Drug Information

Drug (ID: DG00308) and It's Reported Resistant Information

• Name: Ampicillin
• Synonyms: ABPC; Acillin; Adobacillin; Alpen; Amblosin; Amcill; Amfipen; Aminobenzylpenicillin; Ampen; Ampichel; Ampicil; Ampicilina; Ampicillanyl; Ampicillina; Ampicilline; Ampicillinum; Ampicin; Ampifarm; Ampikel; Ampimed; Ampipenin; Ampiscel; Ampisyn; Ampivax; Ampivet; Amplacilina; Amplin; Amplipenyl; Amplisom; Amplital; Austrapen; Binotal; Bonapicillin; Britacil; Campicillin; Cimex; Copharcilin; Delcillin; Deripen; Divercillin; Doktacillin; Duphacillin; Grampenil; Guicitrina; Guicitrine; Lifeampil; Morepen; Norobrittin; Nuvapen; Omnipen; Orbicilina; Penbristol; Penbritin; Penbrock; Penicline; Penimic; Pensyn; Pentrex; Pentrexl; Pentrexyl; Polycillin; Ponecil; Princillin; Principen; QIDamp; Racenacillin; Rosampline;Roscillin; Semicillin; Servicillin; Sumipanto; Supen; Synpenin; Texcillin; Tokiocillin; Tolomol; Totacillin; Totalciclina; Totapen; Trifacilina; Ukapen; Ultrabion; Ultrabron; Vampen; Viccillin; Wypicil; Amfipen V; Amipenix S; Ampicillin A; Ampicillin Anhydrous; Ampicillin Base; Ampicillin acid; Ampicillin anhydrate; Ampicillina [DCIT]; Anhydrous ampicillin; Olin Kid; Pen A; Pen A Oral; Pen Ampil;Penbritin paediatric; Penbritin syrup; Pfizerpen A; Semicillin R; Viccillin S; AY 6108; BA 7305; BRL 1341; Bayer 5427; HI 63; P 50; Principen 125; Principen 250; Principen 500; SQ 17382; AB-PC; AB-PCSol; AY-6108; Ambidrin (TN); Ampi-Co; Ampi-Tab; Ampi-bol; Ampicilina [INN-Spanish]; Ampicilline [INN-French]; Ampicillinum [INN-Latin]; Ampipenin, nt3; Ampy-Penyl; Anhydrous ampicillin (JP15); BRL-1341; D-Ampicillin; D-Cillin; KS-R1; Novo-ampicillin; OMNIPEN (AMPICILLIN); Omnipen (TN); Omnipen-N; P-50; Penbritin-S; Penicillin, Aminobenzyl; Pfizerpen-A; Polycillin-N; Polyflex (Veterinary); Ro-Ampen; SK-Ampicillin; Totacillin (sodium); Totacillin-N; WY-5103; Ampicillin (USP/INN); AMPICILLIN (SEE ALSO AMPICILLIN TRIHYDRATE 7177-48-2); Ampicillin [USAN:BAN:INN:JAN]; Ampicillin [USAN:INN:BAN:JAN];D-(-)-Ampicillin; D-(-)-alpha-Aminobenzylpenicillin; D-(-)-alpha-Aminopenicillin; D-(-)-6-(alpha-Aminophenylacetamido)penicillanic acid; 6-(D(-)-alpha-Aminophenylacetamido)penicillanic acid; 6beta-[(2R)-2-amino-2-phenylacetamido]-2,2-dimethylpenam-3alpha-carbonyl; 6beta-[(2R)-2-amino-2-phenylacetamido]-2,2-dimethylpenam-3alpha-carboxylic acid
• 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 (11 diseases)
  Bacterial infection [ICD-11: 1A00-1C4Z]; [3]
  Cholera [ICD-11: 1A00]; [4]
  Escherichia coli intestinal infection [ICD-11: 1A03]; [3]
  Non-tuberculous mycobacteria infection [ICD-11: 1B21]; [5]
  Peritonitis [ICD-11: DC50]; [6]
  Pharyngitis [ICD-11: CA02]; [7]
  Pneumonia [ICD-11: CA40]; [8]
  Shigellosis [ICD-11: 1A02]; [9]
  Tissue pyogenic bacterial infection [ICD-11: 1B7Y]; [10]
  Ulcer [ICD-11: EH90]; [5]
  Urinary tract infection [ICD-11: GC08]; [11]
  Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (2 diseases)
  Escherichia coli intestinal infection [ICD-11: 1A03]; [12]
  Periodontal disease [ICD-11: DA0C]; [13]
• Target: Bacterial Penicillin binding protein (Bact PBP); NOUNIPROTAC; [1]
• Formula: C16H19N3O4S
• IsoSMILES: CC1([C@@H](N2[C@H](S1)[C@@H](C2=O)NC(=O)[C@@H](C3=CC=CC=C3)N)C(=O)O)C
• InChI: 1S/C16H19N3O4S/c1-16(2)11(15(22)23)19-13(21)10(14(19)24-16)18-12(20)9(17)8-6-4-3-5-7-8/h3-7,9-11,14H,17H2,1-2H3,(H,18,20)(H,22,23)/t9-,10-,11+,14-/m1/s1
• InChIKey: AVKUERGKIZMTKX-NJBDSQKTSA-N
• PubChem CID: 6249
• ChEBI ID: CHEBI:28971
• TTD Drug ID: D0YA9Z
• VARIDT ID: DR00712
• INTEDE ID: DR2177
• DrugBank ID: DB00415

Type(s) of Resistant Mechanism of This Drug

  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

Cholera [ICD-11: 1A00]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Erythromycin esterase (EREA2) [4]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Vibrio cholerae infection [ICD-11: 1A00.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Vibrio cholerae PG153/1; 666
• In Vitro Model: Vibrio cholerae PG170; 666
• In Vitro Model: Vibrio cholerae PL96; 666
• Experiment for Molecule Alteration: PCR and DNA sequencing assay
• Experiment for Drug Resistance: Commercial antimicrobial discs assay
• Mechanism Description: The expression of dfrA5, ereA2 lead to drug resistance.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Aminoglycoside (3'') (9) adenylyltransferase (AADA) [4]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Vibrio cholerae infection [ICD-11: 1A00.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Vibrio cholerae O26 strain AS482; 567107
• In Vitro Model: Vibrio cholerae O39 strain AS634; 666
• Experiment for Molecule Alteration: PCR and DNA sequencing assay
• Experiment for Drug Resistance: Commercial antimicrobial discs assay
• Mechanism Description: The expression of aadA1-S lead to drug resistance.

Key Molecule: Dihydrofolate reductase (DHFR) [4]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Vibrio cholerae infection [ICD-11: 1A00.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Vibrio cholerae O62 strain AS438; 666
• In Vitro Model: Vibrio cholerae PG149a; 666
• In Vitro Model: Vibrio cholerae PG224; 666
• In Vitro Model: Vibrio cholerae PG262(b); 666
• In Vitro Model: Vibrio cholerae PG9; 666
• In Vitro Model: Vibrio cholerae PG95; 666
• In Vitro Model: Vibrio cholerae PL1; 666
• In Vitro Model: Vibrio cholerae PL61; 666
• In Vitro Model: Vibrio cholerae PL78/6; 666
• In Vitro Model: Vibrio cholerae PL91; 666
• In Vitro Model: Vibrio cholerae PG92; 666
• Experiment for Molecule Alteration: PCR and DNA sequencing assay
• Experiment for Drug Resistance: Commercial antimicrobial discs assay
• Mechanism Description: The expression of dfrA1 lead to drug resistance.

Key Molecule: Dihydrofolate reductase (DHFR) [4]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Vibrio cholerae infection [ICD-11: 1A00.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Vibrio cholerae PG153/1; 666
• In Vitro Model: Vibrio cholerae PG170; 666
• In Vitro Model: Vibrio cholerae PL96; 666
• Experiment for Molecule Alteration: PCR and DNA sequencing assay
• Experiment for Drug Resistance: Commercial antimicrobial discs assay
• Mechanism Description: The expression of dfrA15 lead to drug resistance.

Bacterial infection [ICD-11: 1A00-1C4Z]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Beta-lactamase (BLA) [1], [2]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Mycobacterium tuberculosis H37Rv; 83332
• In Vitro Model: Escherichia coli DH10B; 316385
• In Vitro Model: Mycobacterium smegmatis PM274; 1772
• In Vitro Model: Mycobacterium smegmatis PM759; 1772
• In Vitro Model: Mycobacterium smegmatis PM791; 1772
• In Vitro Model: Mycobacterium smegmatis PM876; 1772
• In Vitro Model: Mycobacterium smegmatis PM939; 1772
• In Vitro Model: Mycobacterium smegmatis PM976; 1772
• In Vitro Model: Mycobacterium tuberculosis PM638; 1773
• In Vitro Model: Mycobacterium tuberculosis PM669; 1773
• In Vitro Model: Mycobacterium tuberculosis PM670; 1773
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Disk diffusion test assay; E-strip test assay
• Mechanism Description: Mycobacteria produce Beta-lactamases and are intrinsically resistant to Beta-lactam antibiotics.The mutants M. tuberculosis PM638 (detablaC1) and M. smegmatis PM759 (detablaS1) showed an increase in susceptibility to Beta-lactam antibiotics.

Key Molecule: Beta-lactamase (BLA) [14], [15]

• 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 HB101; 634468
• In Vitro Model: Escherichia coli JM101; 562
• Experiment for Molecule Alteration: Whole genome sequence assay
• Mechanism Description: Beta-lactamases (Beta-lactamhydrolase, EC 3.5.2.6), responsible for most of the resistance to Beta-lactam antibiotics, are often plasmid mediated.The OXA-1 beta-lactamase gene is part of Tn2603, which is borne on the R plasmid RGN238.

Key Molecule: Beta-lactamase (BLA) [15], [16], [17]

• Molecule Alteration: Missense mutation; p.L76N+p.V84I+p.A184V
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli JM109; 562
• Mechanism Description: The TEM Beta-lactamases are among the best-studied antibiotic resistance enzymes around.TEM-1, the first TEM allele identified, was isolated from penicillin-resistant bacteria in 1963.

Key Molecule: Beta-lactamase (BLA) [15], [16], [17]

• Molecule Alteration: Missense mutation; p.L76N
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli JM109; 562
• Mechanism Description: The TEM Beta-lactamases are among the best-studied antibiotic resistance enzymes around.TEM-1, the first TEM allele identified, was isolated from penicillin-resistant bacteria in 1963.

Key Molecule: Beta-lactamase (BLA) [18]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Pseudomonas aeruginosa infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pseudomonas aeruginosa PAO1; 208964
• Experiment for Molecule Alteration: DNA sequencing and protein assay
• Experiment for Drug Resistance: Disk diffusion assay
• Mechanism Description: P. aeruginosa harbors two naturally encoded Beta-lactamase genes, one of which encodes an inducible cephalosporinase and the other of which encodes a constitutively expressed oxacillinase. OXA-50 is a kind of oxacillinase which lead to drug resistance.

Key Molecule: Aminoglycoside acetyltransferase (AAC) [19]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Vibrio fluvialis infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Vibrio fluvialis H-08942; 676
• Experiment for Molecule Alteration: PCR; DNA sequencing assay; Southern hybridization assay; Cloning and expression assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Aac(3)-Id is a new type of aminoglycoside acetyltransferase gene which causes drug resistance.

Key Molecule: Metallo-beta-lactamase (VIM1) [3]

• 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
• 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: A. xylosoxydans AX22 exhibited broad-spectrum resistance to Beta-lactams and aminoglycosides. The Beta-lactam resistance pattern (including piperacillin, ceftazidime, and carbapenem resistance) was unusual for this species, and the high-level carbapenem resistance suggested the production of an acquired carbapenemase. In fact, carbapenemase activity was detected in a crude extract of AX22 (specific activity, 184 +/- 12 U/mg of protein), and this activity was reduced (>80%) after incubation of the crude extract with 2 mM EDTA, suggesting the presence of a metallo-Beta-lactamase determinant.

Key Molecule: Beta-lactamase (BLA) [15], [20]

• Molecule Alteration: Missense mutation; p.V77A+p.D114N+p.S140A+p.N288D
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Citrobacter freundii strain 2524/96; 546
• In Vitro Model: Citrobacter freundii strain 2525/96; 546
• In Vitro Model: Citrobacter freundii strain 2526/96; 546
• In Vitro Model: Escherichia coli strain 2527/96; 562
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Sequencing has revealed that C. freundii isolates produced a new CTX-M-3 enzyme which is very closely related to the CTX-M-1/MEN-1 Beta-lactamase.

Key Molecule: Imipenem-hydrolyzing beta-lactamase (NMCA) [21]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Enterobacter cloacae infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli strain JM109; 83333
• In Vitro Model: Enterobacter cloacae strain NOR-1; 550
• Experiment for Molecule Alteration: Dideoxynucleotide chain-termination method assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: Here we report a gene encoding a carbapenemase, which was cloned from the chromosome of a clinical isolate of Enterobacter cloacae, strain NOR-1, into pACYC184 plasmid in Escherichia coli. Unlike all the sequenced carbapenemases, which are class B metallo-beta-lactamases, the mature protein (NmcA) is a class A serine beta-lactamase. NmcA shares the highest amino acid identity (50%) with the extended-spectrum class A beta-lactamase MEN-1 from Escherichia coli.

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ABC transporter ATPase subunit (ABCS) [22], [23], [24]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Enterococcus faecalis isolates; 1351
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Multidrug efflux pump extraction, purification, and sequencing showed the distribution of mefA and msrA/msrB efflux pumps.

Key Molecule: Putative ABC transporter ATP-binding component (OTRC) [25]

• 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
• In Vitro Model: Escherichia coli; 668369
• In Vitro Model: Escherichia coli ET12567 (pUZ8002); 562
• In Vitro Model: Streptomyces rimosus M4018; 1927
• In Vitro Model: Streptomyces rimosus SR16; 1927
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: OtrC is a multidrug resistance protein based on an ATP hydrolysis-dependent active efflux mechanism.OtrC is a multidrug resistance protein based on an ATP hydrolysis-dependent active efflux mechanism.

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

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Beta-lactamase (BLA) [26]

• 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 Co227; 562
• In Vitro Model: Escherichia coli Co228; 562
• In Vitro Model: Escherichia coli Co356; 562
• Experiment for Molecule Alteration: PCR; PCR-restriction fragment length polymorphism analysis; Sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Multiple-antibiotic-resistant phenotype is associated with gene mutation and mar locus regulation.

Key Molecule: Beta-lactamase (BLA) [26]

• 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 Co227; 562
• In Vitro Model: Escherichia coli Co228; 562
• In Vitro Model: Escherichia coli Co356; 562
• Experiment for Molecule Alteration: PCR; PCR-restriction fragment length polymorphism analysis; Sequencing assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Multiple-antibiotic-resistant phenotype is associated with gene mutation and mar locus regulation.

Key Molecule: Metallo-beta-lactamase (VIM1) [3]

• 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: Electroporation of Escherichia coli DH5alpha with the purified plasmid preparation yielded ampicillin-resistant transformants which contained a plasmid apparently identical to pAX22 (data not shown). DH5alpha(pAX22) produced carbapenemase activity (specific activity of crude extract, 202 +/- 14 U/mg of protein) and, compared to DH5alpha, exhibited a decreased susceptibility to several Beta-lactams.

Key Molecule: Beta-lactamase (BLA) [12]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Escherichia coli infection [ICD-11: 1A03.0]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli; 668369
• In Vitro Model: Escherichia coli strain HB101; 634468
• In Vitro Model: Escherichia coli strain JC2926; 562
• Experiment for Molecule Alteration: DNA sequencing assay
• Mechanism Description: SHV Beta-lactamases confer resistance to a broad spectrum of Beta-lactam antibiotics and are of great therapeutic concern for infections caused by many species of the family Enterobacteriaceae. SHV-1, the original member of the SHV Beta-lactamase family, is present in most strains of Klebsiella pneumoniae and may be either chromosomally or plasmid mediated. A plasmid-mediated SHV-1 is also commonly found in Escherichia coli and is seen in other genera as well.

Key Molecule: Aminoglycoside 3'-phosphotransferase (A3AP) [27]

• 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 HB101; 634468
• In Vitro Model: Escherichia coli strain JM103; 83333
• In Vitro Model: Bacillus circulans strain; 1397
• In Vitro Model: Streptomyces lividans strain 66; 1200984
• In Vitro Model: Streptomyces lividans strain M180; 1916
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Semi-quantitative phosphocellulose-paper binding assay method assay
• Mechanism Description: The previous demonstration that the APH gene of B. circulans could be expressed in E.coli. These contained a 5.5kb Hind3-digest insert (pCH4) or a 2.7kb Sal1-digest insert (pCH5) at the corresponding site in pBR322. Both these derivatives expressed ampicillin and ribostamycin resistance in E.coli.

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

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: OXA-23 carbapenemase (BLA OXA-23) [28]

• 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.

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

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [10]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Staphylococcus infection [ICD-11: 1B7Y.3]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pseudomonas aeruginosa isolates; 287
• In Vitro Model: Staphylococcus aureus isolates; 1280
• In Vitro Model: Klebsiella pneumoniae isolates; 573
• In Vitro Model: Acinetobacter isolates; 469
• In Vitro Model: Enterobacter cloacae isolates; 550
• Experiment for Drug Resistance: Disk diffusion method assay
• Mechanism Description: Up-regulation of P-glycoprotein led to ampicillin resistance in the staphylococcus infection.

ICD-13: Digestive system diseases

Periodontal disease [ICD-11: DA0C]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Beta-lactamase (Q9X4S7) [13]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Chronic periodontitis [ICD-11: DA0C.Y]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Prevotella nigrescens strain; 28133
• Experiment for Molecule Alteration: PCR
• Experiment for Drug Resistance: Disc diffusion test
• Mechanism Description: Seventy five percent of patients carried two species of beta-lactamase-producing anaerobic bacteria that comprised 9.4% of the total number of cultivable bacteria. Fifty one percent of beta-lactamase-producing strains mainly Prevotella, Porphyromonas, and Bacteroides carried the cfxA gene, whereas none of them carried blaTEM. Further characterization of the cfxA gene showed that 76.7% of these strains carried the cfxA2 gene, 14% carried cfxA3, and 9.3% carried cfxA6. The cfxA6 gene was present in three Prevotella spp. and in one Porphyromonas spp. Strains containing cfxA genes (56%) were resistant to the beta-lactam antibiotics.

Key Molecule: Beta-lactamase (Q9X4S7) [13]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Chronic periodontitis [ICD-11: DA0C.Y]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Porphyromonas gingivalis strain; 837
• Experiment for Molecule Alteration: PCR
• Experiment for Drug Resistance: Disc diffusion test
• Mechanism Description: Seventy five percent of patients carried two species of beta-lactamase-producing anaerobic bacteria that comprised 9.4% of the total number of cultivable bacteria. Fifty one percent of beta-lactamase-producing strains mainly Prevotella, Porphyromonas, and Bacteroides carried the cfxA gene, whereas none of them carried blaTEM. Further characterization of the cfxA gene showed that 76.7% of these strains carried the cfxA2 gene, 14% carried cfxA3, and 9.3% carried cfxA6. The cfxA6 gene was present in three Prevotella spp. and in one Porphyromonas spp. Strains containing cfxA genes (56%) were resistant to the beta-lactam antibiotics.

ICD-16: Genitourinary system diseases

Urinary tract infection [ICD-11: GC08]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Aminoglycoside (3'') (9) adenylyltransferase (AADA) [11]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Urinary tract infection [ICD-11: GC08.1]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli serogroup O11; 1095705
• In Vitro Model: Escherichia coli serogroup O17; 1010800
• In Vitro Model: Escherichia coli serogroup O73; 2170725
• In Vitro Model: 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) [11]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Urinary tract infection [ICD-11: GC08.1]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli serogroup O11; 1095705
• In Vitro Model: Escherichia coli serogroup O17; 1010800
• In Vitro Model: Escherichia coli serogroup O73; 2170725
• In Vitro Model: 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)

Key Molecule: Dihydrofolate reductase (DHFR) [11]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Urinary tract infection [ICD-11: GC08.1]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli serogroup O11; 1095705
• In Vitro Model: Escherichia coli serogroup O17; 1010800
• In Vitro Model: Escherichia coli serogroup O73; 2170725
• In Vitro Model: 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) [11]

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Urinary tract infection [ICD-11: GC08.1]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli serogroup O11; 1095705
• In Vitro Model: Escherichia coli serogroup O17; 1010800
• In Vitro Model: Escherichia coli serogroup O73; 2170725
• In Vitro Model: 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.

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