Drug Information

Drug (ID: DG00372) and It's Reported Resistant Information

• Name: Colistin B
• Synonyms: Colistin b; Polymyxin E2; 7239-48-7; UNII-B142O7Y03E; CHEBI:59673; B142O7Y03E; polymyxin E2 sulfate; N-[(2S)-4-amino-1-[[(2S,3R)-1-[[(2S)-4-amino-1-oxo-1-[[(3S,6S,9S,12S,15R,18S,21S)-6,9,18-tris(2-aminoethyl)-3-[(1R)-1-hydroxyethyl]-12,15-bis(2-methylpropyl)-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptazacyclotricos-21-yl]amino]butan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxobutan-2-yl]-6-methylheptanamide; 4,10-anhydro[N-(6-methylheptanoyl)-L-2,4-diaminobutanoyl-L-threonyl-L-2,4-diaminobutanoyl-L-2,4-diaminobutanoyl-L-2,4-diaminobutanoyl-D-leucyl-L-leucyl-L-2,4-diaminobutanoyl-L-2,4-diaminobutanoyl-L-threonine]; SCHEMBL1860364; CHEMBL1089240; Polymyxin E2 sulfate (P056); Q27126844; UNII-Z67X93HJG1 component KNIWPHSUTGNZST-SSWRVQTPSA-N; 30387-41-8
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Bacterial infection [ICD-11: 1A00-1C4Z]; [1]
  Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (1 diseases)
  Gram-negative bacterial infection [ICD-11: 1B74-1G40]; [2]
• Formula: C52H98N16O13
• IsoSMILES: C[C@H]([C@H]1C(=O)NCC[C@@H](C(=O)N[C@H](C(=O)N[C@@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N1)CCN)CCN)CC(C)C)CC(C)C)CCN)NC(=O)[C@H](CCN)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCN)NC(=O)CCCCC(C)C)O
• InChI: 1S/C52H98N16O13/c1-27(2)11-9-10-12-40(71)59-32(13-19-53)47(76)68-42(31(8)70)52(81)64-35(16-22-56)44(73)63-37-18-24-58-51(80)41(30(7)69)67-48(77)36(17-23-57)61-43(72)33(14-20-54)62-49(78)38(25-28(3)4)66-50(79)39(26-29(5)6)65-45(74)34(15-21-55)60-46(37)75/h27-39,41-42,69-70H,9-26,53-57H2,1-8H3,(H,58,80)(H,59,71)(H,60,75)(H,61,72)(H,62,78)(H,63,73)(H,64,81)(H,65,74)(H,66,79)(H,67,77)(H,68,76)/t30-,31-,32+,33+,34+,35+,36+,37+,38+,39-,41+,42+/m1/s1
• InChIKey: KNIWPHSUTGNZST-SSWRVQTPSA-N
• PubChem CID: 25138298

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

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: Colistin resistance PEtN transferase (ICRMc ) [1]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli BW25113; 679895
• Mechanism Description: Diverse covalent modifications of LPS, which include among others the addition of phosphoethanolamine (PEtN) groups are thought to alter the physical properties of the outer membrane, resulting in polymyxin resistance. The increased clinical and agricultural use of colistin has been linked to the mobilization and transfer of colistin resistance elements to human pathogenic bacteria.53 resistance elements to human pathogenic bacteria.

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

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Colistin resistance protein (MCR-3.3-Unclear) [2]

• Molecule Alteration: Mutation; .
• Resistant Disease: Gram-negative bacterial infection [ICD-11: 1B74-1G40]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli ATCC 25922; 1322345
• In Vitro Model: Aeromonas veronii 172; 654
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: This strain showed resistance to both Beta-lactams and phenicols and had borderline susceptibility to colistin, which was mediated by mcr-3.3 alone.

References

• Ref 1: Substrate Recognition by a Colistin Resistance Enzyme from Moraxella catarrhalis. ACS Chem Biol. 2018 May 18;13(5):1322-1332. doi: 10.1021/acschembio.8b00116. Epub 2018 Apr 19.
• Ref 2: Chromosome-Mediated mcr-3 Variants in Aeromonas veronii from Chicken Meat. Antimicrob Agents Chemother. 2017 Oct 24;61(11):e01272-17. doi: 10.1128/AAC.01272-17. Print 2017 Nov.