Drug Information

Drug (ID: DG00310) and It's Reported Resistant Information

• Name: Kanamycin
• Synonyms: Aspidium; KAN; Kanamicina; Kanamycine; Kanamycinum; Kantrex; Klebcil; KANAMYCIN A; Kanamicina [Italian]; Kanamycin A tetracation; Kanamycin Base; Kanamycin monosulfate; Kanamycin sulfate; Kenamycin A; Liposomal Kanamycin; KM (the Antibiotic); Kanamycin [INN:BAN]; Kanamycin monosulfate (JP15); Kanamycinsulfate (JP15); Kanamycin sulfate (TN); Kanamycin sulfate (USP); Kanamycine [INN-French]; Kanamycinum [INN-Latin]; Kantrex (TN); Kantrex (1:1 sulfate); Klebcil (1:1 sulfate); O-3-amino-3-deoxy-alpha-D-glucopyranosyl-(1->6)-O-(6-amino-6-deoxy-alpha-D-glucopyranosyl-(1->4))-2-deoxy-D-streptamine; O-3-Amino-3-deoxy-.alpha.-D-glucopyranosyl-(1->6)-O-[6-amino-6-deoxy-.alpha.-D-glucopyranosyl-(1->4)]-2-deoxy-D-streptamine; (1S,2R,3R,4S,6R)-4,6-diamino-3-(6-amino-6-deoxy-alpha-D-glucopyranosyloxy)-2-hydroxycyclohexyl 3-amino-3-deoxy-alpha-D-glucopyranoside; (1S,2R,3R,4S,6R)-4,6-diamino-3-[(6-amino-6-deoxy-alpha-D-glucopyranosyl)oxy]-2-hydroxycyclohexyl 3-amino-3-deoxy-alpha-D-glucopyranoside; (1S,2R,3R,4S,6R)-4,6-diazaniumyl-3-(6-azaniumyl-6-deoxy-alpha-D-glucopyranosyloxy)-2-hydroxycyclohexyl 3-azaniumyl-3-deoxy-alpha-D-glucopyranoside; (2R,3S,4S,5R,6R)-2-(aminomethyl)-6-[(1R,2R,3S,4R,6S)-4,6-diamino-3-[(2S,3R,4S,5S,6R)-4-amino-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-2-hydroxycyclohexyl]oxyoxane-3,4,5-triol; 4,6-Diamino-2-hydroxy-1,3-cyclohexane 3,6'diamino-3,6'-dideoxydi-alpha-D-glucoside; 4,6-diamino-2-hydroxy-1,3-cyclohexylene 3,6'-diamino-3,6'-dideoxydi-D-glucopyranoside
• Indication:
  In total 1 Indication(s)
  Bacterial infection [ICD-11: 1A00-1C4Z]; Approved; [1], [2]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (16 diseases)
  Bacteremia [ICD-11: MA15]; [3]
  Bacterial genitourinary infection [ICD-11: GA0Z-GC8Z]; [4]
  Bacterial infection [ICD-11: 1A00-1C4Z]; [5]
  Campylobacteriosis [ICD-11: 1C40]; [6]
  Escherichia coli intestinal infection [ICD-11: 1A03]; [7]
  Gram-negative bacterial infection [ICD-11: 1B74-1G40]; [4]
  Infective endocarditis [ICD-11: BB40]; [3]
  Mycobacterial diseases [ICD-11: 1B2Z ]; [8]
  Non-tuberculous mycobacteria infection [ICD-11: 1B21]; [3]
  Peritonitis [ICD-11: DC50]; [4]
  Pneumonia [ICD-11: CA40]; [9]
  Respiratory trac infection [ICD-11: CA45]; [4]
  Sepsis [ICD-11: 1G40]; [4]
  Serious necrotizing pneumonia [ICD-11: CA43]; [3]
  Surgical wound infection [ICD-11: NE81]; [3]
  Toxic shock syndrome [ICD-11: 1C45]; [3]
  Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (5 diseases)
  Actinomycetoma [ICD-11: 1C43]; [10]
  Bacterial infection [ICD-11: 1A00-1C4Z]; [1], [2]
  Escherichia coli intestinal infection [ICD-11: 1A03]; [11]
  Gram-negative bacterial infection [ICD-11: 1B74-1G40]; [12]
  Pasteurellosis [ICD-11: 1B99]; [13]
• Target: Staphylococcus 30S ribosomal subunit (Stap-coc pbp2); F4NA87_STAAU; [1]
• Formula: C18H36N4O11
• IsoSMILES: C1[C@H]([C@@H]([C@H]([C@@H]([C@H]1N)O[C@@H]2[C@@H]([C@H]([C@@H]([C@H](O2)CN)O)O)O)O)O[C@@H]3[C@@H]([C@H]([C@@H]([C@H](O3)CO)O)N)O)N
• InChI: 1S/C18H36N4O11/c19-2-6-10(25)12(27)13(28)18(30-6)33-16-5(21)1-4(20)15(14(16)29)32-17-11(26)8(22)9(24)7(3-23)31-17/h4-18,23-29H,1-3,19-22H2/t4-,5+,6-,7-,8+,9-,10-,11-,12+,13-,14-,15+,16-,17-,18-/m1/s1
• InChIKey: SBUJHOSQTJFQJX-NOAMYHISSA-N
• PubChem CID: 6032
• ChEBI ID: CHEBI:17630
• TTD Drug ID: D0YV1Q
• INTEDE ID: DR2175
• DrugBank ID: DB01172

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 methyltransferase PikR1 (PIKR1) [1], [2]

• 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; 668369
• In Vitro Model: Escherichia coli BL21(DE3); 469008
• In Vitro Model: Escherichia coli BL21(DE3)pLysS; 866768
• In Vitro Model: Escherichia coli S17-1; 1227813
• In Vitro Model: Streptomyces antibioticus ATCC 11891; 1890
• In Vitro Model: Streptomyces venezuelae ATCC 15439; 54571
• Experiment for Molecule Alteration: Whole genome sequence assay
• Mechanism Description: Modification of 23S rRNA, which is the target site for methymycin and its derivatives, by PikR1 and PikR2 is a primary self-resistance mechanism.

Key Molecule: rRNA methyltransferase PikR2 (PIKR2) [1], [2]

• 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; 668369
• In Vitro Model: Escherichia coli BL21(DE3); 469008
• In Vitro Model: Escherichia coli BL21(DE3)pLysS; 866768
• In Vitro Model: Escherichia coli S17-1; 1227813
• In Vitro Model: Streptomyces antibioticus ATCC 11891; 1890
• In Vitro Model: Streptomyces venezuelae ATCC 15439; 54571
• Experiment for Molecule Alteration: Whole genome sequence assay
• Mechanism Description: Modification of 23S rRNA, which is the target site for methymycin and its derivatives, by PikR1 and PikR2 is a primary self-resistance mechanism.

Key Molecule: 16S rRNA (guanine(1405)-N(7))-methyltransferase (RMTA) [14]

• Molecule Alteration: Methylation; p.M7G1405
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli BL21(DE3); 469008
• Experiment for Molecule Alteration: Protein-RNA footprinting assay
• Experiment for Drug Resistance: Isothermal titration calorimetry assay
• Mechanism Description: Sgm methylates G1405 in 16S rRNA to m7G, thereby rendering the ribosome resistant to 4, 6-disubstituted deoxystreptamine aminoglycosides.

Key Molecule: 16S rRNA (adenine(1408)-N(1))-methyltransferase (KAMB) [15], [16]

• 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 BL21(DE3); 469008
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: The 16S ribosomal RNA methyltransferase enzymes that modify nucleosides in the drug binding site to provide self-resistance in aminoglycoside-producing micro-organisms have been proposed to comprise two distinct groups of S-adenosyl-l-methionine (SAM)-dependent RNA enzymes, namely the kgm and kam families.

Key Molecule: 16S rRNA (guanine(1405)-N(7))-methyltransferase (RMTA) [17]

• Molecule Alteration: Expression; Intergeneric lateral gene transfer
• Resistant Disease: Pseudomonas aeruginosa infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pseudomonas aeruginosa AR-2; 287
• Experiment for Molecule Alteration: PCR screening assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: The 16S rRNA methylase gene has undergone intergeneric horizontal gene transfer from some aminoglycoside producing microorganisms to Pseudomonas aeruginosa, which is called rmtA. rmtA protect bacterial 16S rRNA from intrinsic aminoglycosides by methylation.

Key Molecule: erm(X)cj (Unclear) [5]

• 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.

Drug Inactivation by Structure Modification (DISM)

Key Molecule: AacA43 aminoglycoside (AACA43) [18]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Klebsiella pneumoniae LT12; 573
• In Vitro Model: Klebsiella pneumoniae SSI2.46; 573
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Like related aminoglycoside-(6')-acetyltransferases, AacA43 confers clinically relevant resistance to kanamycin, tobramycin, and some less-used aminoglycosides but not to gentamicin.

Key Molecule: Aminoglycoside N(6')-acetyltransferase type 1 (A6AC1) [19]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pseudomonas aeruginosa PAO1; 208964
• In Vitro Model: Pseudomonas aeruginosa Nk0001; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0002; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0003; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0004; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0005; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0006; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0007; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0008; 287
• In Vitro Model: Pseudomonas aeruginosa Nk0009; 287
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Micro-dilution method assay
• Mechanism Description: Recombinant AAC(6')-Iag protein showed aminoglycoside 6'-N-acetyltransferase activity using thin-layer chromatography (TLC) and MS spectrometric analysis. Escherichia coli carrying aac(6')-Iag showed resistance to amikacin, arbekacin, dibekacin, isepamicin, kanamycin, sisomicin, and tobramycin; but not to gentamicin.AAC(6')-Iag is a functional acetyltransferase that modifies alternate amino groups on the AGs.

Key Molecule: Aminoglycoside 3'-phosphotransferase (A3AP) [20]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Stenotrophomonas maltophilia infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli; 668369
• Experiment for Molecule Alteration: PCR amplification assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: Aph(3')-IIc significantly increases MICs of kanamycin, neomycin, butirosin, and paromomycin when expressed in Escherichia coli. Disruption of aph(3')-IIc results in decreased MICs of these drugs.

Key Molecule: AAC(6')-Ib family aminoglycoside 6'-N-acetyltransferase (AAC6IB) [21]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Pseudomonas aeruginosa infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli DH10B; 316385
• In Vitro Model: Escherichia coli HB101; 634468
• In Vitro Model: Pseudomonas aeruginosa ATCC 27853; 287
• In Vitro Model: Escherichia coli JM109; 562
• In Vitro Model: Escherichia coli k-12; 83333
• In Vitro Model: Pseudomonas aeruginosa Pa695; 287
• Experiment for Molecule Alteration: PCR experiments assay
• Experiment for Drug Resistance: Disk diffusion method assay
• Mechanism Description: The fusion product was functional, as was the product of each gene cloned separately: AAC(3)-I, despite the deletion of the four last amino acids, and AAC(6"), which carried three amino acid changes compared with the most homologous sequence. The AAC(3)-I protein conferred an expected gentamicin and fortimicin resistance, and the AAC(6"), despite the Leu-119-Ser substitution, yielded resistance to kanamycin, tobramycin, and dibekacin, but slightly affected netilmicin and amikacin, and had no apparent effect on gentamicin. The fusion product conveyed a large profile of resistance, combining the AAC(6") activity with a higher level of gentamicin resistance without accompanying fortimicin resistance.

Key Molecule: Aminoglycoside 3'-phosphotransferase (A3AP) [22]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Streptococcus faecalis infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli strain JM 10; 562
• In Vitro Model: Escherichia coli strain k802; 562
• In Vitro Model: Streptococcus faecnlis strain JHZ-15; 1351
• Experiment for Molecule Alteration: Chemical sequencing method assay
• Experiment for Drug Resistance: Disc sensitivity tests assay
• Mechanism Description: Streptococcus jaecalis strain JH2- 15 is resistant to high levels of kanamycin (MIC > 1 mg/ml) and structurally related antibiotics. This broad-resistance phenotype is due to the presence of an APH-III. The gene encoding the enzyme in JH2-15 is borne by a 72.6-kb R plasmid, pJH1, capable of self-transfer to streptococcal cells. In pathogenic bacteria, 3'-aminoglycoside phosphotransferases exist under three (types I, II, and III) isozymic forms which differ, in particular, in their substrate ranges. APH-III enzyme appears to be specific for the Gram-positive cocci, whereas 3'-phosphotransferases of types I and II are found exclusively in Gram-negative bacteria.

Key Molecule: Aminoglycoside 3'-phosphotransferase (A3AP) [23]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Serratia marcescens infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli C41(DE3); 469008
• In Vitro Model: Escherichia coli DH5alpha; 668369
• In Vitro Model: Escherichia coli Ecmrs144; 562
• In Vitro Model: Escherichia coli Ecmrs150; 562
• In Vitro Model: Escherichia coli Ecmrs151; 562
• In Vitro Model: Escherichia coli strain 83-125; 562
• In Vitro Model: Escherichia coli strain 83-75; 562
• In Vitro Model: Escherichia coli strain JM83; 562
• In Vitro Model: Escherichia coli strain JM83(pRPG101); 562
• In Vitro Model: Escherichia coli strain M8820Mu; 562
• In Vitro Model: Escherichia coli strain MC1065; 562
• In Vitro Model: Escherichia coli strain MC1065(pRPG101); 562
• In Vitro Model: Escherichia coli strain POII1681; 562
• In Vitro Model: Escherichia coli strain PRC930(pAO43::Tn9O3); 562
• In Vitro Model: Klebsiella pneumoniae strains; 573
• In Vitro Model: Serratia marcescens strains; 615
• Experiment for Molecule Alteration: Restriction enzyme treating assay
• Experiment for Drug Resistance: Cation-supplemented Mueller-Hinton broth assay; agar dilution with MH agar assay
• Mechanism Description: Clinical isolates of Klebsiella pneumoniae and Serratia marcescens at a hospital that had used amikacin as its principal aminoglycoside for the preceding 42 months demonstrated high-level resistance to amikacin (greater than or equal to 256 micrograms/ml), kanamycin (greater than or equal to 256 micrograms/ml), gentamicin (greater than or equal to 64 micrograms/ml), netilmicin (64 micrograms/ml), and tobramycin (greater than or equal to 16 micrograms/ml). The clinical isolates and transformants produced a novel 3'-phosphotransferase, APH(3'), that modified amikacin and kanamycin in vitro.

Escherichia coli intestinal infection [ICD-11: 1A03]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Aminoglycoside acetyltransferase (AAC) [24]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Escherichia coli infection [ICD-11: 1A03.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli DH5alpha; 668369
• In Vitro Model: Escherichia coli SCH92111602; 562
• Experiment for Molecule Alteration: Dot blot hybridizations assay
• Experiment for Drug Resistance: Standard broth microdilution method assay
• Mechanism Description: Escherichia coli SCH92111602 expresses an aminoglycoside resistance profile similar to that conferred by the aac(6')-Ie-aph(2")-Ia gene found in gram-positive cocci and was found to contain the aminoglycoside resistance genes aph(2")-Ib and aac(6')-Im (only 44 nucleotides apart). SCH92111602 is an Escherichia coli clinical isolate resistant to a number of aminoglycoside antibiotics, including gentamicin, tobramycin, and amikacin, and contains an approximately 50-kb plasmid.

Key Molecule: Aminoglycoside acetyltransferase (AAC) [24]

• Molecule Alteration: Expression; Acquired
• Resistant Disease: Escherichia coli infection [ICD-11: 1A03.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli DH5alpha; 668369
• In Vitro Model: Escherichia coli SCH92111602; 562
• Experiment for Molecule Alteration: Dot blot hybridizations assay
• Experiment for Drug Resistance: Standard broth microdilution method assay
• Mechanism Description: Plasmid DNA isolated from this strain was introduced into Escherichia coli DH5alpha by transformation, and colonies were selected on Luria-Bertani agar plates containing 10 ug of tobramycin per ml. Analysis of restriction digests on agarose gels of DNA from a tobramycin-resistant transformant confirmed the presence of the same 50-kb plasmid that was isolated from Escherichia coli SCH92111602.

Key Molecule: Acetylpolyamine amidohydrolase (APAH) [7]

• Molecule Alteration: Expression; Acquired
• Resistant Disease: Escherichia coli infection [ICD-11: 1A03.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli; 668369
• In Vitro Model: Achromobacter xylosoxydans subsp. denitrificans AX-22; 85698
• In Vitro Model: Escherichia coli MkD-135; 562
• In Vitro Model: Pseudomonas aeruginosa 10145/3; 287
• Experiment for Molecule Alteration: DNA extraction and Sequencing assay
• Experiment for Drug Resistance: Macrodilution broth method assay
• Mechanism Description: The aphA15 gene is the first example of an aph-like gene carried on a mobile gene cassette, and its product exhibits close similarity to the APH(3')-IIa aminoglycoside phosphotransferase encoded by Tn5 (36% amino acid identity) and to an APH(3')-IIb enzyme from Pseudomonas aeruginosa (38% amino acid identity). Expression of the cloned aphA15 gene in Escherichia coli reduced the susceptibility to kanamycin and neomycin as well as (slightly) to amikacin, netilmicin, and streptomycin.

Key Molecule: Aminoglycoside 3'-phosphotransferase (A3AP) [23]

• Molecule Alteration: Expression; Acquired
• Resistant Disease: Escherichia coli infection [ICD-11: 1A03.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli C41(DE3); 469008
• In Vitro Model: Escherichia coli DH5alpha; 668369
• In Vitro Model: Escherichia coli Ecmrs144; 562
• In Vitro Model: Escherichia coli Ecmrs150; 562
• In Vitro Model: Escherichia coli Ecmrs151; 562
• In Vitro Model: Escherichia coli strain 83-125; 562
• In Vitro Model: Escherichia coli strain 83-75; 562
• In Vitro Model: Escherichia coli strain JM83; 562
• In Vitro Model: Escherichia coli strain JM83(pRPG101); 562
• In Vitro Model: Escherichia coli strain M8820Mu; 562
• In Vitro Model: Escherichia coli strain MC1065; 562
• In Vitro Model: Escherichia coli strain MC1065(pRPG101); 562
• In Vitro Model: Escherichia coli strain POII1681; 562
• In Vitro Model: Escherichia coli strain PRC930(pAO43::Tn9O3); 562
• In Vitro Model: Klebsiella pneumoniae strains; 573
• In Vitro Model: Serratia marcescens strains; 615
• Experiment for Molecule Alteration: Restriction enzyme treating assay
• Experiment for Drug Resistance: Cation-supplemented Mueller-Hinton broth assay; agar dilution with MH agar assay
• Mechanism Description: The resistant strains contained an identical 6.8-kilobase plasmid, pRPG101. Transformation of pRPG101 into Escherichia coli produced high-level resistance to amikacin (greater than or equal to 256 micrograms/ml) and kanamycin (greater than or equal to 256 micrograms/ml) but unchanged susceptibilities to gentamicin, netilmicin, and tobramycin. The clinical isolates and transformants produced a novel 3'-phosphotransferase, APH(3'), that modified amikacin and kanamycin in vitro.

Key Molecule: Aminoglycoside 3'-phosphotransferase (A3AP) [25]

• Molecule Alteration: Expression; Acquired
• Resistant Disease: Escherichia coli infection [ICD-11: 1A03.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli strain HB101; 634468
• In Vitro Model: Acinetobacter baumannii strain BM2580; 470
• In Vitro Model: Bacillus subtilis strain BS168; 1423
• Experiment for Molecule Alteration: SDS-PAGE assay
• Mechanism Description: Resistance to aminogiycosides in Aeinetobaeter is widespread and is mainly the result of the production of enzymes which modify the antibiotics. The enzymes beiong to three ciasses: phosphotransferases (APH), acetyltransferases (AAC). A. baumahnii strain BM2580, a representative of one of these epidemics, was shown to synthesize a 3'-aminoglycoside phosphotransferase. Substrate specificity and DNA annealing studies indicated that the isozyme in A. baumannii was of a new type, designated APH(3')-VI. Cloning and localization of the kanamyein-resistance determinant Piasmids pAT235 and pAT236, constructed by inserting the 1.8kb Ace\ and 2.1 kb EcoRI fragments of plP1841, respectively, into pUC18, conferred kanamycin resistance to E. coli.

Key Molecule: kanamycin resistance protein Kmr (KMR) [11]

• Molecule Alteration: Expression; Acquired
• Resistant Disease: Escherichia coli infection [ICD-11: 1A03.0]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli strain HB101; 634468
• In Vitro Model: Escherichia coli strain JM 105; 562
• Experiment for Molecule Alteration: Dideoxy chain-termination method assay
• Experiment for Drug Resistance: Disk diffusion method assay
• Mechanism Description: The kanamycin resistance determinant of the broad-host-range plasmid RP4 encodes an aminoglycoside 3'-phosphotransferase of type I. The nucleotide sequence of the kanamycin resistance gene (kmr) and the right end of the insertion element IS8 of plasmid RP4 has been determined. The nucleotide sequence has been compared to five related aphA genes originating from gram-negative and gram-positive organisms and from antibiotic producers. Among these that of Tn903 shares the highest degree of similarity (60%) with the RP4 gene. Significant similarities were also detected between the amino acid sequences of the six enzymes.

Key Molecule: Aminoglycoside 3'-phosphotransferase (A3AP) [6]

• Molecule Alteration: Expression; Acquired
• Resistant Disease: Escherichia coli infection [ICD-11: 1A03.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Campylobacter jejuni; 197
• In Vitro Model: Escherichia coli strain JC2926 C600; 562
• Experiment for Molecule Alteration: Dideoxy method assay
• Experiment for Drug Resistance: Disk diffusion method assay
• Mechanism Description: A novel kanamycin phosphotransferase gene, aphA-7, was cloned from a 14-kb plasmid obtained from a strain of Campylobacter jejuni and the nucleotide sequence of the gene was determined. The presumed open reading frame of the aphA-7 structural gene was 753 bp in length and encoded a protein of 251 amino acids with a calculated weight of 29,691 Da.

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: Lincomycin resistance efflux pump (LMRS) [3]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Superficial skin infection by Staphylococcus aureus infection [ICD-11: 1B21.3]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli kAM32; 562
• In Vitro Model: Staphylococcus aureus OM505; 1280
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: LmrS is a multidrug efflux pump of the major facilitator superfamily from staphylococcus aureus.

Mycobacterial diseases [ICD-11: 1B2Z ]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Aminoglycoside 2'-N-acetyltransferase (A2NA) [8]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Mycobacterium fortuitum infection [ICD-11: 1B2Z.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli XL1-Blue; 562
• In Vitro Model: Streptomyces lividans strain 1326; 1200984
• In Vitro Model: Mycolicibacterium fortuitum strain FC1k; 1766
• In Vitro Model: Mycolicibacterium smegmatis strain mc2 155; 246196
• Experiment for Molecule Alteration: Southern blot hybridizations assay
• Experiment for Drug Resistance: Twofold dilution of antibiotics assay
• Mechanism Description: Thirty-four environmental and clinical isolates belonging to theM. fortuitumcomplex were chosen for the present study. The MICs of gentamicin varied, ranging from 2 to 16mg/ml. Crude extracts of all 34 strains were shown to have AAC activity. Acetylation of gentamicin, tobramycin, and kanamycins A and B was found for all the strains, showing a substrate profile consistent with the presence of an AAC(3) activity. Environmental isolateM. fortuitumFC1k was chosen for further studies because of its high level of AAC activity and the level of resistance to gentamicin (MIC, 16mg/ml).

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

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Bifunctional AAC/APH (AAC/APH) [4]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Gram-negative pathogens infection [ICD-11: 1B74-1G40]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli BL21(DE3); 469008
• In Vitro Model: Escherichia coli JM83; 562
• Experiment for Molecule Alteration: SDS-PAGE assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Aminoglycoside 2"-phosphotransferases are the major aminoglycoside-modifying enzymes in clinical isolates of enterococci and staphylococci.APH(2")-If. This enzyme confers resistance to the 4,6-disubstituted aminoglycosides kanamycin, tobramycin, dibekacin, gentamicin, and sisomicin, but not to arbekacin, amikacin, isepamicin, or netilmicin.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: MipA/OmpV family protein (MIPA) [12]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: Gram-negative bacterial infection [ICD-11: 1B74-1G40]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli k-12 BW25113; 679895
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: OM proteins, a unique OM component of Gram-negative bacteria, constitute a barrier against large hydrophilic and lipophilic molecules and therefore play an important role in stress responses to drugs, osmotic pressure and acids.MipA is a novel OM protein related to antibiotic resistance.

Pasteurellosis [ICD-11: 1B99]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Acetylpolyamine amidohydrolase (APAH) [13]

• 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)].

Campylobacteriosis [ICD-11: 1C40]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Aminoglycoside 3'-phosphotransferase (A3AP) [6]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Campylobacter fetus infection [ICD-11: 1C40.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Campylobacter jejuni; 197
• In Vitro Model: Escherichia coli strain JC2926 C600; 562
• Experiment for Molecule Alteration: Dideoxy method assay
• Experiment for Drug Resistance: Disk diffusion method assay
• Mechanism Description: A novel kanamycin phosphotransferase gene, aphA-7, was cloned from a 14-kb plasmid obtained from a strain of Campylobacter jejuni and the nucleotide sequence of the gene was determined. The presumed open reading frame of the aphA-7 structural gene was 753 bp in length and encoded a protein of 251 amino acids with a calculated weight of 29,691 Da.

Actinomycetoma [ICD-11: 1C43]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Aminoglycoside N(3)-acetyltransferase (A3AC) [10]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Streptomyces griseus infection [ICD-11: 1C43.7]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Streptomyces griseus strain SS-1198; 1911
• In Vitro Model: Streptomyces lividans strain Tk21; 1916
• In Vitro Model: Streptomyces lividans strain pIJ702; 1916
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: Maximum growth allowance concentrations assay
• Mechanism Description: We determined the molecular basis for the enhanced expression of the aac(3)-Xa gene encoding an aminoglycoside 3-N-acetyltransferase in Streptomyces griseus. A C-->T substitution was identified at the putative promoter of the mutant gene. RNA analyses demonstrated that the substitution caused a marked increase in the production of the gene-specific transcripts. Therefore, it seemed very likely that the aac(3)-Xa gene was activated by the substitution resulting in the emergence of a stronger promoter.

Key Molecule: Aminoglycoside N(3)-acetyltransferase (A3AC) [10]

• Molecule Alteration: Expression; Acquired
• Resistant Disease: Streptomyces lividans infection [ICD-11: 1C43.8]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Streptomyces griseus strain SS-1198; 1911
• In Vitro Model: Streptomyces lividans strain Tk21; 1916
• In Vitro Model: Streptomyces lividans strain pIJ702; 1916
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: Maximum growth allowance concentrations assay
• Mechanism Description: After the insertion of these fragments into pIJ702 with all possible combinations, the hybrid genes were tested for their ability to confer km resistance to S. lividans Tk21. A high level (1,000 ug/ml) of km resistance was obtained only with genes containing the 0.5-kb BglII-BamHI fragment derived from the mutant gene. By contrast, genes containing the 0.5-kb fragment from the wild-type gene conferred resistance to km at concentrations as low as 50 ug/ml.

Toxic shock syndrome [ICD-11: 1C45]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Lincomycin resistance efflux pump (LMRS) [3]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli kAM32; 562
• In Vitro Model: Staphylococcus aureus OM505; 1280
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: LmrS is a multidrug efflux pump of the major facilitator superfamily from staphylococcus aureus.

Sepsis [ICD-11: 1G40]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Bifunctional AAC/APH (AAC/APH) [4]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Sepsis [ICD-11: 1G40.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli BL21(DE3); 469008
• In Vitro Model: Escherichia coli JM83; 562
• Experiment for Molecule Alteration: SDS-PAGE assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Aminoglycoside 2"-phosphotransferases are the major aminoglycoside-modifying enzymes in clinical isolates of enterococci and staphylococci.APH(2")-If. This enzyme confers resistance to the 4,6-disubstituted aminoglycosides kanamycin, tobramycin, dibekacin, gentamicin, and sisomicin, but not to arbekacin, amikacin, isepamicin, or netilmicin.

ICD-11: Circulatory system diseases

Infective endocarditis [ICD-11: BB40]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Bifunctional AAC/APH (AAC/APH) [4]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Infective endocarditis [ICD-11: BB40.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli BL21(DE3); 469008
• In Vitro Model: Escherichia coli JM83; 562
• Experiment for Molecule Alteration: SDS-PAGE assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Aminoglycoside 2"-phosphotransferases are the major aminoglycoside-modifying enzymes in clinical isolates of enterococci and staphylococci.APH(2")-If. This enzyme confers resistance to the 4,6-disubstituted aminoglycosides kanamycin, tobramycin, dibekacin, gentamicin, and sisomicin, but not to arbekacin, amikacin, isepamicin, or netilmicin.

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Lincomycin resistance efflux pump (LMRS) [3]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli kAM32; 562
• In Vitro Model: Staphylococcus aureus OM505; 1280
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: LmrS is a multidrug efflux pump of the major facilitator superfamily from staphylococcus aureus.

ICD-12: Respiratory system diseases

Pneumonia [ICD-11: CA40]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Aminoglycoside 3'-phosphotransferase (A3AP) [23]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Klebsiella pneumoniae infection [ICD-11: CA40.1]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli C41(DE3); 469008
• In Vitro Model: Escherichia coli DH5alpha; 668369
• In Vitro Model: Escherichia coli Ecmrs144; 562
• In Vitro Model: Escherichia coli Ecmrs150; 562
• In Vitro Model: Escherichia coli Ecmrs151; 562
• In Vitro Model: Escherichia coli strain 83-125; 562
• In Vitro Model: Escherichia coli strain 83-75; 562
• In Vitro Model: Escherichia coli strain JM83; 562
• In Vitro Model: Escherichia coli strain JM83(pRPG101); 562
• In Vitro Model: Escherichia coli strain M8820Mu; 562
• In Vitro Model: Escherichia coli strain MC1065; 562
• In Vitro Model: Escherichia coli strain MC1065(pRPG101); 562
• In Vitro Model: Escherichia coli strain POII1681; 562
• In Vitro Model: Escherichia coli strain PRC930(pAO43::Tn9O3); 562
• In Vitro Model: Klebsiella pneumoniae strains; 573
• In Vitro Model: Serratia marcescens strains; 615
• Experiment for Molecule Alteration: Restriction enzyme treating assay
• Experiment for Drug Resistance: Cation-supplemented Mueller-Hinton broth assay; agar dilution with MH agar assay
• Mechanism Description: Clinical isolates of Klebsiella pneumoniae and Serratia marcescens at a hospital that had used amikacin as its principal aminoglycoside for the preceding 42 months demonstrated high-level resistance to amikacin (greater than or equal to 256 micrograms/ml), kanamycin (greater than or equal to 256 micrograms/ml), gentamicin (greater than or equal to 64 micrograms/ml), netilmicin (64 micrograms/ml), and tobramycin (greater than or equal to 16 micrograms/ml). The clinical isolates and transformants produced a novel 3'-phosphotransferase, APH(3'), that modified amikacin and kanamycin in vitro.

Key Molecule: Aminoglycoside 3'-phosphotransferase (A3AP) [25]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Acinetobacter baumannii infection [ICD-11: CA40.4]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli strain HB101; 634468
• In Vitro Model: Acinetobacter baumannii strain BM2580; 470
• In Vitro Model: Bacillus subtilis strain BS168; 1423
• Experiment for Molecule Alteration: Amino acid sequence comparison assay
• Mechanism Description: Resistance to aminogiycosides in Aeinetobaeter is widespread and is mainly the result of the production of enzymes which modify the antibiotics. The enzymes beiong to three ciasses: phosphotransferases (APH), acetyltransferases (AAC). A. baumahnii strain BM2580, a representative of one of these epidemics, was shown to synthesize a 3'-aminoglycoside phosphotransferase. Substrate specificity and DNA annealing studies indicated that the isozyme in A. baumannii was of a new type, designated APH(3')-VI.

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: MATE family efflux transporter (ABEM) [9]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Acinetobacter baumannii infection [ICD-11: CA40.4]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli kAM32; 562
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: AbeM was found to be an H+-coupled multidrug efflux pump and a unique member of the MATE family which lead to drug resistance.

Serious necrotizing pneumonia [ICD-11: CA43]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Lincomycin resistance efflux pump (LMRS) [3]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli kAM32; 562
• In Vitro Model: Staphylococcus aureus OM505; 1280
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: LmrS is a multidrug efflux pump of the major facilitator superfamily from staphylococcus aureus.

Respiratory trac infection [ICD-11: CA45]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Bifunctional AAC/APH (AAC/APH) [4]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Respiratory trac infection [ICD-11: CA45.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli BL21(DE3); 469008
• In Vitro Model: Escherichia coli JM83; 562
• Experiment for Molecule Alteration: SDS-PAGE assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Aminoglycoside 2"-phosphotransferases are the major aminoglycoside-modifying enzymes in clinical isolates of enterococci and staphylococci.APH(2")-If. This enzyme confers resistance to the 4,6-disubstituted aminoglycosides kanamycin, tobramycin, dibekacin, gentamicin, and sisomicin, but not to arbekacin, amikacin, isepamicin, or netilmicin.

ICD-13: Digestive system diseases

Peritonitis [ICD-11: DC50]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Bifunctional AAC/APH (AAC/APH) [4]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Gram-negative pathogens infection [ICD-11: 1B74-1G40]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli BL21(DE3); 469008
• In Vitro Model: Escherichia coli JM83; 562
• Experiment for Molecule Alteration: SDS-PAGE assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Aminoglycoside 2"-phosphotransferases are the major aminoglycoside-modifying enzymes in clinical isolates of enterococci and staphylococci.APH(2")-If. This enzyme confers resistance to the 4,6-disubstituted aminoglycosides kanamycin, tobramycin, dibekacin, gentamicin, and sisomicin, but not to arbekacin, amikacin, isepamicin, or netilmicin.

ICD-16: Genitourinary system diseases

Bacterial genitourinary infection [ICD-11: GA0Z-GC8Z]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Bifunctional AAC/APH (AAC/APH) [4]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Gram-negative pathogens infection [ICD-11: 1B74-1G40]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli BL21(DE3); 469008
• In Vitro Model: Escherichia coli JM83; 562
• Experiment for Molecule Alteration: SDS-PAGE assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Aminoglycoside 2"-phosphotransferases are the major aminoglycoside-modifying enzymes in clinical isolates of enterococci and staphylococci.APH(2")-If. This enzyme confers resistance to the 4,6-disubstituted aminoglycosides kanamycin, tobramycin, dibekacin, gentamicin, and sisomicin, but not to arbekacin, amikacin, isepamicin, or netilmicin.

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: Lincomycin resistance efflux pump (LMRS) [3]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli kAM32; 562
• In Vitro Model: Staphylococcus aureus OM505; 1280
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: LmrS is a multidrug efflux pump of the major facilitator superfamily from staphylococcus aureus.

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

Surgical wound infection [ICD-11: NE81]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Lincomycin resistance efflux pump (LMRS) [3]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Staphylococcus aureus infection [ICD-11: 1B54.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli kAM32; 562
• In Vitro Model: Staphylococcus aureus OM505; 1280
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: LmrS is a multidrug efflux pump of the major facilitator superfamily from staphylococcus aureus.

References

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• Ref 23: Isolation, characterization, and cloning of a plasmid-borne gene encoding a phosphotransferase that confers high-level amikacin resistance in enteric bacilli. Antimicrob Agents Chemother. 1988 Sep;32(9):1379-84. doi: 10.1128/AAC.32.9.1379.
• Ref 24: Aminoglycoside resistance genes aph(2")-Ib and aac(6')-Im detected together in strains of both Escherichia coli and Enterococcus faecium. Antimicrob Agents Chemother. 2001 Oct;45(10):2691-4. doi: 10.1128/AAC.45.10.2691-2694.2001.
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