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Selection of Pneumocystis jirovecii Inosine 5′-Monophosphate Dehydrogenase Mutants in Solid Organ Transplant Recipients: Implication of Mycophenolic Acid
- Source :
- Journal of Fungi, Vol 7, Iss 849, p 849 (2021), Journal of Fungi, Volume 7, Issue 10, Journal of Fungi, MDPI, 2021, 7 (10), pp.849. ⟨10.3390/jof7100849⟩
- Publication Year :
- 2021
- Publisher :
- MDPI AG, 2021.
-
Abstract
- Mycophenolic acid (MPA) targets the inosine 5′-monophosphate dehydrogenase (IMPDH) of human lymphocytes. It is widely used as an immunosuppressant to prevent rejection in solid organ transplant (SOT) recipients who, incidentally, are at risk for Pneumocystis pneumonia (PCP). We hypothesized that MPA exerts selective pressure on P. jirovecii microorganisms considering its in vitro antifungal activity on other fungi. Thus, we analysed impdh gene in P. jirovecii isolates from SOT recipients. P. jirovecii specimens from 26 patients diagnosed with PCP from 2010 to 2020 were retrospectively examined: 10 SOT recipients treated with MPA and 16 non-SOT patients without prior exposure to MPA. The P. jirovecii impdh gene was amplified and sequenced. Nucleotide sequences were aligned with the reference sequences retrieved from available P. jirovecii whole genomes. The deduced IMPDH protein sequences were aligned with available IMPDH proteins from Pneumocystis spp. and other fungal species known to be in vitro sensitive or resistant to MPA. A total of nine SNPs was identified. One SNP (G1020A) that results in an Ala261Thr substitution was identified in all SOT recipients and in none of the non-SOT patients. Considering that IMPDHs of other fungi, resistant to MPA, harbour Thr (or Ser) at the analogous position, the Ala261Thr mutation observed in MPA-treated patients was considered to represent the signature of P. jirovecii exposure to MPA. These results suggest that MPA may be involved in the selection of specific P. jirovecii strains that circulate in the SOT recipient population.
- Subjects :
- Microbiology (medical)
QH301-705.5
[SDV]Life Sciences [q-bio]
Population
selection
Plant Science
Pneumocystis pneumonia
Mycophenolic acid
Article
Pneumocystis jirovecii
Microbiology
IMPDH
03 medical and health sciences
parasitic diseases
medicine
Inosine-5′-monophosphate dehydrogenase
Biology (General)
education
Inosine
Gene
Ecology, Evolution, Behavior and Systematics
030304 developmental biology
0303 health sciences
education.field_of_study
biology
030306 microbiology
medicine.disease
biology.organism_classification
3. Good health
Transplantation
biology.protein
mycophenolic acid
medicine.drug
transplantation
Subjects
Details
- Language :
- English
- ISSN :
- 2309608X
- Volume :
- 7
- Issue :
- 849
- Database :
- OpenAIRE
- Journal :
- Journal of Fungi
- Accession number :
- edsair.doi.dedup.....2b3603b933dee9a4ba6351bb9d9a94e3
- Full Text :
- https://doi.org/10.3390/jof7100849⟩