Molecule Information

General Information of the Molecule (ID: Mol00901)

• Name: Dihydrofolate reductase (DHFR) ,Streptococcus pyogenes
• Synonyms: DHPS; Dihydropteroate pyrophosphorylase
• Molecule Type: Protein
• Gene Name: folP
• Sequence:
  MKIGKFVIDGNAAIMGILNVTPDSFSDGGSYTTVQKVLQQVDQLIAGGAKIIDVGGESTR
  PGYQFVSAADEIERVVPMIKAIKAKYDVLISIDTYKTETARAALEAGADILNDVRAGLYD
  GEMLALAAEYDVPIILMHNQKEEVYQDVTQDVCDFLSARAQAAIDAGVPKDNIWIDPGFG
  FPKSVQHNMELLKGLDHVCQLGYPVLFGISRKGVVDALLGGNTKAKERDGATAALSAYAL
  GKGCQLVRVHDVKANQEIVAVLSQLM
• Function: Catalyzes the condensation of para-aminobenzoate (pABA) with 6-hydroxymethyl-7,8-dihydropterin diphosphate (DHPt-PP) to form 7,8-dihydropteroate (H2Pte), the immediate precursor of folate derivatives.
• Uniprot ID: DHPS_STRPY

Kingdom: N.A.
Phylum: Firmicutes
Class: Bacilli
Order: Lactobacillales
Family: Streptococcaceae
Genus: Streptococcus
Species: Streptococcus pyogenes

Type(s) of Resistant Mechanism of This Molecule

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Drug

Investigative Drug(s) 1 drug(s) in total

Sulfisomidine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Streptococcus pyogenes infection [1]

• Resistant Disease: Streptococcus pyogenes infection [ICD-11: 1A00-1C4Z]
• Resistant Drug: Sulfisomidine
• Molecule Alteration: Missense mutation; p.E9D+p.A37V+p.D39Q+p.H40Q+p.E42D+p.M44L+p.D47G+p.C63Y+p.T69A+p.D73E+p.V78M+p.E84A+p.N85K+p.I88V+p.W115R+p.Q122E+p.F124L+p.A132V+p.D141K+p.E147D+p.G157S+p.N158A+p.L164I+p.K171D+p.A182P+p.Q187H+p.R197H+p.R213G+p.I246L+p.D257E
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Streptococcus pyogenes strain G1; 1314
• In Vitro Model: Streptococcus pyogenes strain G2; 1314
• In Vitro Model: Streptococcus pyogenes strain G52; 1314
• In Vitro Model: Streptococcus pyogenes strain G56; 1314
• In Vitro Model: Streptococcus pyogenes strain G68; 1314
• In Vitro Model: Streptococcus pyogenes strain G71; 1314
• In Vitro Model: Streptococcus pyogenes strain G72; 1314
• In Vitro Model: Streptococcus pyogenes strain G76; 1314
• Experiment for Molecule Alteration: Dideoxy-chain termination method assay
• Mechanism Description: Sulfonamide resistance in recent isolates of Streptococcus pyogenes was found to be associated with alterations of the chromosomally encoded dihydropteroate synthase (DHPS). There were 111 different nucleotides (13.8%) in the genes found in susceptible and resistant isolates, respectively, resulting in 30 amino acid changes (11.3%).

Disease Class: Streptococcus pyogenes infection [1]

• Resistant Disease: Streptococcus pyogenes infection [ICD-11: 1A00-1C4Z]
• Resistant Drug: Sulfisomidine
• Molecule Alteration: Missense mutation; p.I8V+p.N11K+p.D39Q+p.H40Q+p.E42D+p.M44L+p.D47G+p.C63Y+p.T69A+p.D73E+p.V78M+p.K80I+p.E84A+p.N85K+p.I88V+p.Q122E+p.F124L+p.A132V+p.D141K+p.E147D+p.G157S+p.N158A+p.L164I+p.K171D+p.Q187H+p.R213G+p.V214I+p.I246L+p.D257E
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Streptococcus pyogenes strain G1; 1314
• In Vitro Model: Streptococcus pyogenes strain G2; 1314
• In Vitro Model: Streptococcus pyogenes strain G52; 1314
• In Vitro Model: Streptococcus pyogenes strain G56; 1314
• In Vitro Model: Streptococcus pyogenes strain G68; 1314
• In Vitro Model: Streptococcus pyogenes strain G71; 1314
• In Vitro Model: Streptococcus pyogenes strain G72; 1314
• In Vitro Model: Streptococcus pyogenes strain G76; 1314
• Experiment for Molecule Alteration: Dideoxy-chain termination method assay
• Mechanism Description: Sulfonamide resistance in recent isolates of Streptococcus pyogenes was found to be associated with alterations of the chromosomally encoded dihydropteroate synthase (DHPS). There were 111 different nucleotides (13.8%) in the genes found in susceptible and resistant isolates, respectively, resulting in 30 amino acid changes (11.3%).

References

• Ref 1: Sulfonamide resistance in Streptococcus pyogenes is associated with differences in the amino acid sequence of its chromosomal dihydropteroate synthase. Antimicrob Agents Chemother. 1998 May;42(5):1062-7. doi: 10.1128/AAC.42.5.1062.