Drug Information

Drug (ID: DG00093) and It's Reported Resistant Information

• Name: Arbekacin
• Synonyms: Habekacin (TN)
• 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 (1 diseases)
  Bacterial infection [ICD-11: 1A00-1C4Z]; [2]
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Bacterial infection [ICD-11: 1A00-1C4Z]; [3]
• Target: Ribosome A (hRA); NOUNIPROTAC; [1]
• Formula: C22H44N6O10
• IsoSMILES: C1C[C@H]([C@H](O[C@@H]1CN)O[C@@H]2[C@H](C[C@H]([C@@H]([C@H]2O)O[C@@H]3[C@@H]([C@H]([C@@H]([C@H](O3)CO)O)N)O)NC(=O)[C@H](CCN)O)N)N
• InChI: 1S/C22H44N6O10/c23-4-3-12(30)20(34)28-11-5-10(26)18(37-21-9(25)2-1-8(6-24)35-21)17(33)19(11)38-22-16(32)14(27)15(31)13(7-29)36-22/h8-19,21-22,29-33H,1-7,23-27H2,(H,28,34)/t8-,9+,10-,11+,12-,13+,14-,15+,16+,17-,18+,19-,21+,22+/m0/s1
• InChIKey: MKKYBZZTJQGVCD-XTCKQBCOSA-N
• PubChem CID: 68682
• ChEBI ID: CHEBI:37922
• TTD Drug ID: D07JPC
• INTEDE ID: DR0130
• DrugBank ID: DB06696

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

  DISM: Drug Inactivation by Structure Modification

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: 16S rRNA (guanine(1405)-N(7))-methyltransferase (RMTA) [2]

• Resistant Disease: Pseudomonas aeruginosa infection [ICD-11: 1A00-1C4Z]
• Molecule Alteration: Expression; Intergeneric lateral gene transfer
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pseudomonas aeruginosa AR-2; 287
• Experiment for Molecule Alteration: PCR screening assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: The 16S rRNA methylase gene has undergone intergeneric horizontal gene transfer from some aminoglycoside producing microorganisms to Pseudomonas aeruginosa, which is called rmtA. rmtA protect bacterial 16S rRNA from intrinsic aminoglycosides by methylation.

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Aminoglycoside N(6')-acetyltransferase type 1 (A6AC1) [1]

• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pseudomonas aeruginosa PAO1; 208964
• In Vitro Model: Pseudomonas aeruginosa Nk0001; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0002; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0003; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0004; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0005; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0006; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0007; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0008; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0009; 287
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Micro-dilution method assay
• Mechanism Description: Recombinant AAC(6')-Iag protein showed aminoglycoside 6'-N-acetyltransferase activity using thin-layer chromatography (TLC) and MS spectrometric analysis. Escherichia coli carrying aac(6')-Iag showed resistance to amikacin, arbekacin, dibekacin, isepamicin, kanamycin, sisomicin, and tobramycin; but not to gentamicin.AAC(6')-Iag is a functional acetyltransferase that modifies alternate amino groups on the AGs.

Key Molecule: Aminoglycoside N-acetyltransferase AAC(6')-IAP [3]

• Resistant Disease: Lactobacillus casei infection [ICD-11: 1A00-1C4Z]
• Molecule Alteration: Expression; .
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: S. maltophilia JUNP350; N.A.
• Mechanism Description: Compared with vector control,?E. coli?expressing AAC(6')-Iap showed decreased susceptibilities to arbekacin, amikacin, dibekacin, isepamicin, neomycin, netilmicin, sisomicin, and tobramycin. Thin-layer chromatography (TLC) analysis revealed that all the aminoglycosides tested, except for apramycin and paromomycin, were acetylated by AAC(6')-Iap. These results indicated that?aac(6')-Iap?is a functional acetyltransferase that modifies the 6'-NH2?position of aminoglycosides and is involved in aminoglycoside resistance.

Key Molecule: Aminoglycoside N-acetyltransferase AAC(6')-IAP [3]

• Resistant Disease: Lactobacillus casei infection [ICD-11: 1A00-1C4Z]
• Molecule Alteration: Expression; T1080S+V1062L
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: Patient-derived S. maltophilia model; Homo sapiens
• Mechanism Description: S. maltophilia?JUNP350 was found to encode a novel 6'-N-aminoglycoside acetyltransferase, AAC(6')-Iap, consisting of 155 amino acids with 85.0% identity to AAC(6')-Iz.?E. coli?transformants expressing?aac(6')-Iap?were less susceptible to arbekacin, amikacin, dibekacin, isepamicin, neomycin, netilmicin, sisomicin and tobramycin. The recombinant AAC(6')-Iap protein acetylated all aminoglycosides tested, except for apramycin and paromomycin.

References

• Ref 1: Identification and characterization of a novel aac(6')-Iag associated with the blaIMP-1-integron in a multidrug-resistant Pseudomonas aeruginosa. PLoS One. 2013 Aug 12;8(8):e70557. doi: 10.1371/journal.pone.0070557. eCollection 2013.
• Ref 2: Acquisition of 16S rRNA methylase gene in Pseudomonas aeruginosa. Lancet. 2003 Dec 6;362(9399):1888-93. doi: 10.1016/S0140-6736(03)14959-8.
• Ref 3: Stenotrophomonas maltophilia from Nepal Producing Two Novel Antibiotic Inactivating Enzymes, a Class A beta-Lactamase KBL-1 and an Aminoglycoside 6'-N-Acetyltransferase AAC(6')-Iap. Microbiol Spectr. 2022 Aug 31;10(4):e0114322.