Drug Information

Drug (ID: DG00374) and It's Reported Resistant Information

• Name: Pristinamycin IIA
• Synonyms: Virginiamycin m1; Streptogramin A; Mikamycin A; Pristinamycin IIA; Ostreogrycin a; Virginiamycin Factor M1; 21411-53-0; UNII-8W4UOL59AZ; 8W4UOL59AZ; CHEBI:9997; VERNAMYCIN A; NSC87434; NSC 244426; Vernamycin A & B mixture; SCHEMBL673193; CHEMBL1236670; HY-N6686; EINECS 244-376-6; MFCD00869411; NSC 87432; NSC-87434; Vernamycin A & vernamycin B (1:1); DB01669; Vernamycin A, mixture with vernamycin B; VERNAMYCIN A & B MIXTURE (1:1); CS-0019826; Virginiamycin M1 100 microg/mL in Acetonitrile; UNII-4O8O7Q7IU4 component DAIKHDNSXMZDCU-FQTGFAPKSA-N; (3R,4R,5E,10E,12E,14S)-14-hydroxy-3-isopropyl-4,12-dimethyl-8,9,14,15,24,25-hexahydro-1H,3H,22H-21,18-(azeno)pyrrolo[2,1-c][1,8,4,19]dioxadiazacyclotetracosine-1,7,16,22(4H,17H)-tetrone; (3R,4R,5E,10E,12E,14S)-14-hydroxy-4,12-dimethyl-3-(1-methylethyl)-8,9,14,15,24,25-hexahydro-1H,3H,22H-21,18-(azeno)pyrrolo[2,1-c][1,8,4,19]dioxadiazacyclotetracosine-1,7,16,22(4H,17H)-tetrone; 8,9,14,15,24,25-Hexahydro-14-hydroxy-3-isopropyl-4,12-dimethyl-3H-21,18-nitrilo-1H,22H-pyrrolo(2,1-c)(1,8,4,19)dioxadiazacyclotetracosine-1,7,16,22(4H,17H)-tetrone; 8,9,14,15,24,25-Hexahydro-14-hydroxy-4,12-dimethyl-3-(1-methylethyl)-3H-21,18-nitrilo-1H,22H-pyrrolo(2,1-c)(1,8,4,19)dioxadiazacyclotetracosine-1,7,16,22(4H,17H)-tetrone
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Bacterial infection [ICD-11: 1A00-1C4Z]; [1]
• Formula: C28H35N3O7
• IsoSMILES: C[C@@H]1/C=C/C(=O)NC/C=C/C(=C/[C@H](CC(=O)CC2=NC(=CO2)C(=O)N3CCC=C3C(=O)O[C@@H]1C(C)C)O)/C
• InChI: 1S/C28H35N3O7/c1-17(2)26-19(4)9-10-24(34)29-11-5-7-18(3)13-20(32)14-21(33)15-25-30-22(16-37-25)27(35)31-12-6-8-23(31)28(36)38-26/h5,7-10,13,16-17,19-20,26,32H,6,11-12,14-15H2,1-4H3,(H,29,34)/b7-5+,10-9+,18-13+/t19-,20-,26-/m1/s1
• InChIKey: DAIKHDNSXMZDCU-FQTGFAPKSA-N
• PubChem CID: 5459319
• DrugBank ID: DB01669

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

  IDUE: Irregularity in Drug Uptake and Drug Efflux

  UAPP: Unusual Activation of Pro-survival Pathway

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 rRNA (Adenine(2503)-C(8))-methyltransferase ClbA (CIBA) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli AS19; 562
• In Vitro Model: Escherichia coli JW2501-1; 562
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: The cfr gene encodes the Cfr methyltransferase that methylates a single adenine in the peptidyl transferase region of bacterial ribosomes.Expression of the genes was induced in Escherichia coli, and MICs for selected antibiotics indicate that the cfr-like genes confer resistance to PhLOPSa (phenicol, lincosamide, oxazolidinone, pleuromutilin, and streptogramin A) antibiotics in the same way as the cfr gene.The Cfr-like proteins ClbA, ClbC, and ClbB confer a resistance pattern similar to that of the Cfr methyltransferase.

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ABC superfamily ATP binding cassette transporter (ABCCT) [2], [3]

• 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 TOP10; 83333
• In Vitro Model: Staphylococcus aureus RN4220; 1280
• In Vitro Model: Staphylococcus saprophyticus ATCC 15305; 342451
• In Vitro Model: Staphylococcus sciuri ATCC 29059; 1296
• In Vitro Model: Staphylococcus sciuri ATCC 29062; 1296
• In Vitro Model: Staphylococcus sciuri ATCC 700058; 1296
• In Vitro Model: Staphylococcus sciuri ATCC 700061; 1296
• In Vitro Model: Staphylococcus sciuri BL2; 1296
• In Vitro Model: Staphylococcus sciuri SS226; 1296
• In Vitro Model: Staphylococcus sciuri SVv1; 1296
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Disk diffusion test assay; E-strip test assay
• Mechanism Description: Efflux-mediated resistance to MLS antibiotics in staphylococci relies on the ATPase activity of a very special kind of ATP-binding cassette (ABC) protein.By whole-genome sequencing of strain ATCC 29059, we identified a candidate gene that encodes an ATP-binding cassette protein similar to the Lsa and VmlR resistance determinants. Isolation and reverse transcription-quantitative PCR (qRT-PCR) expression studies confirmed that Sal(A) can confer a moderate resistance to lincosamides (8 times the MIC of lincomycin) and a high-level resistance to streptogramins A. The chromosomal location of sal(A) between two housekeeping genes of the staphylococcal core genome supports the gene's ancient origins and thus innate resistance to these antimicrobials within S. sciuri subspecies.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Colibactin polyketide synthase ClbC (CLBC) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli AS19; 562
• In Vitro Model: Escherichia coli JW2501-1; 562
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: The cfr gene encodes the Cfr methyltransferase that methylates a single adenine in the peptidyl transferase region of bacterial ribosomes.Expression of the genes was induced in Escherichia coli, and MICs for selected antibiotics indicate that the cfr-like genes confer resistance to PhLOPSa (phenicol, lincosamide, oxazolidinone, pleuromutilin, and streptogramin A) antibiotics in the same way as the cfr gene.The Cfr-like proteins ClbA, ClbC, and ClbB confer a resistance pattern similar to that of the Cfr methyltransferase.

References

• Ref 1: The order Bacillales hosts functional homologs of the worrisome cfr antibiotic resistance gene. Antimicrob Agents Chemother. 2012 Jul;56(7):3563-7. doi: 10.1128/AAC.00673-12. Epub 2012 Apr 30.
• Ref 2: Characterization of sal(A), a novel gene responsible for lincosamide and streptogramin A resistance in Staphylococcus sciuri. Antimicrob Agents Chemother. 2014 Jun;58(6):3335-41. doi: 10.1128/AAC.02797-13. Epub 2014 Mar 31.
• Ref 3: Identification of ABC transporter genes conferring combined pleuromutilin-lincosamide-streptogramin A resistance in bovine methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococci. Vet Microbiol. 2015 Jun 12;177(3-4):353-8. doi: 10.1016/j.vetmic.2015.03.027. Epub 2015 Apr 8.