Molecule Information

General Information of the Molecule (ID: Mol00893)

• Name: Dihydrofolate reductase (DHFR) ,Pneumocystis jirovecii
• Molecule Type: Protein
• Gene Name: DHFR
• Sequence:
  MDWQKSLTLIVALTLSRGIGLKNDLPWKLKSDMMFFSRVTSGLLVTRSTGQMNVVLMGRK
  TWESLPAHSRPLKNRINVVISRQEVLDLGGGAYHARSLDDALALLSQIYDSTSKIQLNRV
  FVIGGGELYKAAMEHSRLNRIIATVIHNEVDCDVFFPIDFRSSQSCLPWRKQDHSVLEAW
  VGSKVPQGKINENGFIYEFEMWIRDI
• Uniprot ID: Q9UUP5_PNEJI

Kingdom: Fungi
Phylum: Ascomycota
Class: Pneumocystidomycetes
Order: Pneumocystidales
Family: Pneumocystidaceae
Genus: Pneumocystis
Species: Pneumocystis jirovecii

Type(s) of Resistant Mechanism of This Molecule

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Drug

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

Co-trimoxazole

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Pneumocystis jirovecii infection [1]

• Resistant Disease: Pneumocystis jirovecii infection [ICD-11: CA40.6]
• Resistant Drug: Co-trimoxazole
• Molecule Alteration: Missense mutation; p.T55A
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pneumocytis jirovecii strain; 42068
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Multivariate analysis of overall survival or disease-free survival assay
• Mechanism Description: In these 5 resistance-fungal isolates and an additional 8 from consecutive cases of PCP, all strains harbored mutant dhps haplotypes; all 13 isolates harbored the P57S mutation in dhps, and 3 (23%) also harbored the T55A mutation.

Disease Class: Pneumocystis jirovecii infection [1]

• Resistant Disease: Pneumocystis jirovecii infection [ICD-11: CA40.6]
• Resistant Drug: Co-trimoxazole
• Molecule Alteration: Missense mutation; p.P57S
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pneumocytis jirovecii strain; 42068
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Multivariate analysis of overall survival or disease-free survival assay
• Mechanism Description: In these 5 resistance-fungal isolates and an additional 8 from consecutive cases of PCP, all strains harbored mutant dhps haplotypes; all 13 isolates harbored the P57S mutation in dhps, and 3 (23%) also harbored the T55A mutation.

Disease Class: Pneumocystis jirovecii infection [1]

• Resistant Disease: Pneumocystis jirovecii infection [ICD-11: CA40.6]
• Resistant Drug: Co-trimoxazole
• Molecule Alteration: Missense mutation; p.T55A+p.P57S
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pneumocytis jirovecii strain; 42068
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Multivariate analysis of overall survival or disease-free survival assay
• Mechanism Description: In these 5 resistance-fungal isolates and an additional 8 from consecutive cases of PCP, all strains harbored mutant dhps haplotypes; all 13 isolates harbored the P57S mutation in dhps, and 3 (23%) also harbored the T55A mutation.

Disease Class: HIV-infected Pneumocystis pneumonia [2]

• Resistant Disease: HIV-infected Pneumocystis pneumonia [ICD-11: 1C60.1]
• Resistant Drug: Co-trimoxazole
• Molecule Alteration: Missense mutation; p.V96I
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pneumocystis jirovecii isolates; 42068
• Experiment for Molecule Alteration: nested PCR
• Mechanism Description: Among the 76 enrolled HIV-positive patients, only 17 (22.4%) were positive for P. jirovecii. DHPS gene sequencing showed a novel nucleotide substitution at position 288 (Val96Ile) in three patients (3/12; 25.0%). Patients infected with the mutant P. jirovecii genotype had severe episodes of PCP, did not respond to SXT and had a fatal outcome.

References

• Ref 1: Low prevalence of Pneumocystis pneumonia (PCP) but high prevalence of pneumocystis dihydropteroate synthase (dhps) gene mutations in HIV-infected persons in Uganda. PLoS One. 2012;7(11):e49991. doi: 10.1371/journal.pone.0049991. Epub 2012 Nov 16.
• Ref 2: Novel dihydropteroate synthase gene mutation in Pneumocystis jirovecii among HIV-infected patients in India: Putative association with drug resistance and mortality .J Glob Antimicrob Resist. 2019 Jun;17:236-239. doi: 10.1016/j.jgar.2019.01.007. Epub 2019 Jan 15. 10.1016/j.jgar.2019.01.007