Drug Information

Drug (ID: DG00383) and It's Reported Resistant Information

• Name: Matromycin
• Synonyms: Oleandomycin; Amimycin; Matromycin; Romicil; Landomycin; 3922-90-5; UNII-P8ZQ646136; CHEBI:16869; P8ZQ646136; PA 775; Oleandomicina; Oleandomycine; Oleandomycinum; Oleandomycin [INN]; Antibiotic PA-105; Oleandomycine [French]; Oleandomycin [INN:BAN]; Oleandomycine [INN-French]; Oleandomycinum [INN-Latin]; Oleandomicina [INN-Spanish]; HSDB 7442; EINECS 223-495-7; AI3-50163; Prestwick3_000152; SCHEMBL3717; BSPBio_000284; BPBio1_000314; CHEMBL606258; Oleandomycin (chloroform solvate); BDBM234401; LMPK04000007; ZINC85432018; DB11442; NCGC00179617-01; 12-((2,6-Didesoxy-3-O-methyl-alpha-K-arabino-hexopyranosyl)oxy)-8-hydroxy-5,7,8,11,13,15-hexamethyl-14-((3,4,6-tridesoxy-3-dimethylamino-beta-D-xylo-hexopyranosyl)oxy)-1,9-dioxaspiro(2.13)hexadecan-4,10-dion; E704; HY-116010; AB00513809; CS-0063452; C01946; (3R,5R,6S,7R,8R,11R,12S,13R,14S,15S)-6-hydroxy-5,7,8,11,13,15-hexamethyl-4,10-dioxo-14-[3,4,6-trideoxy-3-(dimethylamino)-beta-D-xylo-hexopyranosyloxy]-1,9-dioxaspiro[2.13]hexadec-12-yl 2,6-dideoxy-3-O-methyl-alpha-L-arabino-hexopyranoside
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (2 diseases)
  Actinomycetoma [ICD-11: 1C43]; [1]
  Bacterial infection [ICD-11: 1A00-1C4Z]; [2]
  Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (1 diseases)
  Actinomycetoma [ICD-11: 1C43]; [3]
• Formula: C35H61NO12
• IsoSMILES: C[C@@H]1C[C@@H]([C@H]([C@@H](O1)O[C@H]2[C@H](C[C@@]3(CO3)C(=O)[C@@H]([C@H]([C@H]([C@H](OC(=O)[C@@H]([C@H]([C@@H]2C)O[C@H]4C[C@@H]([C@H]([C@@H](O4)C)O)OC)C)C)C)O)C)C)O)N(C)C
• InChI: 1S/C35H61NO12/c1-16-14-35(15-43-35)32(40)19(4)27(37)18(3)22(7)46-33(41)21(6)31(47-26-13-25(42-11)28(38)23(8)45-26)20(5)30(16)48-34-29(39)24(36(9)10)12-17(2)44-34/h16-31,34,37-39H,12-15H2,1-11H3/t16-,17+,18-,19+,20+,21+,22+,23-,24-,25-,26-,27-,28-,29+,30-,31-,34-,35+/m0/s1
• InChIKey: RZPAKFUAFGMUPI-QESOVKLGSA-N
• PubChem CID: 72493
• INTEDE ID: DR1189
• DrugBank ID: DB11442

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

  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

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: 23S ribosomal RNA methyltransferase Erm36 (ERM36) [2]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Micrococcus luteus infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Micrococcus luteus MAW843; 1270
• Experiment for Molecule Alteration: Sequence analysis
• Experiment for Drug Resistance: Agar diffusion test assay
• Mechanism Description: Erm(36) was most related (about 52-54% identity) to erythromycin-resistance proteins found in high-G+C Gram-positive bacteria and lead to drug resistance.

Actinomycetoma [ICD-11: 1C43]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Oleandomycin glycosyltransferase oleI (OLEL) [1]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Streptomyces infection [ICD-11: 1C43.6]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli C41(DE3); 469008
• Experiment for Molecule Alteration: Linked enzyme activity assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: Glycosylation of macrolide antibiotics confers host cell immunity from endogenous and exogenous agents. The Streptomyces antibioticus glycosyltransferases, OleI, glycosylate and inactivate oleandomycin.

Key Molecule: srmA open reading frame gimA (GIMA) [4]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Streptomyces ambbyaciens infection [ICD-11: 1C43.0]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli; 668369
• In Vitro Model: Escherichia coli strain S17.1; 1227813
• In Vitro Model: Micrococcus luteus strain Cgr; 1270
• In Vitro Model: Micrococcus luteus strain DSM1790; 1270
• In Vitro Model: Streptomyces ambofaciens strain ATCC 23877; 278992
• In Vitro Model: Streptomyces ambofaciens strain OS41.99; 1954
• In Vitro Model: Streptomyces ambofaciens strain OS41.99NP; 1954
• In Vitro Model: Streptomyces ambofaciens strain OS81; 1954
• In Vitro Model: Streptomyces lividans strain OS456; 1916
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Observation of growth inhibition zones assay
• Mechanism Description: With UDP-[14C]glucose as the cofactor, crude S30 extracts from OS456(pOS41.90) were tested on various macrolides. Among those, chalcomycin was the most active substrate. Methymycin, tylosin, pikromycin, and rosaramicin were four of the best substrates. Oleandomycin, josamycin, and carbomycin were glycosylated to a lesser extent. Macrolides that were found to be as poor substrates of GimA as lankamycin were erythromycin and angolamycin. Spiramycin was also a very poor substrate.

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ATP-binding protein (ABP) [5]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Streptomyces antibioticus infection [ICD-11: 1C43.1]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Streptomyces antibioticus strain; 1890
• Experiment for Molecule Alteration: Fluorescence measurements assay
• Mechanism Description: The OleB protein ofStreptomyces antibioticus, oleandomycin (OM) producer, constitutes an ATP-binding cassette transporter containing two nucleotide-binding domains and is involved in OM resistance and its secretion in this producer strain.

Key Molecule: ATP-binding protein (ABP) [3]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Streptomyces antibioticus infection [ICD-11: 1C43.1]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Streptomyces albus J1074; 457425
• In Vitro Model: Streptomyces lividans strain Tk21; 1916
• In Vitro Model: Escherichia coli strain ED8767; 562
• In Vitro Model: Escherichia coli strain TGI; 83333
• In Vitro Model: Streptomyces antibioticu strain ATCC 11891; 1890
• Experiment for Molecule Alteration: DNA hybridizations assay
• Mechanism Description: Three different DNA fragments of an oleandomycin producer, Streptomyces antibioticus, conferring oleandomycin resistance were cloned in plasmid pIJ702 and expressed in Streptomyces lividans and in Streptomyces albus. These oleandomycin resistance determinants were designated as oleA (pOR400), oleB (pOR501) and oleC (pOR800). The oleC (orf4) gene product had a hydrophilic profile and showed important similarity with proteins containing typical ATP-binding domains characteristic of the ABC-transporter superfamily and involved in membrane transport and, particularly, with several genes conferring resistance to various macrolide antibiotics and anticancer drugs.

References

• Ref 1: The crystal structure of two macrolide glycosyltransferases provides a blueprint for host cell antibiotic immunity. Proc Natl Acad Sci U S A. 2007 Mar 27;104(13):5336-41. doi: 10.1073/pnas.0607897104. Epub 2007 Mar 21.
• Ref 2: Plasmid-borne macrolide resistance in Micrococcus luteus. Microbiology (Reading). 2002 Aug;148(Pt 8):2479-2487. doi: 10.1099/00221287-148-8-2479.
• Ref 3: Streptomyces antibioticus contains at least three oleandomycin-resistance determinants, one of which shows similarity with proteins of the ABC-transporter superfamily. Mol Microbiol. 1993 May;8(3):571-82. doi: 10.1111/j.1365-2958.1993.tb01601.x.
• Ref 4: Characterization of a glycosyl transferase inactivating macrolides, encoded by gimA from Streptomyces ambofaciens. Antimicrob Agents Chemother. 1998 Oct;42(10):2612-9. doi: 10.1128/AAC.42.10.2612.
• Ref 5: Interaction between ATP, oleandomycin and the OleB ATP-binding cassette transporter of Streptomyces antibioticus involved in oleandomycin secretion. Biochem J. 1997 Jan 1;321 ( Pt 1)(Pt 1):139-44. doi: 10.1042/bj3210139.