Drug Information

Drug (ID: DG00117) and It's Reported Resistant Information

• Name: Minocycline
• Synonyms: Borymycin; MINO; MIY; Minociclina; Minociclinum; Minocin; Minocline; Minocyclin; Minocyclinum; Minocycline Monohydrochloride; CL 59806; Lactoferrin B & Minocycline; Lactoferrin H & Minocycline; Minociclina [INN-Spanish]; Minocin (Hydrochloride); Minocin (TN); Minocyclinum [INN-Latin]; Vectrin (Hydrochloride); CRL-1605 & Minocycline; Minocycline (USAN/INN); Minocycline [USAN:BAN:INN]; (2Z,4S,4aS,5aR,12aS)-2-[amino(hydroxy)methylidene]-4,7-bis(dimethylamino)-10,11,12a-trihydroxy-4a,5,5a,6-tetrahydro-4H-tetracene-1,3,12-trione; (4S,4AS,5AR,12AS)-4,7-BIS(DIMETHYLAMINO)-3,10,12,12A-TETRAHYDROXY-1,11-DIOXO-1,4,4A,5,5A,6,11,12A-OCTAHYDROTETRACENE-2-CARBOXAMIDE; 4,7-Bis(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide; 7-Dimethylamino-6-demethyl-6-deoxytetracycline
• Indication:
  In total 2 Indication(s)
  Bacterial infection [ICD-11: 1A00-1C4Z]; Approved; [1]
  Rosacea [ICD-11: ED90]; Phase 2; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (3 diseases)
  Bacillus infection [ICD-11: 1C4Y]; [2]
  Bacterial infection [ICD-11: 1A00-1C4Z]; [3], [4]
  Helicobacter pylori infection [ICD-11: DA60]; [5]
  Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (2 diseases)
  Bacterial infection [ICD-11: 1A00-1C4Z]; [1]
  Campylobacteriosis [ICD-11: 1C40]; [6]
• Target: Staphylococcus 30S ribosomal subunit (Stap-coc pbp2); F4NA87_STAAU; [1]
• Formula: C23H27N3O7
• IsoSMILES: CN(C)[C@H]1[C@@H]2C[C@@H]3CC4=C(C=CC(=C4C(=C3C(=O)[C@@]2(C(=C(C1=O)C(=O)N)O)O)O)O)N(C)C
• InChI: 1S/C23H27N3O7/c1-25(2)12-5-6-13(27)15-10(12)7-9-8-11-17(26(3)4)19(29)16(22(24)32)21(31)23(11,33)20(30)14(9)18(15)28/h5-6,9,11,17,27-28,31,33H,7-8H2,1-4H3,(H2,24,32)/t9-,11-,17-,23-/m0/s1
• InChIKey: FFTVPQUHLQBXQZ-KVUCHLLUSA-N
• PubChem CID: 54675783
• ChEBI ID: CHEBI:50694
• TTD Drug ID: D08LTU
• DrugBank ID: DB01017

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

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.

Key Molecule: Protein TetT (TETT) [7]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Streptococcus pyogenes infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli strain TG1; 562
• In Vitro Model: Streptococcus agalactiae strain B130; 1311
• In Vitro Model: Streptococcus anginosus strain MG16; 1328
• In Vitro Model: Streptococcus anginosus strain MG23; 1328
• In Vitro Model: Streptococcus anginosus strain MG32; 1328
• In Vitro Model: Streptococcus bovis strain D135; 1335
• In Vitro Model: Streptococcus bovis strain D295; 1335
• In Vitro Model: Streptococcus equisimilis strain C94; 119602
• In Vitro Model: Streptococcus equisimilis strain C95; 119602
• In Vitro Model: Streptococcus equisimilis strain C96; 119602
• In Vitro Model: Streptococcus pyogenes strain A498; 1314
• In Vitro Model: Streptococcus sp. strain G59; 1306
• Experiment for Molecule Alteration: PCR
• Mechanism Description: The gene tet(T) was isolated from Streptococcus pyogenes A498, and the nucleotide sequence that was necessary and sufficient for the expression of tetracycline resistance in Escherichia coli was determined. The deduced Tet(T) protein consists of 651 amino acids. A phylogenetic analysis revealed that Tet T represents a novel branching order among the Tet determinants so far described.

Key Molecule: Tetracycline resistance protein TetS (TETS) [3], [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: Enterococcus faecalis JH2-2; 1351
• In Vitro Model: Enterococcus spp. Isolates; 35783
• In Vitro Model: Streptococcus milleri isolates; 33040
• In Vitro Model: Streptococcus sanguis isolates; 1305
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: TetS confers tetracycline and minocycline resistance by ribosomal protection.

Campylobacteriosis [ICD-11: 1C40]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Ribosomal tetracycline resistance protein tet(44) (TET44) [6]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Campylobacter fetus infection [ICD-11: 1C40.0]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli S17-1 Lambdapir; 1227813
• Experiment for Molecule Alteration: Illumina/Solexa sequencing assay
• Experiment for Drug Resistance: Broth microdilution assay
• Mechanism Description: The 640-amino-acid tetracycline resistance determinant, Tet 44, belongs to a class of proteins that confers resistance to tetracycline and minocycline by ribosomal protection.

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: Presence of the Listeria tetracycline resistance gene tet(S) in Enterococcus faecalis. Antimicrob Agents Chemother. 1994 Oct;38(10):2330-5. doi: 10.1128/AAC.38.10.2330.
• Ref 4: Characterization of a new class of tetracycline-resistance gene tet(S) in Listeria monocytogenes BM4210. Gene. 1993 Sep 6;131(1):27-34. doi: 10.1016/0378-1119(93)90665-p.
• Ref 5: Helicobacter pylori infection and antibiotic resistance - from biology to clinical implicationsNat Rev Gastroenterol Hepatol. 2021 Sep;18(9):613-629. doi: 10.1038/s41575-021-00449-x. Epub 2021 May 17.
• Ref 6: Two novel antibiotic resistance genes, tet(44) and ant(6)-Ib, are located within a transferable pathogenicity island in Campylobacter fetus subsp. fetus. Antimicrob Agents Chemother. 2010 Jul;54(7):3052-5. doi: 10.1128/AAC.00304-10. Epub 2010 May 17.
• Ref 7: New tetracycline resistance determinants coding for ribosomal protection in streptococci and nucleotide sequence of tet(T) isolated from Streptococcus pyogenes A498. Antimicrob Agents Chemother. 1997 Jan;41(1):112-6. doi: 10.1128/AAC.41.1.112.