Drug Information

Drug (ID: DG00256) and It's Reported Resistant Information

• Name: Chlortetracycline
• Synonyms: Aureomycin
• Indication:
  In total 1 Indication(s)
  Glanders [ICD-11: 1B92]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Bacillus infection [ICD-11: 1C4Y]; [2]
  Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (2 diseases)
  Bacterial infection [ICD-11: 1A00-1C4Z]; [1]
  Gram-negative bacterial infection [ICD-11: 1B74-1G40]; [3]
• Formula: C22H23ClN2O8
• IsoSMILES: C[C@@]1([C@H]2C[C@H]3[C@@H](C(=O)C(=C([C@]3(C(=O)C2=C(C4=C(C=CC(=C41)Cl)O)O)O)O)C(=O)N)N(C)C)O
• InChI: 1S/C22H23ClN2O8/c1-21(32)7-6-8-15(25(2)3)17(28)13(20(24)31)19(30)22(8,33)18(29)11(7)16(27)12-10(26)5-4-9(23)14(12)21/h4-5,7-8,15,26-27,30,32-33H,6H2,1-3H3,(H2,24,31)/t7-,8-,15-,21-,22-/m0/s1
• InChIKey: DHPRQBPJLMKORJ-XRNKAMNCSA-N
• PubChem CID: 54675777
• ChEBI ID: CHEBI:27644
• TTD Drug ID: D0R6RC
• DrugBank ID: DB09093

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

  IDUE: Irregularity in Drug Uptake and Drug Efflux

  UAPP: Unusual Activation of Pro-survival Pathway

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

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Tetracycline resistance protein Tet (TETW/N/W) [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(W/N/W) encodes mosaic ribosomal protection(since tetracyclines bind to the 30S ribosomal subunit to inhibit protein translation) and induces resistance.

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.

Gram-negative bacterial infection [ICD-11: 1B74-1G40]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: MipA/OmpV family protein (MIPA) [3]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Gram-negative bacterial infection [ICD-11: 1B74-1G40]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli k-12 BW25113; 679895
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: OM proteins, a unique OM component of Gram-negative bacteria, constitute a barrier against large hydrophilic and lipophilic molecules and therefore play an important role in stress responses to drugs, osmotic pressure and acids.MipA is a novel OM protein related to antibiotic resistance.

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: Outer membrane proteomics of kanamycin-resistant Escherichia coli identified MipA as a novel antibiotic resistance-related protein. FEMS Microbiol Lett. 2015 Jun;362(11):fnv074. doi: 10.1093/femsle/fnv074. Epub 2015 May 3.