Drug Information

Drug (ID: DG00251) and It's Reported Resistant Information

• Name: Clindamycin
• Synonyms: Antirobe; CLDM; CLY; Chlolincocin; Chlorlincocin; Chlorodeoxylincomycin; Chlorolincomycin; Cleocin; ClindaDerm; Clindamicina; Clindamycine; Clindamycinum; Clinimycin; Dalacine; Klimicin; Sobelin; Zindaclin; Cleocin HCl; Cleocin T Gel; Cleocin T Lotion; Cleocin T Topical Solution; Clindamycine [French]; Dalacin C; Dalacin C Flavored Granules; Dalacin C Phosphate; Dalacin T Topical Solution; ResiDerm A; Klindan 300; U 21251; Cleocin (TN); Clindacin (TN); Clindamicina [INN-Spanish]; Clindamycin & Interleukin 12; Clindamycin & VRC3375; Clindamycine [INN-French]; Clindamycinum [INN-Latin]; Dalacin (TN); Evoclin (TN); U-21251; CLINDA & IL-12; Clindamycin (USAN/INN); Clindamycin [USAN:BAN:INN]; U-21,251; 7(S)-Chloro-7-deoxylincomycin; 7-CDL; 7-Chloro-7-deoxylincomycin; 7-Chlorolincomycin; 7-Deoxy-7(S)-chlorolincomycin
• Indication:
  In total 1 Indication(s)
  Acne vulgaris [ICD-11: ED80]; Approved; [1], [2], [3], [4], [5]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (16 diseases)
  Bacillus infection [ICD-11: 1C4Y]; [6]
  Bacteremia [ICD-11: MA15]; [7]
  Bacterial infection [ICD-11: 1A00-1C4Z]; [8]
  Infective endocarditis [ICD-11: BB40]; [7]
  Intra-abdominal infection [ICD-11: DC51]; [9]
  Joint direct infection [ICD-11: FA10]; [7]
  Mycobacterial diseases [ICD-11: 1B2Z ]; [10]
  Non-tuberculous mycobacteria infection [ICD-11: 1B21]; [7]
  Osteomyelitis/osteitis [ICD-11: FB84]; [7]
  Pneumonia [ICD-11: CA40]; [11]
  Respiratory trac infection [ICD-11: CA45]; [7]
  Streptococcal pharyngitis [ICD-11: 1B51]; [12]
  Surgical wound infection [ICD-11: NE81]; [13]
  Tissue pyogenic bacterial infection [ICD-11: 1B7Y]; [7]
  Ulcer [ICD-11: EH90]; [14]
  Urinary tract infection [ICD-11: GC08]; [7]
  Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (4 diseases)
  Bacillus infection [ICD-11: 1C4Y]; [15]
  Bacterial infection [ICD-11: 1A00-1C4Z]; [16]
  Clostridioides difficile intestinal infection [ICD-11: 1A04]; [17]
  Pasteurellosis [ICD-11: 1B99]; [18]
• Target: Bacterial 50S ribosomal RNA (Bact 50S rRNA); NOUNIPROTAC; [1]
• Formula: C18H33ClN2O5S
• IsoSMILES: CCC[C@@H]1C[C@H](N(C1)C)C(=O)N[C@@H]([C@@H]2[C@@H]([C@@H]([C@H]([C@H](O2)SC)O)O)O)[C@H](C)Cl
• InChI: 1S/C18H33ClN2O5S/c1-5-6-10-7-11(21(3)8-10)17(25)20-12(9(2)19)16-14(23)13(22)15(24)18(26-16)27-4/h9-16,18,22-24H,5-8H2,1-4H3,(H,20,25)/t9-,10+,11-,12+,13-,14+,15+,16+,18+/m0/s1
• InChIKey: KDLRVYVGXIQJDK-AWPVFWJPSA-N
• PubChem CID: 446598
• TTD Drug ID: D0R0ZL
• INTEDE ID: DR0340
• DrugBank ID: DB01190

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

  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: rRNA adenine N-6-methyltransferase ermE (ERME) [1], [2], [3]

• 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 AS19-RrmA-; 562
• In Vitro Model: Escherichia coli DH10B; 316385
• In Vitro Model: Escherichia coli JC7623; 562
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Methylation of specific nucleotides in rRNA is one of the means by which bacteria achieve resistance to macrolides-lincosamides-streptogramin B (MLSB) and ketolide antibiotics.ErmE dimethylation confers high resistance to all the MLSB and ketolide drugs.

Key Molecule: Probable dual-specificity RNA methyltransferase RlmN (RLMN ) [19]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Paenibacillus sp. LC231; 1120679
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: A clindamycin resistance gene relates to the Rlmk 23S ribosomal RNA methyltransferase COG family.Clindamycin targets the peptidyltransferase centre and inhibits protein synthesis by interfering with transfer RNA binding at the A-site.

Key Molecule: Ribosomal RNA large subunit methyltransferase Cfr (CFRB) [20]

• Molecule Alteration: Missense mutation; c.2576G>T
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Staphylococcus aureus ATCC 29213; 1280
• In Vitro Model: Enterococcus faecium ATCC 29212; 1352
• In Vitro Model: Enterococcus faecium ATCC 35667; 1352
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: Cfr methylates the unreactive C2- and C8-carbon atoms on the A2503 residue located in a functionally critical region of the 23S rRNA component.The methylation at C8 protects the Cfr-producing bacteria from the action of five major classes of antibiotics, namely, phenicols, oxazolidinones, pleuromutilins, macrolides, and streptogramin A compounds (PhLOPSA phenotype).

Key Molecule: Carboxymethylenebutenolidase (CLCD) [21]

• 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 ) [22]

• 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) [23]

• 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.

Key Molecule: 23S ribosomal RNA methyltransferase Erm36 (ERM36) [24]

• 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.

Key Molecule: erm(X)cj (Unclear) [8]

• Molecule Alteration: Frameshift mutation; Codon 216 frame shift
• Resistant Disease: Corynebacterium jeikeium infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Corynebacterium glutamicum ATCC 13032; 196627
• In Vitro Model: Staphylococcus aureus ATCC 29213; 1280
• In Vitro Model: Corynebacterium diphtheriae isolate; 1717
• In Vitro Model: Corynebacterium glutamicum kO8; 1718
• In Vitro Model: Corynebacterium jeikeium isolates; 38289
• In Vitro Model: Escherichia coli ATCC 25923; 562
• In Vitro Model: Escherichia coli strain XL1-Blue MRF9; 562
• Experiment for Molecule Alteration: Southern blotting assay
• Experiment for Drug Resistance: Disk diffusion methods assay; agar dilution methods assay
• Mechanism Description: Abundant amplificationproducts of slightly less than 400 bp were generated from DNAisolated from the 17 MLSb-resistant strains, whereas no am-plification products were generated with the DNA isolatedfrom the three susceptible strains. The DNA sequences of the amplification products showed 95% identity to the erm(X) gene isolated from a C. xerosis strain,erm(X)cx or ermCX. Thus, MLSb resistance in C. jeikeiumis associated with the presence of an allele, erm(X)cj, of the class Xermgenes. The first 215 amino acids of the predicted polypeptides for strains CJ12 and CJ21 are 93.5 and 98.6% identical to Erm(X)cx, the Erm protein from C. xerosi. The major difference between the two Erm(X)cj polypeptides and the Erm(X)cx polypeptide is a frame shift within codon 216. This results in the Erm(X)cj polypeptides being 31 amino acids longer than Erm(X)cx.

Key Molecule: ErmR rRNA adenine N6-methyltransferase (ERMR) [16]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Aeromicrobium erythreum infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Aeromicrobium erythreum strains AR18; 2041
• In Vitro Model: Aeromicrobium erythreum strains AR1807; 2041
• In Vitro Model: Aeromicrobium erythreum strains AR1848; 2041
• In Vitro Model: Aeromicrobium erythreum strains AR1849; 2041
• In Vitro Model: Aeromicrobium erythreum strains AR1850; 2041
• In Vitro Model: Aeromicrobium erythreum strains BD170; 2041
• Experiment for Molecule Alteration: Southern blotting assay
• Experiment for Drug Resistance: Disk diffusion assay
• Mechanism Description: Using the Ery- strain AR1807 as a recipient for plasmid-directed integrative recombination, the chromosomal ermR gene (encoding 23S rRNA methyltransferase) was disrupted, ermR-disrupted strains AR1848 and AR1849 were highly sensitive to erythromycin and the other macrolide antibiotics. Phenotypic characterizations demonstrated that ermR is the sole determinant of macrolide antibiotic resistance in A. erythreum. AR18, AR1807, and AR1850 (Ery- Ermr) were resistant to clindamycin, erythromycin, spiramycin, and tylosin (some sensitivity totylosin was observed at high concentrations).

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ABC transporter ATP-binding protein (ABCP) [25], [26]

• 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) [23]

• 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.

Clostridioides difficile intestinal infection [ICD-11: 1A04]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: rRNA adenine N-6-methyltransferase (ErmB) [17]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Clostridium difficile infection [ICD-11: 1A04.0]
• Experimental Note: Discovered Using In-vivo Testing Model
• Mechanism Description: The cellular methylation in C. difficile has been proposed to induce resistance to macrolides (erythromycin, ERY), lincosamide (clindamycin) and streptogramin B antibiotic family. These drugs target at a bacterial 50S ribosomal subunit, causing the inhibition of peptide chain growth by blocking the movement of ribosome. ERY ribosomal methylase B (ErmB) is responsible for ribosomal methylation at the specific site of 23S rRNA, resulting in the prevention of antibiotic binding.

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) [7]

• 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.

Mycobacterial diseases [ICD-11: 1B2Z ]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: 23S ribosomal RNA methyltransferase Erm (ERM39) [10]

• Molecule Alteration: Missense mutation; Putative initiation codon GTG>CTG
• Resistant Disease: Mycobacterium fortuitum infection [ICD-11: 1B2Z.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Mycobacterium peregrinum ATCC14467; 43304
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Mueller-Hinton (MH) broth assay
• Mechanism Description: The erm genes are a diverse collection of methylases that add one or two methyl groups to the adenine at position 2058 (Escherichia coli numbering) of the 23S rRNA; this modification impairs the binding of macrolides to ribosomes, and thus reduces the inhibitory activity of these agents.

Streptococcal pharyngitis [ICD-11: 1B51]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Macrolide-lincosamide-streptogramin B resistance protein (ERMA) [12]

• Molecule Alteration: Methylation; Macrolide-binding site on the ribosome
• Resistant Disease: Streptococcus pyogenes infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli AG100A; 562
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Macrolide resistance commonly occurs due to methylation of the macrolide-binding site on the ribosome by methyltransferases encoded by the erm group of genes, Induction of erm(A) occurs by translational attenuationInduction of erm(A) occurs by translational attenuation.

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) [7]

• 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.

Pasteurellosis [ICD-11: 1B99]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Erm methyltransferase (ERM42) [18]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Pasteurella multocida infection [ICD-11: 1B99.0]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli ATCC 25922; 1322345
• In Vitro Model: Staphylococcus aureus ATCC 29213; 1280
• In Vitro Model: Pasteurella multocida 36950; 1075089
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: The analysis of one representative P. multocida isolate identified an 82 kb integrative and conjugative element (ICE) integrated into the chromosomal DNA. This ICE, designated ICEPmu1, harboured 11 resistance genes, which confer resistance to streptomycin/spectinomycin (aadA25), streptomycin (strA and strB), gentamicin (aadB), kanamycin/neomycin (aphA1), tetracycline [tetR-tet(H)], chloramphenicol/florfenicol (floR), sulphonamides (sul2), tilmicosin/clindamycin [erm(42)] or tilmicosin/tulathromycin [msr(E)-mph(E)].

Bacillus infection [ICD-11: 1C4Y]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: 23S ribosomal RNA methyltransferase Erm34 (ERM34) [6]

• Molecule Alteration: Methylation; Ribosomal methylation
• Resistant Disease: Bacillus clausii infection [ICD-11: 1C4Y.1]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Bacillus clausii ATCC 21536; 79880
• Experiment for Molecule Alteration: Cloning experiments and gene seqencing assay
• Experiment for Drug Resistance: Agar dilution assay
• Mechanism Description: This pattern of resistance generally due to the presence of an erm gene encoding a ribosomal methylase.

Key Molecule: ErmR rRNA adenine N6-methyltransferase (ERMR) [15]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Bacteroides fragilis infection [ICD-11: 1C4Y.6]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Bacteroides distasonis strains; 823
• In Vitro Model: Bacteroides distasonis strains V2002; 823
• In Vitro Model: Bacteroides distasonis strains V2003; 823
• In Vitro Model: Bacteroides distasonis strains V2004; 823
• In Vitro Model: Bacteroides fragilis strain; 817
• In Vitro Model: Bacteroides fragilis strain V503; 817
• In Vitro Model: Bacteroides ovatus strains; 28116
• In Vitro Model: Bacteroides ovatus strains V2008; 28116
• In Vitro Model: Bacteroides thetaiotaomicron strain; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2005; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2006; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2007; 818
• In Vitro Model: Bacteroides uniformis strain; 820
• In Vitro Model: Bacteroides uniformis strain V1760; 820
• In Vitro Model: Bacteroides uniformis strain V1761; 820
• In Vitro Model: Bacteroides uniformis strain V1918; 820
• In Vitro Model: Bacteroides uniformis strain V1921; 820
• In Vitro Model: Bacteroides uniformis strain V2000; 820
• In Vitro Model: Bacteroides uniformis strain V2001; 820
• In Vitro Model: Bacteroides uniformis strain V528; 820
• In Vitro Model: Bacteroides uniformis strain V844; 820
• Experiment for Molecule Alteration: Southern blotting assay
• Mechanism Description: Clindamycin resistance in Bacteroides spp. is usually macrolide-lincosamide-streptogramin B (MLS) resistance conferred by erm genes which are similar to those seen in gram-positive, facultative anaerobes. Of 13 clinical isolates of the Bacteroides group, all were resistant to tetracycline (>10,ug/ml).

Key Molecule: ErmR rRNA adenine N6-methyltransferase (ERMR) [15]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Bacteroides distasonis infection [ICD-11: 1C4Y.5]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Bacteroides distasonis strains; 823
• In Vitro Model: Bacteroides distasonis strains V2002; 823
• In Vitro Model: Bacteroides distasonis strains V2003; 823
• In Vitro Model: Bacteroides distasonis strains V2004; 823
• In Vitro Model: Bacteroides fragilis strain; 817
• In Vitro Model: Bacteroides fragilis strain V503; 817
• In Vitro Model: Bacteroides ovatus strains; 28116
• In Vitro Model: Bacteroides ovatus strains V2008; 28116
• In Vitro Model: Bacteroides thetaiotaomicron strain; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2005; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2006; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2007; 818
• In Vitro Model: Bacteroides uniformis strain; 820
• In Vitro Model: Bacteroides uniformis strain V1760; 820
• In Vitro Model: Bacteroides uniformis strain V1761; 820
• In Vitro Model: Bacteroides uniformis strain V1918; 820
• In Vitro Model: Bacteroides uniformis strain V1921; 820
• In Vitro Model: Bacteroides uniformis strain V2000; 820
• In Vitro Model: Bacteroides uniformis strain V2001; 820
• In Vitro Model: Bacteroides uniformis strain V528; 820
• In Vitro Model: Bacteroides uniformis strain V844; 820
• Experiment for Molecule Alteration: Southern blotting assay
• Mechanism Description: Clindamycin resistance in Bacteroides spp. is usually macrolide-lincosamide-streptogramin B (MLS) resistance conferred by erm genes which are similar to those seen in gram-positive, facultative anaerobes. Of 13 clinical isolates of the Bacteroides group, all were resistant to tetracycline (>10,ug/ml).

Key Molecule: ErmR rRNA adenine N6-methyltransferase (ERMR) [15]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Bacteroides thetaiotaomicron infection [ICD-11: 1C4Y.10]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Bacteroides distasonis strains; 823
• In Vitro Model: Bacteroides distasonis strains V2002; 823
• In Vitro Model: Bacteroides distasonis strains V2003; 823
• In Vitro Model: Bacteroides distasonis strains V2004; 823
• In Vitro Model: Bacteroides fragilis strain; 817
• In Vitro Model: Bacteroides fragilis strain V503; 817
• In Vitro Model: Bacteroides ovatus strains; 28116
• In Vitro Model: Bacteroides ovatus strains V2008; 28116
• In Vitro Model: Bacteroides thetaiotaomicron strain; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2005; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2006; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2007; 818
• In Vitro Model: Bacteroides uniformis strain; 820
• In Vitro Model: Bacteroides uniformis strain V1760; 820
• In Vitro Model: Bacteroides uniformis strain V1761; 820
• In Vitro Model: Bacteroides uniformis strain V1918; 820
• In Vitro Model: Bacteroides uniformis strain V1921; 820
• In Vitro Model: Bacteroides uniformis strain V2000; 820
• In Vitro Model: Bacteroides uniformis strain V2001; 820
• In Vitro Model: Bacteroides uniformis strain V528; 820
• In Vitro Model: Bacteroides uniformis strain V844; 820
• Experiment for Molecule Alteration: Southern blotting assay
• Mechanism Description: Clindamycin resistance in Bacteroides spp. is usually macrolide-lincosamide-streptogramin B (MLS) resistance conferred by erm genes which are similar to those seen in gram-positive, facultative anaerobes. Of 13 clinical isolates of the Bacteroides group, all were resistant to tetracycline (>10,ug/ml).

Key Molecule: ErmR rRNA adenine N6-methyltransferase (ERMR) [15]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Bacteroides ovatus infection [ICD-11: 1C4Y.8]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Bacteroides distasonis strains; 823
• In Vitro Model: Bacteroides distasonis strains V2002; 823
• In Vitro Model: Bacteroides distasonis strains V2003; 823
• In Vitro Model: Bacteroides distasonis strains V2004; 823
• In Vitro Model: Bacteroides fragilis strain; 817
• In Vitro Model: Bacteroides fragilis strain V503; 817
• In Vitro Model: Bacteroides ovatus strains; 28116
• In Vitro Model: Bacteroides ovatus strains V2008; 28116
• In Vitro Model: Bacteroides thetaiotaomicron strain; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2005; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2006; 818
• In Vitro Model: Bacteroides thetaiotaomicron strain V2007; 818
• In Vitro Model: Bacteroides uniformis strain; 820
• In Vitro Model: Bacteroides uniformis strain V1760; 820
• In Vitro Model: Bacteroides uniformis strain V1761; 820
• In Vitro Model: Bacteroides uniformis strain V1918; 820
• In Vitro Model: Bacteroides uniformis strain V1921; 820
• In Vitro Model: Bacteroides uniformis strain V2000; 820
• In Vitro Model: Bacteroides uniformis strain V2001; 820
• In Vitro Model: Bacteroides uniformis strain V528; 820
• In Vitro Model: Bacteroides uniformis strain V844; 820
• Experiment for Molecule Alteration: Southern blotting assay
• Mechanism Description: Clindamycin resistance in Bacteroides spp. is usually macrolide-lincosamide-streptogramin B (MLS) resistance conferred by erm genes which are similar to those seen in gram-positive, facultative anaerobes. Of 13 clinical isolates of the Bacteroides group, all were resistant to tetracycline (>10,ug/ml).

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) [7]

• 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) [7]

• 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) [7]

• 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) [7]

• 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) [7]

• 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) [7]

• 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-22: Injury/poisoning/certain external causes consequences

Surgical wound infection [ICD-11: NE81]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Erythromycin resistance protein (ERM38) [13]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Mycobacterium smegmatis infection [ICD-11: 1B2Z.3]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Mycobacterium smegmatis mc2155; 246196
• In Vitro Model: Mycobacterium smegmatis mc2155/pMIP12; 246196
• In Vitro Model: Mycobacterium smegmatis mc2155/pOMV20; 246196
• In Vitro Model: Mycobacterium smegmatis mc2155/pOMV30; 246196
• Experiment for Molecule Alteration: MALDI mass spectrometry assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: Erm (38) is a specific dimethyltransferase. The strain obtained drug resistance by adding two methyl groups to A2058 in Mycobacterium 23SrRNA.

Key Molecule: Erythromycin resistance protein (ERM38) [13]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Mycobacterium smegmatis infection [ICD-11: 1B2Z.3]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Mycobacterium smegmatis mc2155; 246196
• In Vitro Model: Mycobacterium smegmatis mc2155/pMIP12; 246196
• In Vitro Model: Mycobacterium smegmatis mc2155/pOMV20; 246196
• In Vitro Model: Mycobacterium smegmatis mc2155/pOMV30; 246196
• Experiment for Molecule Alteration: MALDI mass spectrometry assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: Erm (38) is a specific dimethyltransferase. The strain obtained drug resistance by adding two methyl groups to A2058 in Mycobacterium 23SrRNA.

References

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