Drug Information

Drug (ID: DG00187) and It's Reported Resistant Information

• Name: Tigecycline
• Synonyms: Tigilcycline; Tygacil; Tigecycline [USAN]; GAR 936; GAR-936; TBG-MINO; Tygacil (TN); Tygacil(TM); GAR-936,Tigecycline; Tigecycline (JAN/USAN); WAY-GAR-936; Tygacil, GAR-936, WAY-GAR-936, TBG-MINO, Tigecycline; N-[(5aR,6aS,7S,9Z,10aS)-9-[amino(hydroxy)methylidene]-4,7-bis(dimethylamino)-1,10a,12-trihydroxy-8,10,11-trioxo-5a,6,6a,7-tetrahydro-5H-tetracen-2-yl]-2-(tert-butylamino)acetamide; (4S,12aS)-4,7-Bis(dimethylamino)-9-{2-[(tert-butyl)amino]acetylamino}-3,10,12,12a-tetrahydroxy-1,11-dioxo-4,5,6,12a,4a,5a-hexahydronaphthacene-2-carboxamide; (4S,4aS,5aR,12aS)-9-(2-(tert-butylamino)acetamido)-4,7-bis(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide; (4S,4aS,5aR,12aS)-9-[(N-tert-butylglycyl)amino]-4,7-bis(dimethylamino)-3,10,12,12a-tetrahydroxy-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide; 9-t-Butylglycylamido minocycline
• Indication:
  In total 1 Indication(s)
  Skin and skin-structure infection [ICD-11: 1F28-1G0Z]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (2 diseases)
  Bacterial infection [ICD-11: 1A00-1C4Z]; [2]
  Lower respiratory tract infection [ICD-11: CA4Z]; [3]
• Target: Staphylococcus 30S ribosomal subunit (Stap-coc pbp2); F4NA87_STAAU; [1]
• Formula: C29H39N5O8
• IsoSMILES: CC(C)(C)NCC(=O)NC1=CC(=C2C[C@H]3C[C@H]4[C@@H](C(=O)C(=C([C@]4(C(=O)C3=C(C2=C1O)O)O)O)C(=O)N)N(C)C)N(C)C
• InChI: 1S/C29H39N5O8/c1-28(2,3)31-11-17(35)32-15-10-16(33(4)5)13-8-12-9-14-21(34(6)7)24(38)20(27(30)41)26(40)29(14,42)25(39)18(12)23(37)19(13)22(15)36/h10,12,14,21,31,36-37,40,42H,8-9,11H2,1-7H3,(H2,30,41)(H,32,35)/t12-,14-,21-,29-/m0/s1
• InChIKey: SOVUOXKZCCAWOJ-HJYUBDRYSA-N
• PubChem CID: 54686904
• ChEBI ID: CHEBI:149836
• TTD Drug ID: D0G4OD
• DrugBank ID: DB00560

Type(s) of Resistant Mechanism of This Drug

  DISM: Drug Inactivation by Structure Modification

  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

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Flavin-dependent monooxygenase (TETX4) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Acinetobacter specie infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Acinetobacter baumannii 34AB; 509173
• In Vitro Model: Escherichia coli 47EC; 562
• In Vivo Model: ICR female mice model; Mus musculus
• Experiment for Molecule Alteration: Genome extraction and sequencing assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: Two unique mobile tigecycline-resistance genes,Tet(X3) and Tet(X4), inactivate all tetracyclines, including tigecycline and the newly FDA-approved eravacycline and omadacycline.

Key Molecule: Flavin-dependent monooxygenase (TETX4) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Enterobacteriaceae infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Acinetobacter baumannii 34AB; 509173
• In Vitro Model: Escherichia coli 47EC; 562
• In Vivo Model: ICR female mice model; Mus musculus
• Experiment for Molecule Alteration: Genome extraction and sequencing assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: Two unique mobile tigecycline-resistance genes,Tet(X3) and Tet(X4), inactivate all tetracyclines, including tigecycline and the newly FDA-approved eravacycline and omadacycline.

Key Molecule: Flavin-dependent monooxygenase (TETX3) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Acinetobacter specie infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Acinetobacter baumannii 34AB; 509173
• In Vitro Model: Escherichia coli 47EC; 562
• In Vivo Model: ICR female mice model; Mus musculus
• Experiment for Molecule Alteration: Genome extraction and sequencing assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: Tet(X3) and Tet(X4) inactivate all tetracyclines, including tigecycline and the newly FDA-approved eravacycline and omadacycline.

Key Molecule: Flavin-dependent monooxygenase (TETX3) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Enterobacteriaceae infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Acinetobacter baumannii 34AB; 509173
• In Vitro Model: Escherichia coli 47EC; 562
• In Vivo Model: ICR female mice model; Mus musculus
• Experiment for Molecule Alteration: Genome extraction and sequencing assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: Tet(X3) and Tet(X4) inactivate all tetracyclines, including tigecycline and the newly FDA-approved eravacycline and omadacycline.

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: TolC family outer membrane protein (TOLC) [2]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Acinetobacter baumannii AYE WT; 509173
• In Vitro Model: Acinetobacter baumannii AYE detaabuO; 509173
• In Vitro Model: Acinetobacter baumannii AYE detaabuO Omega abuO; 509173
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Disk diffusion test assay; E-strip test assay
• Mechanism Description: AbuO, an OMP, confers broad-spectrum antimicrobial resistance via active efflux in A. baumannii.

References

• Ref 1: Emergence of plasmid-mediated high-level tigecycline resistance genes in animals and humans. Nat Microbiol. 2019 Sep;4(9):1450-1456. doi: 10.1038/s41564-019-0445-2. Epub 2019 May 27.
• Ref 2: AbuO, a TolC-like outer membrane protein of Acinetobacter baumannii, is involved in antimicrobial and oxidative stress resistance. Antimicrob Agents Chemother. 2015 Feb;59(2):1236-45. doi: 10.1128/AAC.03626-14. Epub 2014 Dec 15.
• Ref 3: Molecular Epidemiology and Drug Resistant Mechanism of Carbapenem-Resistant Klebsiella pneumoniae in Elderly Patients With Lower Respiratory Tract Infection .Front Public Health. 2021 May 20;9:669173. doi: 10.3389/fpubh.2021.669173. eCollection 2021. 10.3389/fpubh.2021.669173