Disease Information

General Information of the Disease (ID: DIS00134)
Name
Urinary tract infection
ICD
ICD-11: GC08
Resistance Map
Type(s) of Resistant Mechanism of This Disease
  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 Drug
Approved Drug(s)
12 drug(s) in total
Click to Show/Hide the Full List of Drugs
Amikacin
Click to Show/Hide
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) [1]
Sensitive Disease Urinary tract infection [ICD-11: GC08.1]
Sensitive Drug Amikacin
 Drug Info 
Molecule Alteration Expression
Inherence
 Molecule Info 
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) [1]
Sensitive Disease Urinary tract infection [ICD-11: GC08.1]
Sensitive Drug Amikacin
 Drug Info 
Molecule Alteration Expression
Inherence
 Molecule Info 
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) [1]
Sensitive Disease Urinary tract infection [ICD-11: GC08.1]
Sensitive Drug Amikacin
 Drug Info 
Molecule Alteration Expression
Inherence
 Molecule Info 
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.
Ampicillin
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Drug Inactivation by Structure Modification (DISM) Click to Show/Hide
Key Molecule: Aminoglycoside (3'') (9) adenylyltransferase (AADA) [1]
Resistant Disease Urinary tract infection [ICD-11: GC08.1]
Resistant Drug Ampicillin
 Drug Info 
Molecule Alteration Expression
Inherence
 Molecule Info 
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: Aminoglycoside (3'') (9) adenylyltransferase (AADA) [1]
Resistant Disease Urinary tract infection [ICD-11: GC08.1]
Resistant Drug Ampicillin
 Drug Info 
Molecule Alteration Expression
Inherence
 Molecule Info 
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) [1]
Resistant Disease Urinary tract infection [ICD-11: GC08.1]
Resistant Drug Ampicillin
 Drug Info 
Molecule Alteration Expression
Inherence
 Molecule Info 
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) [1]
Resistant Disease Urinary tract infection [ICD-11: GC08.1]
Resistant Drug Ampicillin
 Drug Info 
Molecule Alteration Expression
Inherence
 Molecule Info 
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.
Ciprofloxacin XR
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Drug Inactivation by Structure Modification (DISM) Click to Show/Hide
Key Molecule: Aminoglycoside (3'') (9) adenylyltransferase (AADA) [1]
Resistant Disease Urinary tract infection [ICD-11: GC08.1]
Resistant Drug Ciprofloxacin XR
 Drug Info 
Molecule Alteration Expression
Inherence
 Molecule Info 
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: Aminoglycoside (3'') (9) adenylyltransferase (AADA) [1]
Resistant Disease Urinary tract infection [ICD-11: GC08.1]
Resistant Drug Ciprofloxacin XR
 Drug Info 
Molecule Alteration Expression
Inherence
 Molecule Info 
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) [1]
Resistant Disease Urinary tract infection [ICD-11: GC08.1]
Resistant Drug Ciprofloxacin XR
 Drug Info 
Molecule Alteration Expression
Inherence
 Molecule Info 
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) [1]
Resistant Disease Urinary tract infection [ICD-11: GC08.1]
Resistant Drug Ciprofloxacin XR
 Drug Info 
Molecule Alteration Expression
Inherence
 Molecule Info 
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.
Clindamycin
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: ABC protein lsaC (lsaC-Unclear) [2]
Resistant Disease Klebsiella pneumoniae [ICD-11: CA40.0]
Resistant Drug Clindamycin
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Escherichia coli TOP10 83333
Staphylococcus aureus ATCC 29213 1280
Streptococcus agalactiae UCN70 1311
Streptococcus agalactiae isolates 1311
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.
Co-trimoxazole
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Dihydrofolate reductase (DHFR) [1]
Resistant Disease Urinary tract infection [ICD-11: GC08.1]
Resistant Drug Co-trimoxazole
 Drug Info 
Molecule Alteration Expression
Inherence
 Molecule Info 
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) [1]
Resistant Disease Urinary tract infection [ICD-11: GC08.1]
Resistant Drug Co-trimoxazole
 Drug Info 
Molecule Alteration Expression
Inherence
 Molecule Info 
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.
  Drug Inactivation by Structure Modification (DISM) Click to Show/Hide
Key Molecule: Aminoglycoside (3'') (9) adenylyltransferase (AADA) [1]
Resistant Disease Urinary tract infection [ICD-11: GC08.1]
Resistant Drug Co-trimoxazole
 Drug Info 
Molecule Alteration Expression
Inherence
 Molecule Info 
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: Aminoglycoside (3'') (9) adenylyltransferase (AADA) [1]
Resistant Disease Urinary tract infection [ICD-11: GC08.1]
Resistant Drug Co-trimoxazole
 Drug Info 
Molecule Alteration Expression
Inherence
 Molecule Info 
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.
Colistin
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Transcriptional regulatory protein (PHOP) [3]
Resistant Disease Klebsiella pneumoniae [ICD-11: CA40.0]
Resistant Drug Colistin
 Drug Info 
Molecule Alteration Missense mutation
p.D191Y
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Klebsiella pneumoniae kp75 573
Klebsiella pneumoniae ATCC 53153 573
Experiment for
Molecule Alteration		 Whole genome sequence assay
Experiment for
Drug Resistance		 Broth microdilution method assay
Mechanism Description The mutated protein PhoP activates the transcription of the pmrHFIJkLM operon, the product of which leads to synthesis of L-amino-arabinose and ultimately to colistin resistance in k. pneumoniae.These modifications create a more positively charged lipopolysaccharide and thus reduce the affinity of LPS to positively charged polymyxins.
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Multifunctional fusion protein (LPXA) [4], [5]
Resistant Disease Acinetobacter baumannii infection [ICD-11: CA40.4]
Resistant Drug Colistin
 Drug Info 
Molecule Alteration Frameshift mutation
c.90del
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Acinetobacter baumannii ATCC 19606 575584
Acinetobacter baumannii FADDI008 470
Experiment for
Molecule Alteration		 Whole genome sequence assay
Experiment for
Drug Resistance		 Broth microdilution method assay
Mechanism Description A critical first step in the action of polymyxins is the electrostatic interaction between the positively charged peptide and the negatively charged lipid A, the endotoxic component of lipopolysaccharide (LPS).A. baumannii type strain ATCC 19606, colistin-resistant variants contain mutations within genes essential for lipid A biosynthesis (either lpxA, lpxC, or lpxD) and that these strains have lost the ability to produce lipid A and therefore LPS.
Key Molecule: Multifunctional fusion protein (LPXA) [4], [5]
Resistant Disease Acinetobacter baumannii infection [ICD-11: CA40.4]
Resistant Drug Colistin
 Drug Info 
Molecule Alteration Missense mutation
p.H159D
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Acinetobacter baumannii AL1844 470
Experiment for
Molecule Alteration		 Whole genome sequence assay
Experiment for
Drug Resistance		 Broth microdilution method assay
Mechanism Description A critical first step in the action of polymyxins is the electrostatic interaction between the positively charged peptide and the negatively charged lipid A, the endotoxic component of lipopolysaccharide (LPS).A. baumannii type strain ATCC 19606, colistin-resistant variants contain mutations within genes essential for lipid A biosynthesis (either lpxA, lpxC, or lpxD) and that these strains have lost the ability to produce lipid A and therefore LPS.
Key Molecule: Multifunctional fusion protein (LPXA) [4], [5]
Resistant Disease Acinetobacter baumannii infection [ICD-11: CA40.4]
Resistant Drug Colistin
 Drug Info 
Molecule Alteration Missense mutation
c.700C>T
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Acinetobacter baumannii AL1845 470
Experiment for
Molecule Alteration		 Whole genome sequence assay
Experiment for
Drug Resistance		 Broth microdilution method assay
Mechanism Description A critical first step in the action of polymyxins is the electrostatic interaction between the positively charged peptide and the negatively charged lipid A, the endotoxic component of lipopolysaccharide (LPS).A. baumannii type strain ATCC 19606, colistin-resistant variants contain mutations within genes essential for lipid A biosynthesis (either lpxA, lpxC, or lpxD) and that these strains have lost the ability to produce lipid A and therefore LPS.
Key Molecule: Multifunctional fusion protein (LPXA) [4], [5]
Resistant Disease Acinetobacter baumannii infection [ICD-11: CA40.4]
Resistant Drug Colistin
 Drug Info 
Molecule Alteration Missense mutation
p.G68D
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Acinetobacter baumannii AL1846 470
Experiment for
Molecule Alteration		 Whole genome sequence assay
Experiment for
Drug Resistance		 Broth microdilution method assay
Mechanism Description A critical first step in the action of polymyxins is the electrostatic interaction between the positively charged peptide and the negatively charged lipid A, the endotoxic component of lipopolysaccharide (LPS).A. baumannii type strain ATCC 19606, colistin-resistant variants contain mutations within genes essential for lipid A biosynthesis (either lpxA, lpxC, or lpxD) and that these strains have lost the ability to produce lipid A and therefore LPS.
Key Molecule: Multifunctional fusion protein (LPXA) [4], [5]
Resistant Disease Acinetobacter baumannii infection [ICD-11: CA40.4]
Resistant Drug Colistin
 Drug Info 
Molecule Alteration Frameshift mutation
c.391_421del
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Acinetobacter baumannii ATCC 19606 575584
Acinetobacter baumannii FADDI008 470
Experiment for
Molecule Alteration		 Whole genome sequence assay
Experiment for
Drug Resistance		 Broth microdilution method assay
Mechanism Description A critical first step in the action of polymyxins is the electrostatic interaction between the positively charged peptide and the negatively charged lipid A, the endotoxic component of lipopolysaccharide (LPS).A. baumannii type strain ATCC 19606, colistin-resistant variants contain mutations within genes essential for lipid A biosynthesis (either lpxA, lpxC, or lpxD) and that these strains have lost the ability to produce lipid A and therefore LPS.
Key Molecule: Multifunctional fusion protein (LPXA) [4], [5]
Resistant Disease Acinetobacter baumannii infection [ICD-11: CA40.4]
Resistant Drug Colistin
 Drug Info 
Molecule Alteration Missense mutation
p.Q72K
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Acinetobacter baumannii AL1848 470
Experiment for
Molecule Alteration		 Whole genome sequence assay
Experiment for
Drug Resistance		 Broth microdilution method assay
Mechanism Description A critical first step in the action of polymyxins is the electrostatic interaction between the positively charged peptide and the negatively charged lipid A, the endotoxic component of lipopolysaccharide (LPS).A. baumannii type strain ATCC 19606, colistin-resistant variants contain mutations within genes essential for lipid A biosynthesis (either lpxA, lpxC, or lpxD) and that these strains have lost the ability to produce lipid A and therefore LPS.
Key Molecule: Multifunctional fusion protein (LPXA) [4], [5]
Resistant Disease Acinetobacter baumannii infection [ICD-11: CA40.4]
Resistant Drug Colistin
 Drug Info 
Molecule Alteration Frameshift mutation
c.76_78del
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Acinetobacter baumannii ATCC 19606 575584
Acinetobacter baumannii FADDI008 470
Experiment for
Molecule Alteration		 Whole genome sequence assay
Experiment for
Drug Resistance		 Broth microdilution method assay
Mechanism Description A critical first step in the action of polymyxins is the electrostatic interaction between the positively charged peptide and the negatively charged lipid A, the endotoxic component of lipopolysaccharide (LPS).A. baumannii type strain ATCC 19606, colistin-resistant variants contain mutations within genes essential for lipid A biosynthesis (either lpxA, lpxC, or lpxD) and that these strains have lost the ability to produce lipid A and therefore LPS.
Key Molecule: Multifunctional fusion protein (LPXA) [4], [5]
Resistant Disease Acinetobacter baumannii infection [ICD-11: CA40.4]
Resistant Drug Colistin
 Drug Info 
Molecule Alteration Frameshift mutation
c.364_809del
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Acinetobacter baumannii ATCC 19606 575584
Acinetobacter baumannii FADDI008 470
Experiment for
Molecule Alteration		 Whole genome sequence assay
Experiment for
Drug Resistance		 Broth microdilution method assay
Mechanism Description A critical first step in the action of polymyxins is the electrostatic interaction between the positively charged peptide and the negatively charged lipid A, the endotoxic component of lipopolysaccharide (LPS).A. baumannii type strain ATCC 19606, colistin-resistant variants contain mutations within genes essential for lipid A biosynthesis (either lpxA, lpxC, or lpxD) and that these strains have lost the ability to produce lipid A and therefore LPS.
Dalfopristin
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: ABC protein lsaC (lsaC-Unclear) [2]
Resistant Disease Klebsiella pneumoniae [ICD-11: CA40.0]
Resistant Drug Dalfopristin
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Escherichia coli TOP10 83333
Staphylococcus aureus ATCC 29213 1280
Streptococcus agalactiae UCN70 1311
Streptococcus agalactiae isolates 1311
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.
Fluconazole
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Lanosterol 14-alpha demethylase (ERG11) [6]
Resistant Disease Urinary tract infection [ICD-11: GC08.1]
Resistant Drug Fluconazole
 Drug Info 
Molecule Alteration Missense mutation
G42S
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Urinary Candida spp. Isolated 5475
Experiment for
Molecule Alteration		 RT-PCR; PCR; GeneSeq assay
Experiment for
Drug Resistance		 Germ tube formation assay; Tween 80 opacity assay; MTP assay; Fluconazole susceptibility testing; Resistance modulation assay; Rhodamine efflux assay
Mechanism Description Fluconazole susceptibility testing of 34 urinary Candida isolates indicated that 76.5% were FLC-R, with a higher prevalence of resistance recorded in non-albicans Candida spp. (88.9%) than in Candida albicans (62.5%). The calculated Spearman's correlation coefficients implied significant positive correlations between fluconazole minimum inhibitory concentrations and both biofilm formation and phospholipase production. Real-time PCR results revealed that most FLC-R isolates (60%) significantly overexpressed at least one efflux pump gene, while 42.3% significantly upregulated the ERG11 gene. The most prevalent mutation detected upon ERG11 sequencing was G464S, which is conclusively linked to fluconazole resistance.
Gentamicin
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Drug Inactivation by Structure Modification (DISM) Click to Show/Hide
Key Molecule: Aminoglycoside (3'') (9) adenylyltransferase (AADA) [1]
Resistant Disease Urinary tract infection [ICD-11: GC08.1]
Resistant Drug Gentamicin
 Drug Info 
Molecule Alteration Expression
Inherence
 Molecule Info 
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: Aminoglycoside (3'') (9) adenylyltransferase (AADA) [1]
Resistant Disease Urinary tract infection [ICD-11: GC08.1]
Resistant Drug Gentamicin
 Drug Info 
Molecule Alteration Expression
Inherence
 Molecule Info 
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) [1]
Resistant Disease Urinary tract infection [ICD-11: GC08.1]
Resistant Drug Gentamicin
 Drug Info 
Molecule Alteration Expression
Inherence
 Molecule Info 
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) [1]
Resistant Disease Urinary tract infection [ICD-11: GC08.1]
Resistant Drug Gentamicin
 Drug Info 
Molecule Alteration Expression
Inherence
 Molecule Info 
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.
Lincomycin
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: ABC protein lsaC (lsaC-Unclear) [2]
Resistant Disease Klebsiella pneumoniae [ICD-11: CA40.0]
Resistant Drug Lincomycin
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Escherichia coli TOP10 83333
Staphylococcus aureus ATCC 29213 1280
Streptococcus agalactiae UCN70 1311
Streptococcus agalactiae isolates 1311
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.
Tiamulin
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: ABC protein lsaC (lsaC-Unclear) [2]
Resistant Disease Klebsiella pneumoniae [ICD-11: CA40.0]
Resistant Drug Tiamulin
 Drug Info 
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Escherichia coli TOP10 83333
Staphylococcus aureus ATCC 29213 1280
Streptococcus agalactiae UCN70 1311
Streptococcus agalactiae isolates 1311
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.
Trimethoprim
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Dihydrofolate reductase (DHFR) [7]
Resistant Disease Urinary tract infection [ICD-11: GC08.1]
Resistant Drug Trimethoprim
 Drug Info 
Molecule Alteration Expression
Inherence
 Molecule Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Escherichia coli 1387 562
Experiment for
Molecule Alteration		 PCR amplification and sequence alignments assay
Mechanism Description The most common resistant mechanism involves expressing trimethoprim insensitive variants of DHFR within mobile genetic elements, such as plasmids, transposons and integrons.
References
Ref 1 Global spread of mobile antimicrobial drug resistance determinants in human and animal Escherichia coli and Salmonella strains causing community-acquired infections. Clin Infect Dis. 2009 Aug 1;49(3):365-71. doi: 10.1086/600301.
Ref 2 Cross-resistance to lincosamides, streptogramins A, and pleuromutilins due to the lsa(C) gene in Streptococcus agalactiae UCN70. Antimicrob Agents Chemother. 2011 Apr;55(4):1470-4. doi: 10.1128/AAC.01068-10. Epub 2011 Jan 18.
Ref 3 Heteroresistance to colistin in Klebsiella pneumoniae associated with alterations in the PhoPQ regulatory system. Antimicrob Agents Chemother. 2015 May;59(5):2780-4. doi: 10.1128/AAC.05055-14. Epub 2015 Mar 2.
Ref 4 Colistin resistance in Acinetobacter baumannii is mediated by complete loss of lipopolysaccharide production. Antimicrob Agents Chemother. 2010 Dec;54(12):4971-7. doi: 10.1128/AAC.00834-10. Epub 2010 Sep 20.
Ref 5 Biological cost of different mechanisms of colistin resistance and their impact on virulence in Acinetobacter baumannii. Antimicrob Agents Chemother. 2014;58(1):518-26. doi: 10.1128/AAC.01597-13. Epub 2013 Nov 4.
Ref 6 Elucidation of the mechanisms of fluconazole resistance and repurposing treatment options against urinary Candida spp. isolated from hospitalized patients in Alexandria, Egypt. BMC Microbiol. 2024 Oct 1;24(1):383.
Ref 7 dfrA27, a new integron-associated trimethoprim resistance gene from Escherichia coli. J Antimicrob Chemother. 2009 Feb;63(2):405-6. doi: 10.1093/jac/dkn474. Epub 2008 Nov 13.

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