Drug Information

Drug (ID: DG00386) and It's Reported Resistant Information

• Name: Tiamulin
• Synonyms: Tiamulin; 55297-95-5; Thiamutilin; Tiamulina; Tiamuline; Tiamulinum; Tiamulin pamoate; UNII-E38WZ4U54R; Denagard (TN); E38WZ4U54R; CHEBI:44137; Denagard; Tiavet P; (3aS,4R,5S,6S,8R,9R,9aR,10R)-6-ethenyl-5-hydroxy-4,6,9,10-tetramethyl-1-oxodecahydro-3a,9-propanocyclopenta[8]annulen-8-yl {[2-(diethylamino)ethyl]sulfanyl}acetate; Tiamulina [Italian]; AC1LCVRY; Tiamuline [INN-French]; Tiamulinum [INN-Latin]; Tiamulina [INN-Spanish]; HSDB 7026; Tiamulin [USAN:USP:INN:BAN]; EINECS 259-580-0; BRN 2229396; Tiamulin (USP/INN); SQ 14055; CHEMBL1234521; DTXSID2046701; SCHEMBL18232392; 14-Deoxy-14-((2-diethylaminoethyl-thio)-acetoxy)mutiline; (hydroxy-tetramethyl-oxo-vinyl-[ ]yl) 2-(2-diethylaminoethylsulfanyl)acetate; HY-B2060; ZINC4217557; BBL036673; STL559052; DB11468; ((2-(Diethylamino)ethyl)thio)-, 6-ethenyldecahydro-5-hydroxy-4,6,9,10-tetramethyl-1-oxo-3a,9-propano-3aH-cyclopentacycloocten-8-yl ester (3aS-(3aalpha,4beta,5alpha,6alpha,8beta,9alpha,9abeta,10S*))-; ((2-(Diethylamino)ethyl)thio)acetic acid 8-ester with (3aS,4R,5S,6S,8R,9R,9aR,10R)-octahydro-5,8-dihydroxy-4,6,9,10)-tetramethyl-6-vinyl-3a,9-propano-3aH-cyclopentacycloocten-1(4H)-one; ((2-(Diethylamino)ethyl)thio)acetic acid 8-ester with (3aS,4R,5S,6S,8R,9R,9aR,10R)-octahydro-5,8-dihydroxy-4,6,9,10-tetramethyl-6-vinyl-3a,9-propano-3aH-cyclopentacycloocten-1(4H)-one; Acetic acid, [[2-(diethylamino)ethyl]thio]-,(3aS,4R,5S,6S,8R,9R,9aR,10R)-6-ethenyldecahydro-5-hydroxy-4,6,9,10-tetramethyl-1-oxo-3a,9-propano-3aH-cyclopentacycloocten-8-ylester; SO 14055; CS-0014153; D06127; Q7800111; (3aS,4R,5S,6S,8R,9R,9aR,10R)-5-hydroxy-4,6,9,10-tetramethyl-1-oxo-6-vinyldecahydro-3a,9-propanocyclopenta[8]annulen-8-yl {[2-(diethylamino)ethyl]sulfanyl}acetate; (3aS,4R,5S,6S,8R,9R,9aR,10R)-6-Ethenyl-5-hydroxy- 4,6,9,10-tetramethyl-1-oxodecahydro-3a,9-propano-3aH-cyclopentacycloocten-8-yl [[2-(diethylamino)ethyl]sulfanyl]acetate; 3-[2-[3-[[4-[[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-4-hydroxy-3-phosphonooxy-tetrahydrofuran-2-yl]methoxy-hydroxy-phosphoryl]oxy-hydroxy-phosphoryl]oxy-2-hydroxy-3,3-dimethyl-butanoyl]amino]propanoylamino]ethylsulfanylcarbonyl]-4-hydroxy-4-(2-naphthyl)butanoic acid; Acetic acid, ((2-(diethylamino)ethyl)thio)-, (3aS,4R,5S,6S,8R,9R,9aR,10R)-6-ethenyldecahydro-5-hydroxy-4,6,9,10-tetramethyl-1-oxo-3a,9-propano-3aH-cyclopentacycloocten-8-yl ester; Acetic acid, ((2-(diethylamino)ethyl)thio)-, 6-ethenyldecahydro-5-hydroxy-4,6,9,10-tetramethyl-1-oxo-3a,9-propano-3aH-cyclopentacycloocten-8-yl ester (3aS-(3aalpha,4beta,5alpha,6alpha,8beta,9alpha,9abeta,10S*))-
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (9 diseases)
  Bacteremia [ICD-11: MA15]; [1]
  Bacterial infection [ICD-11: 1A00-1C4Z]; [2], [3]
  Infective endocarditis [ICD-11: BB40]; [1]
  Joint direct infection [ICD-11: FA10]; [1]
  Non-tuberculous mycobacteria infection [ICD-11: 1B21]; [1]
  Osteomyelitis/osteitis [ICD-11: FB84]; [1]
  Respiratory trac infection [ICD-11: CA45]; [1]
  Tissue pyogenic bacterial infection [ICD-11: 1B7Y]; [1]
  Urinary tract infection [ICD-11: GC08]; [1]
  Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (1 diseases)
  Bacterial infection [ICD-11: 1A00-1C4Z]; [4]
• Formula: C28H47NO4S
• IsoSMILES: CCN(CC)CCSCC(=O)O[C@@H]1C[C@@]([C@H]([C@@H]([C@@]23CC[C@H]([C@@]1([C@@H]2C(=O)CC3)C)C)C)O)(C)C=C
• InChI: 1S/C28H47NO4S/c1-8-26(6)17-22(33-23(31)18-34-16-15-29(9-2)10-3)27(7)19(4)11-13-28(20(5)25(26)32)14-12-21(30)24(27)28/h8,19-20,22,24-25,32H,1,9-18H2,2-7H3/t19-,20+,22-,24+,25+,26-,27+,28+/m1/s1
• InChIKey: UURAUHCOJAIIRQ-QGLSALSOSA-N
• PubChem CID: 656958
• DrugBank ID: DB11468

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: Carboxymethylenebutenolidase (CLCD) [4]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli AS19; 562
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: The Cfr RNA methyltransferase causes multiple resistances to peptidyl transferase inhibitors by methylation of A2503 23S rRNA.clcD codes the same enzyme.

Key Molecule: Ribosomal RNA large subunit methyltransferase (CFR ) [5]

• 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 TOP10; 83333
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: Cfr confers resistance to antibiotics binding to the peptidyl transferase center on the ribosome.The primary product of the Cfr-mediated methylation is 8-methyladenosine (m8A), a new natural RNA modification that has so far not been seen at sites other than A2503 in 23S rRNA.

Key Molecule: 23S rRNA (Adenine(2503)-C(8))-methyltransferase ClbA (CIBA) [6]

• 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 transporter ATP-binding protein (ABCP) [2], [3]

• Molecule Alteration: Missense mutation; p.T450I
• 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: Enterococcus faecium HM1070; 1352
• In Vitro Model: Enterococcus faecium UCN80; 1352
• Experiment for Molecule Alteration: Whole genome sequence assay
• Mechanism Description: ABC systems constitute one of the largest families of proteins, with most of them being involved in import and export, often called ABC transporters.Several of these class 2 ABC systems have been involved in MLS resistance, such as Msr-, Vga-, or Lsa-like proteins.The observed profile of cross-resistance to lincosamides, streptogramins A, and pleuromutilins conferred by Eat(A)v was similar to those conferred by other Lsa-like proteins.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Colibactin polyketide synthase ClbC (CLBC) [6]

• 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.

Non-tuberculous mycobacteria infection [ICD-11: 1B21]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ABC protein lsaC (lsaC-Unclear) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Streptococcus agalactiae infection [ICD-11: 1B21.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli TOP10; 83333
• In Vitro Model: Staphylococcus aureus ATCC 29213; 1280
• In Vitro Model: Streptococcus agalactiae UCN70; 1311
• In Vitro Model: Streptococcus agalactiae isolates; 1311
• In Vitro Model: Streptococcus agalactiae BM132; 1319
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Expression of this novel gene, named lsa(C), in S. agalactiae BM132 after cloning led to an increase in MICs of lincomycin (0.06 to 4 ug/ml), clindamycin (0.03 to 2 ug/ml), dalfopristin (2 to >32 ug/ml), and tiamulin (0.12 to 32 ug/ml), whereas no change in MICs of erythromycin (0.06 ug/ml), azithromycin (0.03 ug/ml), spiramycin (0.25 ug/ml), telithromycin (0.03 ug/ml), and quinupristin (8 ug/ml) was observed. The phenotype was renamed the LS(A)P phenotype on the basis of cross-resistance to lincosamides, streptogramins A, and pleuromutilins.

Tissue pyogenic bacterial infection [ICD-11: 1B7Y]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ABC protein lsaC (lsaC-Unclear) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Streptococcus agalactiae infection [ICD-11: 1B21.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli TOP10; 83333
• In Vitro Model: Staphylococcus aureus ATCC 29213; 1280
• In Vitro Model: Streptococcus agalactiae UCN70; 1311
• In Vitro Model: Streptococcus agalactiae isolates; 1311
• In Vitro Model: Streptococcus agalactiae BM132; 1319
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Expression of this novel gene, named lsa(C), in S. agalactiae BM132 after cloning led to an increase in MICs of lincomycin (0.06 to 4 ug/ml), clindamycin (0.03 to 2 ug/ml), dalfopristin (2 to >32 ug/ml), and tiamulin (0.12 to 32 ug/ml), whereas no change in MICs of erythromycin (0.06 ug/ml), azithromycin (0.03 ug/ml), spiramycin (0.25 ug/ml), telithromycin (0.03 ug/ml), and quinupristin (8 ug/ml) was observed. The phenotype was renamed the LS(A)P phenotype on the basis of cross-resistance to lincosamides, streptogramins A, and pleuromutilins.

ICD-11: Circulatory system diseases

Infective endocarditis [ICD-11: BB40]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ABC protein lsaC (lsaC-Unclear) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Streptococcus agalactiae infection [ICD-11: 1B21.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli TOP10; 83333
• In Vitro Model: Staphylococcus aureus ATCC 29213; 1280
• In Vitro Model: Streptococcus agalactiae UCN70; 1311
• In Vitro Model: Streptococcus agalactiae isolates; 1311
• In Vitro Model: Streptococcus agalactiae BM132; 1319
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Expression of this novel gene, named lsa(C), in S. agalactiae BM132 after cloning led to an increase in MICs of lincomycin (0.06 to 4 ug/ml), clindamycin (0.03 to 2 ug/ml), dalfopristin (2 to >32 ug/ml), and tiamulin (0.12 to 32 ug/ml), whereas no change in MICs of erythromycin (0.06 ug/ml), azithromycin (0.03 ug/ml), spiramycin (0.25 ug/ml), telithromycin (0.03 ug/ml), and quinupristin (8 ug/ml) was observed. The phenotype was renamed the LS(A)P phenotype on the basis of cross-resistance to lincosamides, streptogramins A, and pleuromutilins.

ICD-12: Respiratory system diseases

Respiratory trac infection [ICD-11: CA45]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ABC protein lsaC (lsaC-Unclear) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Streptococcus agalactiae infection [ICD-11: 1B21.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli TOP10; 83333
• In Vitro Model: Staphylococcus aureus ATCC 29213; 1280
• In Vitro Model: Streptococcus agalactiae UCN70; 1311
• In Vitro Model: Streptococcus agalactiae isolates; 1311
• In Vitro Model: Streptococcus agalactiae BM132; 1319
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Expression of this novel gene, named lsa(C), in S. agalactiae BM132 after cloning led to an increase in MICs of lincomycin (0.06 to 4 ug/ml), clindamycin (0.03 to 2 ug/ml), dalfopristin (2 to >32 ug/ml), and tiamulin (0.12 to 32 ug/ml), whereas no change in MICs of erythromycin (0.06 ug/ml), azithromycin (0.03 ug/ml), spiramycin (0.25 ug/ml), telithromycin (0.03 ug/ml), and quinupristin (8 ug/ml) was observed. The phenotype was renamed the LS(A)P phenotype on the basis of cross-resistance to lincosamides, streptogramins A, and pleuromutilins.

ICD-15: Musculoskeletal/connective-tissue diseases

Joint direct infection [ICD-11: FA10]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ABC protein lsaC (lsaC-Unclear) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Streptococcus agalactiae infection [ICD-11: 1B21.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli TOP10; 83333
• In Vitro Model: Staphylococcus aureus ATCC 29213; 1280
• In Vitro Model: Streptococcus agalactiae UCN70; 1311
• In Vitro Model: Streptococcus agalactiae isolates; 1311
• In Vitro Model: Streptococcus agalactiae BM132; 1319
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Expression of this novel gene, named lsa(C), in S. agalactiae BM132 after cloning led to an increase in MICs of lincomycin (0.06 to 4 ug/ml), clindamycin (0.03 to 2 ug/ml), dalfopristin (2 to >32 ug/ml), and tiamulin (0.12 to 32 ug/ml), whereas no change in MICs of erythromycin (0.06 ug/ml), azithromycin (0.03 ug/ml), spiramycin (0.25 ug/ml), telithromycin (0.03 ug/ml), and quinupristin (8 ug/ml) was observed. The phenotype was renamed the LS(A)P phenotype on the basis of cross-resistance to lincosamides, streptogramins A, and pleuromutilins.

Osteomyelitis/osteitis [ICD-11: FB84]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ABC protein lsaC (lsaC-Unclear) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Streptococcus agalactiae inection [ICD-11: FB84.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli TOP10; 83333
• In Vitro Model: Staphylococcus aureus ATCC 29213; 1280
• In Vitro Model: Streptococcus agalactiae UCN70; 1311
• In Vitro Model: Streptococcus agalactiae isolates; 1311
• In Vitro Model: Streptococcus agalactiae BM132; 1319
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Expression of this novel gene, named lsa(C), in S. agalactiae BM132 after cloning led to an increase in MICs of lincomycin (0.06 to 4 ug/ml), clindamycin (0.03 to 2 ug/ml), dalfopristin (2 to >32 ug/ml), and tiamulin (0.12 to 32 ug/ml), whereas no change in MICs of erythromycin (0.06 ug/ml), azithromycin (0.03 ug/ml), spiramycin (0.25 ug/ml), telithromycin (0.03 ug/ml), and quinupristin (8 ug/ml) was observed. The phenotype was renamed the LS(A)P phenotype on the basis of cross-resistance to lincosamides, streptogramins A, and pleuromutilins.

ICD-16: Genitourinary system diseases

Urinary tract infection [ICD-11: GC08]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ABC protein lsaC (lsaC-Unclear) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Klebsiella pneumoniae [ICD-11: CA40.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli TOP10; 83333
• In Vitro Model: Staphylococcus aureus ATCC 29213; 1280
• In Vitro Model: Streptococcus agalactiae UCN70; 1311
• In Vitro Model: Streptococcus agalactiae isolates; 1311
• In Vitro Model: Streptococcus agalactiae BM132; 1319
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Expression of this novel gene, named lsa(C), in S. agalactiae BM132 after cloning led to an increase in MICs of lincomycin (0.06 to 4 ug/ml), clindamycin (0.03 to 2 ug/ml), dalfopristin (2 to >32 ug/ml), and tiamulin (0.12 to 32 ug/ml), whereas no change in MICs of erythromycin (0.06 ug/ml), azithromycin (0.03 ug/ml), spiramycin (0.25 ug/ml), telithromycin (0.03 ug/ml), and quinupristin (8 ug/ml) was observed. The phenotype was renamed the LS(A)P phenotype on the basis of cross-resistance to lincosamides, streptogramins A, and pleuromutilins.

ICD-21: Symptoms/clinical signs/unclassified clinical findings

Bacteremia [ICD-11: MA15]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ABC protein lsaC (lsaC-Unclear) [1]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Streptococcus agalactiae infection [ICD-11: 1B21.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli TOP10; 83333
• In Vitro Model: Staphylococcus aureus ATCC 29213; 1280
• In Vitro Model: Streptococcus agalactiae UCN70; 1311
• In Vitro Model: Streptococcus agalactiae isolates; 1311
• In Vitro Model: Streptococcus agalactiae BM132; 1319
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Expression of this novel gene, named lsa(C), in S. agalactiae BM132 after cloning led to an increase in MICs of lincomycin (0.06 to 4 ug/ml), clindamycin (0.03 to 2 ug/ml), dalfopristin (2 to >32 ug/ml), and tiamulin (0.12 to 32 ug/ml), whereas no change in MICs of erythromycin (0.06 ug/ml), azithromycin (0.03 ug/ml), spiramycin (0.25 ug/ml), telithromycin (0.03 ug/ml), and quinupristin (8 ug/ml) was observed. The phenotype was renamed the LS(A)P phenotype on the basis of cross-resistance to lincosamides, streptogramins A, and pleuromutilins.

References

• Ref 1: Cross-resistance to lincosamides, streptogramins A, and pleuromutilins due to the lsa(C) gene in Streptococcus agalactiae UCN70. Antimicrob Agents Chemother. 2011 Apr;55(4):1470-4. doi: 10.1128/AAC.01068-10. Epub 2011 Jan 18.
• Ref 2: Comparative analysis of the first complete Enterococcus faecium genome. J Bacteriol. 2012 May;194(9):2334-41. doi: 10.1128/JB.00259-12. Epub 2012 Feb 24.
• Ref 3: Genetic basis for in vitro and in vivo resistance to lincosamides, streptogramins A, and pleuromutilins (LSAP phenotype) in Enterococcus faecium. Antimicrob Agents Chemother. 2013 Sep;57(9):4463-9. doi: 10.1128/AAC.01030-13. Epub 2013 Jul 8.
• Ref 4: A cfr-like gene from Clostridium difficile confers multiple antibiotic resistance by the same mechanism as the cfr gene. Antimicrob Agents Chemother. 2015 Sep;59(9):5841-3. doi: 10.1128/AAC.01274-15. Epub 2015 Jul 6.
• Ref 5: Distinction between the Cfr methyltransferase conferring antibiotic resistance and the housekeeping RlmN methyltransferase. Antimicrob Agents Chemother. 2013 Aug;57(8):4019-26. doi: 10.1128/AAC.00448-13. Epub 2013 Jun 10.
• Ref 6: 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.