Drug (ID: DG00301) and It's Reported Resistant Information
Name
Amikacin
Synonyms
Amicacin; Amikacina; Amikacine; Amikacinum; Amikavet; Amikin; Arikace; Briclin; Kaminax; Lukadin; Mikavir; AMIKACIN SULFATE; Amikacin Base; Amikacin Dihydrate; ANTIBIOTIC BB-K8; Amiglyde-V; Amikacin & Tumor Necrosis Factor; Amikacin (USP); Amikacina [INN-Spanish]; Amikacine [INN-French]; Amikacinum [INN-Latin]; Amikin(Disulfate); Antibiotic BB-K 8; BB-K 8; BB-K8; Amiglyde-V (TN); Amikacin (USP/INN); Amikacin [USAN:BAN:INN]; O-3-Amino-3-deoxy-alpha-D-glucopyranosyl-(1-4)-O-(6-amino-6-deoxy-alpha-D-glucopyranosyl-(1-6))-N(sup 3)-(4-amino-L-2-hydroxybutyryl)-2-deoxy-L-streptamine; O-3-amino-3-deoxy-alpha-D-glucopyranosyl-(1->4)-O-(6-amino-6-deoxy-alpha-D-glucopyranosyl-(1->6))-N(3)-(4-amino-L-2-hydroxybutyryl)-2-deoxy-L-streptamine; O-3-Amino-3-deoxy-.alpha.-D-glucopyranosyl-(1->6)-O-[6-amino-6-deoxy-.alpha.-D-glucopyranosyl-(1->4)]-1-(4-amino-2-hydroxy-1-oxobutyl)-2-deoxy-D-streptamine; (2S)-4-amino-N-[(1R,2S,3S,4R,5S)-5-amino-2-(3-amino-3-deoxy-alpha-D-glucopyranosyloxy)-4-(6-amino-6-deoxy-alpha-D-glucopyranosyloxy)-3-hydroxycyclohexyl]-2-hydroxybutanamide; (2S)-4-amino-N-[(1R,2S,3S,4R,5S)-5-amino-2-[(2S,3R,4S,5S,6R)-4-amino-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-4-[(2R,3R,4S,5S,6R)-6-(aminomethyl)-3,4,5-trihydroxyoxan-2-yl]oxy-3-hydroxycyclohexyl]-2-hydroxybutanamide; (2S)-4-amino-N-{(1R,2S,3S,4R,5S)-5-amino-2-[(3-amino-3-deoxy-alpha-D-glucopyranosyl)oxy]-4-[(6-amino-6-deoxy-alpha-D-glucopyranosyl)oxy]-3-hydroxycyclohexyl}-2-hydroxybutanamide; 1-N-(L(-)-gamma-Amino-alpha-hydroxybutyryl)kanamycin A
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Indication
In total 2 Indication(s)
Bacterial infection [ICD-11: 1A00-1C4Z]
Approved
[1]
HIV-infected patients with tuberculosis [ICD-11: 1B10-1B14]
Investigative
[1]
Structure
Drug Resistance Disease(s)
Disease(s) with Clinically Reported Resistance for This Drug (4 diseases)
Bacterial infection [ICD-11: 1A00-1C4Z]
[2]
Escherichia coli intestinal infection [ICD-11: 1A03]
[2]
Non-tuberculous mycobacteria infection [ICD-11: 1B21]
[3]
Pneumonia [ICD-11: CA40]
[4]
Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (2 diseases)
Bacterial infection [ICD-11: 1A00-1C4Z]
[5]
Escherichia coli intestinal infection [ICD-11: 1A03]
[6]
Target Staphylococcus 30S ribosomal subunit (Stap-coc pbp2) F4NA87_STAAU [1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
C22H43N5O13
IsoSMILES
C1[C@@H]([C@H]([C@@H]([C@H]([C@@H]1NC(=O)[C@H](CCN)O)O[C@@H]2[C@@H]([C@H]([C@@H]([C@H](O2)CO)O)N)O)O)O[C@@H]3[C@@H]([C@H]([C@@H]([C@H](O3)CN)O)O)O)N
InChI
1S/C22H43N5O13/c23-2-1-8(29)20(36)27-7-3-6(25)18(39-22-16(34)15(33)13(31)9(4-24)37-22)17(35)19(7)40-21-14(32)11(26)12(30)10(5-28)38-21/h6-19,21-22,28-35H,1-5,23-26H2,(H,27,36)/t6-,7+,8-,9+,10+,11-,12+,13+,14+,15-,16+,17-,18+,19-,21+,22+/m0/s1
InChIKey
LKCWBDHBTVXHDL-RMDFUYIESA-N
PubChem CID
37768
ChEBI ID
CHEBI:2637
TTD Drug ID
D0Y3MO
INTEDE ID
DR2167
DrugBank ID
DB00479
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
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Bacterial infection [ICD-11: 1A00-1C4Z]
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: 16S rRNA (guanine(1405)-N(7))-methyltransferase (RMTA) [7]
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.
       Drug Inactivation by Structure Modification (DISM) Click to Show/Hide
Key Molecule: Aminoglycoside N(6')-acetyltransferase type 1 (A6AC1) [8]
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
Pseudomonas aeruginosa Nk0001 287
Pseudomonas aeruginosa Nk0002 287
Pseudomonas aeruginosa Nk0003 287
Pseudomonas aeruginosa Nk0004 287
Pseudomonas aeruginosa Nk0005 287
Pseudomonas aeruginosa Nk0006 287
Pseudomonas aeruginosa Nk0007 287
Pseudomonas aeruginosa Nk0008 287
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 acetyltransferase (AAC) [9]
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 DH5alpha 668369
Experiment for
Molecule Alteration
PCR mapping and sequencing assay
Experiment for
Drug Resistance
Macrodilution broth method assay
Mechanism Description Aac(3)-Ic gene could contribute to aminoglycoside resistance with a pattern typical of AAC(3)-I enzymes.
Key Molecule: Acetylpolyamine amidohydrolase (APAH) [2]
Molecule Alteration Expression
Inherence
Resistant Disease Achromobacter xylosoxydans infection [ICD-11: 1A00-1C4Z]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Escherichia coli 668369
Achromobacter xylosoxydans subsp. denitrificans AX-22 85698
Escherichia coli MkD-135 562
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) [5]
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
Escherichia coli strain k802 562
Streptococcus faecnlis strain JHZ-15 1351
Experiment for
Molecule Alteration
Chemical sequencing method assay
Experiment for
Drug Resistance
Disc sensitivity tests assay
Mechanism Description Strain BM2182 was examined for aminoglyco- side-modifying activities. That kanamycin B was modified and tobramycin (3'-deoxykanamycin B) was not, indicates that the 3'-hydroxyl group is the site of phosphorylation. That butirosin, lividomycin A, and amikacin were phosphorylated indicates that the enzyme is APH-III.
Key Molecule: Aminoglycoside 3'-phosphotransferase (A3AP) [10]
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
Escherichia coli DH5alpha 668369
Escherichia coli Ecmrs144 562
Escherichia coli Ecmrs150 562
Escherichia coli Ecmrs151 562
Escherichia coli strain 83-125 562
Escherichia coli strain 83-75 562
Escherichia coli strain JM83 562
Escherichia coli strain JM83(pRPG101) 562
Escherichia coli strain M8820Mu 562
Escherichia coli strain MC1065 562
Escherichia coli strain MC1065(pRPG101) 562
Escherichia coli strain POII1681 562
Escherichia coli strain PRC930(pAO43::Tn9O3) 562
Klebsiella pneumoniae strains 573
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 N(3)-acetyltransferase III (A3AC3) [11], [12]
Molecule Alteration Expression
Inherence
Resistant Disease Bacterial infection [ICD-11: 1A00-1C4Z]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Escherichia coli strain DH5a 668369
Serratia marcescens strain 82041944 615
Experiment for
Drug Resistance
Broth microdilution method assay
Mechanism Description The AAC(3)-V resistance mechanism is characterized by high-level resistance to the aminoglycosides gentamicin, netilmicin, 2'-N-ethylnetilmicin, and 6'-N-ethylnetilmicin and moderate resistance levels to tobramycin.
       Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: TolC family outer membrane protein (TOLC) [1]
Molecule Alteration Expression
Up-regulation
Resistant Disease Bacterial infection [ICD-11: 1A00-1C4Z]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Acinetobacter baumannii AYE WT 509173
Acinetobacter baumannii AYE detaabuO 509173
Acinetobacter baumannii AYE detaabuO Omega abuO 509173
Experiment for
Molecule Alteration
Whole genome sequence assay
Experiment for
Drug Resistance
Disk diffusion test assay; E-strip test assay
Mechanism Description AbuO, an OMP, confers broad-spectrum antimicrobial resistance via active efflux in A. baumannii.
Escherichia coli intestinal infection [ICD-11: 1A03]
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Drug Inactivation by Structure Modification (DISM) Click to Show/Hide
Key Molecule: Aminoglycoside acetyltransferase (AAC) [13]
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
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: Acetylpolyamine amidohydrolase (APAH) [2]
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
Achromobacter xylosoxydans subsp. denitrificans AX-22 85698
Escherichia coli MkD-135 562
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 2'-N-acetyltransferase (A2NA) [6]
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 DH5a 668369
Escherichia coli strain XLI-Blue 562
Providencia stuartii strain PR50 588
Providencia stuartii strain SCH75082831A 588
Experiment for
Molecule Alteration
DNA sequencing assay
Experiment for
Drug Resistance
Microdilution plates assay
Mechanism Description E.coli DH5alpha/pR 1000 demonstrated an AAC(2')-Ia resistance profile,with gentamicin, tobramycin, netilmicin, and 6'-Nethylnetilmicin MICs increased over those seen with E.coli DH5alpha. In addition, E.coli DH5alpha/pR 1000 did not show an elevated 2'-N-ethylnetilmicin MIC (MIC was 0.25ug/ml). Therefore, pR1000 encoded an enzyme capable of acetylating 6'-N-ethylnetilmicin but not 2'-N-ethylnetilmicin, suggesting 2'-N-acetyltransferase activity. DH5alpha/pSCH4500, which contains a subcloned 1.3-kb fragment, also demonstrated an AAC(2')-Ia resistance profile.
Key Molecule: Aminoglycoside 3'-phosphotransferase (A3AP) [10]
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
Escherichia coli DH5alpha 668369
Escherichia coli Ecmrs144 562
Escherichia coli Ecmrs150 562
Escherichia coli Ecmrs151 562
Escherichia coli strain 83-125 562
Escherichia coli strain 83-75 562
Escherichia coli strain JM83 562
Escherichia coli strain JM83(pRPG101) 562
Escherichia coli strain M8820Mu 562
Escherichia coli strain MC1065 562
Escherichia coli strain MC1065(pRPG101) 562
Escherichia coli strain POII1681 562
Escherichia coli strain PRC930(pAO43::Tn9O3) 562
Klebsiella pneumoniae strains 573
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) [14]
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
Acinetobacter baumannii strain BM2580 470
Bacillus subtilis strain BS168 1423
Experiment for
Molecule Alteration
SDS-PAGE assay
Mechanism Description The shuttle piasmid pAT239 was constructed by inserting the H/ndlll-linearized staphyococcal piasmid pC194 into the unique H/ndlll site of pAT235. This piasmid, which confers resistance to ampicillin, chloramphenicol and kanamycin in Escherichia coli, was introduced by transformation into Bacillus subtilis strain BS168.
Non-tuberculous mycobacteria infection [ICD-11: 1B21]
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Drug Inactivation by Structure Modification (DISM) Click to Show/Hide
Key Molecule: OXA-23 carbapenemase (BLA OXA-23) [3]
Molecule Alteration Expression
Up-regulation
Resistant Disease Cutaneous bacterial infection [ICD-11: 1B21.4]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Acinetobacter baumannii isolates 470
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
Broth microdilution method assay; Agar dilution method assay
Mechanism Description The isolate was resistant to antibiotics other than ampicillin-sulbactam and colistin, suggesting drug resistance due to carbapenemase production by OXA-23.carbapenem resistance in the isolated carbapenem-resistant A. baumannii strain was at least partially conferred by bla OXA-23-like carbapenemase.
ICD-12: Respiratory system diseases
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Pneumonia [ICD-11: CA40]
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Drug Inactivation by Structure Modification (DISM) Click to Show/Hide
Key Molecule: Aminoglycoside 3'-phosphotransferase (A3AP) [10]
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
Escherichia coli DH5alpha 668369
Escherichia coli Ecmrs144 562
Escherichia coli Ecmrs150 562
Escherichia coli Ecmrs151 562
Escherichia coli strain 83-125 562
Escherichia coli strain 83-75 562
Escherichia coli strain JM83 562
Escherichia coli strain JM83(pRPG101) 562
Escherichia coli strain M8820Mu 562
Escherichia coli strain MC1065 562
Escherichia coli strain MC1065(pRPG101) 562
Escherichia coli strain POII1681 562
Escherichia coli strain PRC930(pAO43::Tn9O3) 562
Klebsiella pneumoniae strains 573
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) [14]
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
Acinetobacter baumannii strain BM2580 470
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) Click to Show/Hide
Key Molecule: Multidrug efflux SMR transporter (ABES) [4]
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
Molecule Alteration
Fluorometric efflux assay
Experiment for
Drug Resistance
Broth dilution assay
Mechanism Description The abeS gene product conferred resistance to various antimicrobial compounds through an efflux mechanism.
ICD-16: Genitourinary system diseases
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Urinary tract infection [ICD-11: GC08]
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Drug Inactivation by Structure Modification (DISM) Click to Show/Hide
Key Molecule: Aminoglycoside (3'') (9) adenylyltransferase (AADA) [15]
Molecule Alteration Expression
Inherence
Sensitive Disease Urinary tract infection [ICD-11: GC08.1]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Escherichia coli serogroup O11 1095705
Escherichia coli serogroup O17 1010800
Escherichia coli serogroup O73 2170725
Escherichia coli serogroup O77 562
Experiment for
Molecule Alteration
PCR amplification and sequence alignments assay
Experiment for
Drug Resistance
Microdilution method assay
Mechanism Description All the UTI outbreak CgA strains in this study contained the same class 1 integron dfrA17-aadA5 gene cassette arrangement with 100% sequence match, suggesting clonal spread of the bacterial strain itself. While aminoglycoside adenyltransferase A (aadA ) and dihydrofolate reductase A (dfrA ), encoding resistance to streptomycin and trimethoprim.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Dihydrofolate reductase (DHFR) [15]
Molecule Alteration Expression
Inherence
Sensitive Disease Urinary tract infection [ICD-11: GC08.1]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Escherichia coli serogroup O11 1095705
Escherichia coli serogroup O17 1010800
Escherichia coli serogroup O73 2170725
Escherichia coli serogroup O77 562
Experiment for
Molecule Alteration
PCR amplification and sequence alignments assay
Experiment for
Drug Resistance
Microdilution method assay
Mechanism Description All the UTI outbreak CgA strains in this study contained the same class 1 integron dfrA17-aadA5 gene cassette arrangement with 100% sequence match, suggesting clonal spread of the bacterial strain itself. While aminoglycoside adenyltransferase A (aadA ) and dihydrofolate reductase A (dfrA ), encoding resistance to streptomycin and trimethoprim.
Key Molecule: Dihydrofolate reductase (DHFR) [15]
Molecule Alteration Expression
Inherence
Sensitive Disease Urinary tract infection [ICD-11: GC08.1]
Experimental Note Identified from the Human Clinical Data
In Vitro Model Escherichia coli serogroup O11 1095705
Escherichia coli serogroup O17 1010800
Escherichia coli serogroup O73 2170725
Escherichia coli serogroup O77 562
Experiment for
Molecule Alteration
PCR amplification and sequence alignments assay
Experiment for
Drug Resistance
Microdilution method assay
Mechanism Description All the UTI outbreak CgA strains in this study contained the same class 1 integron dfrA17-aadA5 gene cassette arrangement with 100% sequence match, suggesting clonal spread of the bacterial strain itself. While aminoglycoside adenyltransferase A (aadA ) and dihydrofolate reductase A (dfrA ), encoding resistance to streptomycin and trimethoprim.
References
Ref 1 AbuO, a TolC-like outer membrane protein of Acinetobacter baumannii, is involved in antimicrobial and oxidative stress resistance. Antimicrob Agents Chemother. 2015 Feb;59(2):1236-45. doi: 10.1128/AAC.03626-14. Epub 2014 Dec 15.
Ref 2 In70 of plasmid pAX22, a bla(VIM-1)-containing integron carrying a new aminoglycoside phosphotransferase gene cassette. Antimicrob Agents Chemother. 2001 Apr;45(4):1249-53. doi: 10.1128/AAC.45.4.1249-1253.2001.
Ref 3 Daptomycin .J Antimicrob Chemother. 2018 Jan 1;73(1):1-11. doi: 10.1093/jac/dkx349. 10.1093/jac/dkx349
Ref 4 Role of AbeS, a novel efflux pump of the SMR family of transporters, in resistance to antimicrobial agents in Acinetobacter baumannii. Antimicrob Agents Chemother. 2009 Dec;53(12):5312-6. doi: 10.1128/AAC.00748-09. Epub 2009 Sep 21.
Ref 5 Nucleotide sequence of the Streptococcus faecalis plasmid gene encoding the 3'5"-aminoglycoside phosphotransferase type III. Gene. 1983 Sep;23(3):331-41. doi: 10.1016/0378-1119(83)90022-7.
Ref 6 Characterization and transcriptional regulation of the 2'-N-acetyltransferase gene from Providencia stuartii. J Bacteriol. 1993 Oct;175(20):6492-8. doi: 10.1128/jb.175.20.6492-6498.1993.
Ref 7 Acquisition of 16S rRNA methylase gene in Pseudomonas aeruginosa. Lancet. 2003 Dec 6;362(9399):1888-93. doi: 10.1016/S0140-6736(03)14959-8.
Ref 8 Identification and characterization of a novel aac(6')-Iag associated with the blaIMP-1-integron in a multidrug-resistant Pseudomonas aeruginosa. PLoS One. 2013 Aug 12;8(8):e70557. doi: 10.1371/journal.pone.0070557. eCollection 2013.
Ref 9 Novel 3-N-aminoglycoside acetyltransferase gene, aac(3)-Ic, from a Pseudomonas aeruginosa integron. Antimicrob Agents Chemother. 2003 May;47(5):1746-8. doi: 10.1128/AAC.47.5.1746-1748.2003.
Ref 10 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 11 Cloning and DNA sequence analysis of an aac(3)-Vb gene from Serratia marcescens. Antimicrob Agents Chemother. 1992 Oct;36(10):2222-7. doi: 10.1128/AAC.36.10.2222.
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