Abstract
Pneumocystis jirovecii is an opportunistic fungus occurring in human lungs. The group at highest risk consists of HIV-infected and non-HIV-infected immunosuppressed individuals. In these patients, P. jirovecii infection may lead to Pneumocystis pneumonia; it may, however, persist also in an asymptomatic form. This study aimed to determine the prevalence of P. jirovecii and potential risk factors for infection in a group of renal transplant recipients and to characterize the genetic diversity of this fungus in the studied population. Sputum specimens from 72 patients were tested for presence of P. jirovecii using immunofluorescence microscopy, as well as nested PCR targeting the mtLSU rRNA gene. Genotyping involving analysis of four loci—mtLSU rRNA, CYB, DHPS, and SOD—was used to characterize the diversity of the detected organisms. Pneumocystis DNA was detected in eight (11.11%) patients. It has been shown that low eosinophil count and dual immunosuppressive treatment combining prednisone and calcineurin inhibitors are potential risk factors for colonization. Analysis of genotype distribution showed an association of the wild-type genotype of mtLSU rRNA with lower average age of patients and shorter time after kidney transplantation. Furthermore, CYB 2 genotype was detected only in patients with the ongoing prophylaxis regimen. In conclusion, renal transplant recipients are at risk of Pneumocystis colonization even a long time after transplantation. The present preliminary study identifies specific polymorphisms that appear to be correlated with certain patient characteristics and highlights the need for deeper investigation of these associations in renal transplant recipients.
Highlights
Pneumocystis jirovecii is a unicellular parasitic fungus occurring in the human lower respiratory tract
Persistent fungal colonization may contribute to the selection of drug-resistant genetic variants, for instance due to the application of specific medications in prophylactic treatment. One of such agents is co-trimoxazole, the first choice for prevention and treatment of P. jirovecii infections. This drug is a Parasitol Res (2019) 118:181–189 combination of two components: trimethoprim (TMP) and a sulfa drug, sulfamethoxazole (SMX), active against two enzymes playing a key role in the metabolic pathway of synthesis of folic acid: dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS), respectively (Lobo et al 2013)
It has been suggested that the previous use of sulfa drugs, which are employed in many other disorders, may be associated with the exertion of selective pressure on the emergence of mutations within the DHPS gene (Lane et al 1997)
Summary
Pneumocystis jirovecii is a unicellular parasitic fungus occurring in the human lower respiratory tract. The occurrence of single nucleotide polymorphisms (SNPs) within these genes may result from the influence of various environmental factors. Concurrent analysis of these three loci has a sufficient discriminatory power for epidemiological investigation of Pneumocystis genetic diversity. The DHPS locus can be included in such analysis, especially in patients receiving previous TMP-SMX therapy, as it can provide additional information regarding correlation of mutations within this locus with sulfa drug use and prophylaxis failure. Two SNPs in the Pneumocystis DHPS gene have been described, occurring at the 165 and 171 nucleotide positions These point mutations lead to the altered structure of the enzyme, as they cause amino acid substitutions Thr55Ala and Pro57Ser in the DHPS protein, respectively. The reported prevalence of mutations in the considered loci is variable, depending on factors such as the type of the study group, as well as the geographical location and various prophylaxis regimens used in different countries (Huang et al 2000; Esteves et al 2008; Siripattanapipong et al 2008; Dimonte et al 2013; Suárez et al 2017)
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