in the clinical isolate C. striatum M82B. This 51-kb R-plasmid was shown to carry the determinants for resistance to the antibiotics chloramphenicol, erythomycin, kanamycin, and tetracycline by ethidium bromide-based curing experiments. The tetracycline and oxacillin resistance region is part of a DNA segment structurally similar to the chromosome of the human pathogen Mycobacterium tuberculosis. A resistance assay in C. glutamicum demonstrated that the tetAB gene pair of pTP10 is necessary to confer resistance to the antibiotics tetracycline and oxytetracycline.

Key Molecule: Tetracycline resistance protein class A (TETA) [3]

• Molecule Alteration: Expression; Acquired
• Resistant Disease: Corynebacterium glutamicum infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Corynebacterium glutamicum strain ATCC 13032; 196627
• In Vitro Model: Corynebacterium striatum strain M82B; 43770
• In Vitro Model: Escherichia coli strain DH5alphaMCR; 668369
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Macrodilution broth method assay
• Mechanism Description: The large multiresistance plasmid pTP10 was initially identified in the clinical isolate C. striatum M82B. This 51-kb R-plasmid was shown to carry the determinants for resistance to the antibiotics chloramphenicol, erythomycin, kanamycin, and tetracycline by ethidium bromide-based curing experiments. Both resistance genes are located on mobile DNA elements that are capable of transposition into the chromosome of the non-pathogenic soil bacteriumC. glutamicum. A resistance assay in C. glutamicum demonstrated that the tetAB gene pair of pTP10 is necessary to confer resistance to the antibiotics tetracycline and oxytetracycline.

Bacillus infection [ICD-11: 1C4Y]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Tetracycline resistance protein TetQ (TETQ) [2]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Bacteroides spp infection [ICD-11: 1C4Y.9]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli DH5alpha; 668369
• Experiment for Molecule Alteration: PCR; Dot blot and Southern blot analysis
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: Tet36 is a new class of ribosome protection type tetracycline resistance protein and lead to drug resistance.

References

• Ref 1: Diversity of the Tetracycline Mobilome within a Chinese Pig Manure Sample. Appl Environ Microbiol. 2016 Oct 14;82(21):6454-6462. doi: 10.1128/AEM.01754-16. Print 2016 Nov 1.
• Ref 2: Identification of a new ribosomal protection type of tetracycline resistance gene, tet(36), from swine manure pits. Appl Environ Microbiol. 2003 Jul;69(7):4151-8. doi: 10.1128/AEM.69.7.4151-4158.2003.
• Ref 3: The 51,409-bp R-plasmid pTP10 from the multiresistant clinical isolate Corynebacterium striatum M82B is composed of DNA segments initially identified in soil bacteria and in plant, animal, and human pathogens. Mol Gen Genet. 2000 Feb;263(1):1-11. doi: 10.1007/pl00008668.
• Ref 4: Molecular cloning and functional characterization of an ATP-binding cassette transporter OtrC from Streptomyces rimosus. BMC Biotechnol. 2012 Aug 20;12:52. doi: 10.1186/1472-6750-12-52.