Drug Information

Drug (ID: DG00183) and It's Reported Resistant Information

• Name: Amoxicillin
• Synonyms: AMPC; Actimoxi; Amoclen; Amolin; Amopen; Amopenixin; Amoxi; Amoxibiotic; Amoxicaps; Amoxicilina; Amoxicillanyl; Amoxicilline; Amoxicillinum; Amoxiden; Amoxil; Amoxivet; Amoxycillin; Anemolin; Aspenil; Biomox; Bristamox; Cemoxin; Clamoxyl; Delacillin; DisperMox; Efpenix; Flemoxin; Hiconcil; Histocillin; Hydroxyampicillin; Ibiamox; Imacillin; Lamoxy; Larotid; Moxacin; Moxal; Moxatag; Ospamox; Pamoxicillin; Piramox; Polymox; Robamox; Sumox; Tolodina; Trimox; Unicillin; Utimox; Vetramox; Wymox; AMOXICILLIN CRYSTALLINE; AMOXICILLIN PEDIATRIC; Amoxicillin anhydrous; Amoxicilline [INN]; Amoxycillin Trihydrate; Metafarma capsules; Metifarma capsules; Sawamox PM; BLP 1410; AMK (TN); Actimoxi (TN); Alphamox (TN); Amoksibos (TN); Amoksiklav (TN); Amoxi-Mast; Amoxibiotic (TN); Amoxicilina (TN); Amoxicilina [INN-Spanish]; Amoxicillin (INN); Amoxicillin (TN); Amoxicillin (anhydrous); Amoxicilline [INN-French]; Amoxicillinum [INN-Latin]; Amoxiclav (TN); Amoxidal (TN); Amoxil (TN); Amoxin (TN); Apo-Amoxi; Augmentin (TN); BL-P 1410; BRL-2333; Bactox (TN); Betalaktam (TN); Cilamox (TN); Clamoxyl (TN); Curam (TN); D-Amoxicillin; Dedoxil (TN); Dispermox (TN); Duomox (TN); Enhancin (TN); Geramox (TN); Gimalxina (TN); Hiconcil (TN); Isimoxin (TN); Klavox (TN); Lamoxy (TN); Moxatag (TN); Moxilen (TN); Moxypen (TN); Moxyvit (TN); Nobactam (TN); Novamoxin (TN); Ospamox (TN); P-Hydroxyampicillin; Pamoxicillin (TN); Panamox (TN); Panklav (TN); Polymox (TN); Ro 10-8756; Samthongcillin (TN); Sandoz (TN); Senox (TN); Sinacilin (TN); Tolodina (TN); Trimox (TN); Wymox (TN); Yucla (TN); Zerrsox (TN); Zimox (TN); Apo-Amoxi (TN); Alpha-Amino-p-hydroxybenzylpenicillin; D-2-Amino-2-(4-hydroxyphenyl)acetamidopenicillanic acid; D-(-)-alpha-Amino-p-hydroxybenzylpenicillin; (-)-6-(2-Amino-2-(P-hydroxyphenyl)acetamido)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo-(3.2.0)heptane-2-carboxylic acid; (2S,5R,6R)-6-[[(2R)-2-amino-2-(4-hydroxyphenyl)acetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid; (2S,5R,6R)-6-{[(2R)-2-amino-2-(4-hydroxyphenyl)acetyl]amino}-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid; 4-Thia-1-azabicyclo(3.2.0)heptane-2-carboxylic acid, 6-(2-amino-2-(p-hydroxyphenyl)acetamido)-3,3-dimethyl-7-oxo-, D-(8CI); 6-(D-(-)-alpha-Amino-p-hydroxyphenylacetamido)penicillanic acid; 6-(D-(-)-p-Hydroxy-alpha-aminobenzyl)penicillin; 6-(p-Hydroxy-alpha-aminophenylacetamido)penicillanic acid; 6beta-[(2R)-2-amino-2-(4-hydroxyphenyl)acetamido]-2,2-dimethylpenam-3alpha-carbonyl; 6beta-[(2R)-2-amino-2-(4-hydroxyphenyl)acetamido]-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)
  Anaerobic bacterial infection [ICD-11: 1A09]; [3], [4]
  Bacterial infection [ICD-11: 1A00-1C4Z]; [5], [6], [7]
  Gram-negative bacterial infection [ICD-11: 1B74-1G40]; [8], [9]
  Helicobacter pylori infection [ICD-11: DA60]; [10]
  Melioidosis [ICD-11: 1C42]; [11], [12]
  Mycobacterial diseases [ICD-11: 1B2Z ]; [13]
  Periodontal disease [ICD-11: DA0C]; [14]
  Peritoneal cancer [ICD-11: 2C51]; [15]
  Pneumonia [ICD-11: CA40]; [16]
  Reflux esophagitis [ICD-11: DA22]; [17]
  Shigellosis [ICD-11: 1A02]; [18]
  Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (1 diseases)
  Periodontal disease [ICD-11: DA0C]; [19]
• Target: Bacterial Cell membrane (Bact CM); NOUNIPROTAC; [1]
• Formula: C16H19N3O5S
• IsoSMILES: CC1([C@@H](N2[C@H](S1)[C@@H](C2=O)NC(=O)[C@@H](C3=CC=C(C=C3)O)N)C(=O)O)C
• InChI: 1S/C16H19N3O5S/c1-16(2)11(15(23)24)19-13(22)10(14(19)25-16)18-12(21)9(17)7-3-5-8(20)6-4-7/h3-6,9-11,14,20H,17H2,1-2H3,(H,18,21)(H,23,24)/t9-,10-,11+,14-/m1/s1
• InChIKey: LSQZJLSUYDQPKJ-NJBDSQKTSA-N
• PubChem CID: 33613
• ChEBI ID: CHEBI:2676
• TTD Drug ID: D0F6EO
• VARIDT ID: DR00190
• INTEDE ID: DR0104
• DrugBank ID: DB01060

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

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-01: Infectious/parasitic diseases

Anaerobic bacterial infection [ICD-11: 1A00-1A09]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Beta-lactamase (BLA) [3], [4]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Anaerobic Bacterial infection [ICD-11: 1A00-1A09]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli HB101; 634468
• In Vitro Model: Escherichia coli JM109; 562
• In Vitro Model: Acidaminococcus fermentans RYC-MR95; 905
• In Vitro Model: Acidaminococcus fermentans RYC4093; 905
• In Vitro Model: Acidaminococcus fermentans RYC4356; 905
• In Vitro Model: Escherichia coli RYC1000; 562
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay; broth microdilution method assay
• Mechanism Description: A. intestini is the first Gram-negative coccus with demonstrated resistance to beta-lactam antibiotics. The reference genome of the A. intestini strain RyC-MR95, which was isolated from a perianal abscess of a European male diabetic patient, contains the aci1 gene, which encodes the ACI-1 class A beta-lactamase that confers resistance to penicillins and extended-spectrum cephalosporins.

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) [20]

• Molecule Alteration: Missense mutation; p.Y104A+p.N110D+p.E175Q+p.S179A
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli TOP10; 83333
• In Vitro Model: Acinetobacter baumannii CIP70.10; 470
• In Vitro Model: Klebsiella pneumoniae kP3; 1290996
• In Vitro Model: Pseudomonas aeruginosa PU21; 287
• Experiment for Molecule Alteration: Whole genome sequence assay; Allelic frequency measurement assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: K. pneumoniae kP3 was resistant to all Beta-lactams, including carbapenems, and expressed the carbapenem-hydrolyzing Beta-lactamase OXA-181, which differs from OXA-48 by four amino acid substitutions. Compared to OXA-48, OXA-181 possessed a very similar hydrolytic profile.

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) [7], [21]

• 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) [7], [22]

• Molecule Alteration: Missense mutation; p.D240G
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli; 668369
• In Vitro Model: Escherichia coli Gre-1; 562
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: The first extended-spectrum Beta-lactamase (ESBL) of the CTX-M type (MEN-1/CTX-M-1) was reported at the beginning of the 1990s.CTX-M-27 differed from CTX-M-14 only by the substitution D240G and was the third CTX-M enzyme harbouring this mutation after CTX-M-15 and CTX-M-16. The Gly-240-harbouring enzyme CTX-M-27 conferred to Escherichia coli higher MICs of ceftazidime (MIC, 8 versus 1 mg/L) than did the Asp-240-harbouring CTX-M-14 enzyme.

Key Molecule: Beta-lactamase (BLA) [5], [6], [7]

• Molecule Alteration: Missense mutation; p.D240G
• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli DH10B; 316385
• In Vitro Model: Citrobacter freundii 2526/96; 546
• In Vitro Model: Escherichia coli isolates; 562
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: We have reported recently the DNA sequence of another Beta-lactamase, CTX- M-15, from Indian enterobacterial isolates that were resistant to both cefotaxime and ceftazidime.CTX-M-15 has a single amino acid change [Asp-240-Gly (Ambler numbering)]7 compared with CTX-M-3.

Mycobacterial diseases [ICD-11: 1B2Z ]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

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

• Molecule Alteration: Expression; Inherence
• Resistant Disease: Mycobacterium fortuitum infection [ICD-11: 1B2Z.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli strain HB101; 634468
• In Vitro Model: Escherichia coli strain MC1061; 1211845
• In Vitro Model: Escherichia coli strain XL1-Blu9; 562
• In Vitro Model: Mycolicibacterium fortuitum strain D316; 1766
• In Vitro Model: Mycolicibacterium fortuitum strain FC1; 1766
• In Vitro Model: Mycolicibacterium smegmatis strain mc^155; 246196
• Experiment for Molecule Alteration: SDS-polyacrylamide gel assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: The gene encoding a class A (t-lactamase was cloned from a natural Isolate of Mycobacterium fortuitum {blaF) and from a high-level amoxicillJn-resistant mutant that produces large amounts of p-lactamase (blaF*).

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

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Beta-lactamase (BLA) [8], [9]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Gram-negative bacterial infection [ICD-11: 1B74-1G40]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli; 668369
• In Vitro Model: Acinetobacter johnsonii LIM75; 40214
• In Vitro Model: Aeromonas allosaccharophila LIM82; 656
• In Vitro Model: Citrobacter freundii LIM86; 546
• In Vitro Model: Escherichia coli MFDpir; 562
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay; broth microdilution method assay
• Mechanism Description: All known class 3 integrons harbour gene cassettes encoding resistance to Beta-lactams (blaIMP, blaGES, blaBEL, blaOXA-256) and aminoglycosides [aac(6')-Ib].

Melioidosis [ICD-11: 1C42]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Outer membrane porin (OMP38) [11], [12]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Melioidosis [ICD-11: 1C42.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli; 668369
• In Vitro Model: Escherichia coli BL21(DE3); 469008
• In Vitro Model: Burkholderia pseudomallei isolates; 28450
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Broth microdilution method assay
• Mechanism Description: Bps is highly resistant to many antimicrobial agents and this resistance may result from the low drug permeability of outer membrane proteins, known as porins.An Escherichia coli strain defective in most porins, but expressing BpsOmp38, exhibited considerably lower antimicrobial susceptibility than the control strain. In addition, mutation of Tyr119, the most prominent pore-lining residue in BpsOmp38, markedly altered membrane permeability, substitution with Ala (mutant BpsOmp38Y119A) enhanced uptake of the antimicrobial agents, while substitution with Phe (mutant BpsOmp38Y119F) inhibited uptake.

ICD-12: Respiratory system diseases

Pneumonia [ICD-11: CA40]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Penicillin-binding protein 1A (PBP1A) [23]

• Molecule Alteration: Missense mutation; p.S351A
• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Correspondence discriminant assay
• Mechanism Description: The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).

Key Molecule: Penicillin-binding protein 1A (PBP1A) [23]

• Molecule Alteration: Missense mutation; p.S575T
• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Correspondence discriminant assay
• Mechanism Description: The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).

Key Molecule: Penicillin-binding protein 1A (PBP1A) [23]

• Molecule Alteration: Missense mutation; p.N609D
• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Correspondence discriminant assay
• Mechanism Description: The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).

Key Molecule: Penicillin-binding protein 1A (PBP1A) [23]

• Molecule Alteration: Missense mutation; p.E512K
• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Correspondence discriminant assay
• Mechanism Description: The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).

Key Molecule: Penicillin-binding protein 2B (PBP2B) [23]

• Molecule Alteration: Missense mutation; p.T445A
• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Correspondence discriminant assay
• Mechanism Description: The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).

Key Molecule: Penicillin-binding protein 2B (PBP2B) [23]

• Molecule Alteration: Missense mutation; p.E475G
• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Correspondence discriminant assay
• Mechanism Description: The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).

Key Molecule: Penicillin-binding protein 2B (PBP2B) [23]

• Molecule Alteration: Missense mutation; p.T488A
• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Correspondence discriminant assay
• Mechanism Description: The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).

Key Molecule: Penicillin-binding protein 2B (PBP2B) [23]

• Molecule Alteration: Missense mutation; p.A591S
• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Correspondence discriminant assay
• Mechanism Description: The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).

Key Molecule: Penicillin-binding protein 2B (PBP2B) [23]

• Molecule Alteration: Missense mutation; p.G596P
• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Correspondence discriminant assay
• Mechanism Description: The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).

Key Molecule: Penicillin-binding protein 2B (PBP2B) [23]

• Molecule Alteration: Missense mutation; p.N605D
• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Correspondence discriminant assay
• Mechanism Description: The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).

Key Molecule: Penicillin-binding protein 2B (PBP2B) [23]

• Molecule Alteration: Missense mutation; p.L608T
• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Correspondence discriminant assay
• Mechanism Description: The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).

Key Molecule: Penicillin-binding protein 2B (PBP2B) [23]

• Molecule Alteration: Missense mutation; p.G618A
• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Correspondence discriminant assay
• Mechanism Description: The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).

Key Molecule: Penicillin-binding protein 2B (PBP2B) [23]

• Molecule Alteration: Missense mutation; p.D624G
• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Correspondence discriminant assay
• Mechanism Description: The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).

Key Molecule: Penicillin-binding protein 2B (PBP2B) [23]

• Molecule Alteration: Missense mutation; p.Q627E
• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Correspondence discriminant assay
• Mechanism Description: The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).

Key Molecule: Penicillin-binding protein 2B (PBP2B) [23]

• Molecule Alteration: Missense mutation; p.T629N
• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Correspondence discriminant assay
• Mechanism Description: The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).

Key Molecule: Penicillin-binding protein 2X (PBP2X) [23]

• Molecule Alteration: Missense mutation; p.T338A
• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Correspondence discriminant assay
• Mechanism Description: The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).

Key Molecule: Penicillin-binding protein 2X (PBP2X) [23]

• Molecule Alteration: Missense mutation; p.E320K
• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Correspondence discriminant assay
• Mechanism Description: The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).

Key Molecule: Penicillin-binding protein 2X (PBP2X) [23]

• Molecule Alteration: Missense mutation; p.Q552E
• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Correspondence discriminant assay
• Mechanism Description: The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).

Key Molecule: Penicillin-binding protein 2X (PBP2X) [23]

• Molecule Alteration: Missense mutation; p.D311N
• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Correspondence discriminant assay
• Mechanism Description: The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).

Key Molecule: Penicillin-binding protein 2X (PBP2X) [23]

• Molecule Alteration: Missense mutation; p.M343T
• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Correspondence discriminant assay
• Mechanism Description: The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).

Key Molecule: Penicillin-binding protein 2X (PBP2X) [23]

• Molecule Alteration: Missense mutation; p.A491V
• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Correspondence discriminant assay
• Mechanism Description: The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).

Key Molecule: Penicillin-binding protein 2X (PBP2X) [23]

• Molecule Alteration: Missense mutation; p.D506E
• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Correspondence discriminant assay
• Mechanism Description: The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).

Key Molecule: Penicillin-binding protein 2X (PBP2X) [23]

• Molecule Alteration: Missense mutation; p.T536I
• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Correspondence discriminant assay
• Mechanism Description: The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).

Key Molecule: Penicillin-binding protein 2X (PBP2X) [23]

• Molecule Alteration: Missense mutation; p.V641I
• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Correspondence discriminant assay
• Mechanism Description: The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).

Key Molecule: Penicillin-binding protein 2X (PBP2X) [23]

• Molecule Alteration: Missense mutation; p.L657I
• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Correspondence discriminant assay
• Mechanism Description: The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).

Key Molecule: Penicillin-binding protein 2X (PBP2X) [23]

• Molecule Alteration: Missense mutation; p.A693V
• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Correspondence discriminant assay
• Mechanism Description: The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).

Key Molecule: Penicillin-binding protein 2X (PBP2X) [23]

• Molecule Alteration: Missense mutation; p.T703K
• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Correspondence discriminant assay
• Mechanism Description: The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).

Key Molecule: Penicillin-binding protein 2X (PBP2X) [23]

• Molecule Alteration: Missense mutation; p.L710F
• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Correspondence discriminant assay
• Mechanism Description: The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).

Key Molecule: Penicillin-binding protein 2X (PBP2X) [23]

• Molecule Alteration: Missense mutation; p.D740N
• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Correspondence discriminant assay
• Mechanism Description: The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).

Key Molecule: Penicillin-binding protein 2X (PBP2X) [23]

• Molecule Alteration: Missense mutation; p.T745K
• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Correspondence discriminant assay
• Mechanism Description: The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).

Key Molecule: Penicillin-binding protein 2X (PBP2X) [23]

• Molecule Alteration: Missense mutation; p.Q629K
• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Correspondence discriminant assay
• Mechanism Description: The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).

Key Molecule: Penicillin-binding protein 2X (PBP2X) [23]

• Molecule Alteration: Missense mutation; p.Q632T
• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Correspondence discriminant assay
• Mechanism Description: The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Bcr/CflA family efflux transporter (BCML) [16]

• 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 DH10B; 316385
• In Vitro Model: Escherichia coli strain NCTC 50192; 562
• In Vitro Model: Klebsiella pneumoniae strain ORI-1; 573
• Experiment for Molecule Alteration: PCR and hybridization experiments assay
• Experiment for Drug Resistance: Agar dilution technique assay
• Mechanism Description: Klebsiella pneumoniae ORI-1 strain harbored a ca. 140-kb nontransferable plasmid, pTk1, that conferred an extended-spectrum cephalosporin resistance profile antagonized by the addition of clavulanic acid, tazobactam, or imipenem. The gene for GES-1 (Guiana extended-spectrum beta-lactamase) was cloned, and its protein was expressed in Escherichia coli DH10B, where this pI-5. 8 beta-lactamase of a ca. 31-kDa molecular mass conferred resistance to oxyimino cephalosporins (mostly to ceftazidime). GES-1 is weakly related to the other plasmid-located Ambler class A extended-spectrum beta-lactamases (ESBLs).

Key Molecule: Bcr/CflA family efflux transporter (BCML) [16]

• Molecule Alteration: Expression; Acquired
• Resistant Disease: Klebsiella pneumoniae infection [ICD-11: CA40.1]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli DH10B; 316385
• In Vitro Model: Escherichia coli strain NCTC 50192; 562
• In Vitro Model: Klebsiella pneumoniae strain ORI-1; 573
• Experiment for Molecule Alteration: PCR and hybridization experiments assay
• Experiment for Drug Resistance: Agar dilution technique assay
• Mechanism Description: Beta-Lactam MICs for k. pneumoniae ORI-1 and Escherichia coli DH10B harboring either the natural plasmid pTk1 or the recombinant plasmid pC1 were somewhat similar and might indicate the presence of an ESBL. In all cases, the ceftazidime MICs were higher than those of cefotaxime and aztreonam. Beta-Lactam MICs were always lowered by the addition of clavulanic acid or tazobactam, less so by sulbactam, and uncommonly by imipenem.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Bcr/CflA family efflux transporter (BCML) [16]

• Molecule Alteration: Expression; Antagonism
• Sensitive Disease: Klebsiella pneumoniae infection [ICD-11: CA40.1]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli DH10B; 316385
• In Vitro Model: Escherichia coli strain NCTC 50192; 562
• In Vitro Model: Klebsiella pneumoniae strain ORI-1; 573
• Experiment for Molecule Alteration: PCR and hybridization experiments assay
• Experiment for Drug Resistance: Agar dilution technique assay
• Mechanism Description: Inhibition studies, as measured by IC50 values with benzylpenicillin as the substrate, showed that GES-1 was inhibited by clavulanic acid (5 uM) and tazobactam (2.5 uM) and strongly inhibited by imipenem (0.1 uM). Beta-Lactam MICs were always lowered by the addition of clavulanic acid or tazobactam, less so by sulbactam, and uncommonly by imipenem.

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) [19]

• 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) [19]

• 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.

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