High Prevalence of Dihydropteroate Synthase Mutations in Pneumocystis jirovecii Isolated from Patients with Pneumocystis Pneumonia in South Africa
Pneumocystis jirovecii pneumonia (PCP) is an important cause of morbidity and mortality in immunocompromised patients. Sulfa-containing drugs are used for the treatment and prophylaxis of PCP. Mutations in the P. jirovecii fas gene, which encodes dihydropteroate synthase (DHPS), are associated with...
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Published in | Journal of Clinical Microbiology Vol. 48; no. 6; pp. 2016 - 2021 |
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Abstract | Pneumocystis jirovecii pneumonia (PCP) is an important cause of morbidity and mortality in immunocompromised patients. Sulfa-containing drugs are used for the treatment and prophylaxis of PCP. Mutations in the P. jirovecii fas gene, which encodes dihydropteroate synthase (DHPS), are associated with prior exposure to sulfa drugs, and their appearance suggests the emergence of variants with reduced sulfa susceptibility. The present study examined the prevalence of DHPS mutations in P. jirovecii strains isolated from South African patients with PCP. P. jirovecii infection was investigated by immunofluorescence microscopy and quantitative real-time PCR with respiratory specimens from 712 patients (93% of whom were >15 years of age) with suspected PCP consecutively received for the detection of P. jirovecii over 1 year. PCR amplification and sequencing of the DHPS fas gene was attempted with DNA from the P. jirovecii-positive samples. P. jirovecii infection was confirmed by immunofluorescence microscopy in 168/712 (24%) of the patients. Carriage of the fungus was revealed by real-time PCR in 17% of the patients with negative microscopy results. The P. jirovecii fas gene was successfully amplified from specimens from 151 patients and sequenced. Mutations resulting in the Thr55Ala and/or Pro57Ser amino acid substitution were detected in P. jirovecii strains from 85/151 (56%) patients. The high frequency of PCP episodes with P. jirovecii harboring DHPS mutations in South Africa indicates that populations of this fungus are evolving under the considerable selective pressure exerted by sulfa-containing antibiotics. These results, similar to previous observations of sulfa drug resistance in bacterial populations, underscore the importance of the rational use of sulfa medications either prophylactically against PCP or for the treatment of other infections. |
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Pneumocystis jirovecii pneumonia (PCP) is an important cause of morbidity and mortality in immunocompromised patients. Sulfa-containing drugs are used for the treatment and prophylaxis of PCP. Mutations in the P. jirovecii fas gene, which encodes dihydropteroate synthase (DHPS), are associated with prior exposure to sulfa drugs, and their appearance suggests the emergence of variants with reduced sulfa susceptibility. The present study examined the prevalence of DHPS mutations in P. jirovecii strains isolated from South African patients with PCP. P. jirovecii infection was investigated by immunofluorescence microscopy and quantitative real-time PCR with respiratory specimens from 712 patients (93% of whom were >15 years of age) with suspected PCP consecutively received for the detection of P. jirovecii over 1 year. PCR amplification and sequencing of the DHPS fas gene was attempted with DNA from the P. jirovecii-positive samples. P. jirovecii infection was confirmed by immunofluorescence microscopy in 168/712 (24%) of the patients. Carriage of the fungus was revealed by real-time PCR in 17% of the patients with negative microscopy results. The P. jirovecii fas gene was successfully amplified from specimens from 151 patients and sequenced. Mutations resulting in the Thr55Ala and/or Pro57Ser amino acid substitution were detected in P. jirovecii strains from 85/151 (56%) patients. The high frequency of PCP episodes with P. jirovecii harboring DHPS mutations in South Africa indicates that populations of this fungus are evolving under the considerable selective pressure exerted by sulfa-containing antibiotics. These results, similar to previous observations of sulfa drug resistance in bacterial populations, underscore the importance of the rational use of sulfa medications either prophylactically against PCP or for the treatment of other infections. Pneumocystis jirovecii pneumonia (PCP) is an important cause of morbidity and mortality in immunocompromised patients. Sulfa-containing drugs are used for the treatment and prophylaxis of PCP. Mutations in the P. jirovecii fas gene, which encodes dihydropteroate synthase (DHPS), are associated with prior exposure to sulfa drugs, and their appearance suggests the emergence of variants with reduced sulfa susceptibility. The present study examined the prevalence of DHPS mutations in P. jirovecii strains isolated from South African patients with PCP. P. jirovecii infection was investigated by immunofluorescence microscopy and quantitative real-time PCR with respiratory specimens from 712 patients (93% of whom were >15 years of age) with suspected PCP consecutively received for the detection of P. jirovecii over 1 year. PCR amplification and sequencing of the DHPS fas gene was attempted with DNA from the P. jirovecii -positive samples. P. jirovecii infection was confirmed by immunofluorescence microscopy in 168/712 (24%) of the patients. Carriage of the fungus was revealed by real-time PCR in 17% of the patients with negative microscopy results. The P. jirovecii fas gene was successfully amplified from specimens from 151 patients and sequenced. Mutations resulting in the Thr55Ala and/or Pro57Ser amino acid substitution were detected in P. jirovecii strains from 85/151 (56%) patients. The high frequency of PCP episodes with P. jirovecii harboring DHPS mutations in South Africa indicates that populations of this fungus are evolving under the considerable selective pressure exerted by sulfa-containing antibiotics. These results, similar to previous observations of sulfa drug resistance in bacterial populations, underscore the importance of the rational use of sulfa medications either prophylactically against PCP or for the treatment of other infections. |
Author | Dini, Leigh Frean, John Fernandez, Victor du Plessis, Mignon |
AuthorAffiliation | Department of Parasitology, Mycology, and Environmental Microbiology, Swedish Institute for Infectious Disease Control, Solna, Sweden, 1 School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, South Africa, 2 Respiratory and Meningeal Pathogens Research Unit, National Institute for Communicable Diseases, Johannesburg, South Africa, 3 School of Pathology, University of the Witwatersrand, Johannesburg, South Africa, 4 Parasitology Reference Unit, National Institute for Communicable Diseases, Johannesburg, South Africa 5 |
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Snippet | Pneumocystis jirovecii pneumonia (PCP) is an important cause of morbidity and mortality in immunocompromised patients. Sulfa-containing drugs are used for the... Article Usage Stats Services JCM Citing Articles Google Scholar PubMed Related Content Social Bookmarking CiteULike Delicious Digg Facebook Google+ Mendeley... Pneumocystis jirovecii pneumonia (PCP) is an important cause of morbidity and mortality in immunocompromised patients. Sulfa-containing drugs are used for the... |
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StartPage | 2016 |
SubjectTerms | Adolescent Adult Aged Aged, 80 and over Biological and medical sciences Child Child, Preschool Dihydropteroate Synthase - genetics DNA, Fungal - chemistry DNA, Fungal - genetics Female Fundamental and applied biological sciences. Psychology Fungal Proteins - genetics Humans Infant Male Microbiology Microscopy, Fluorescence Middle Aged Miscellaneous Mutation, Missense Mycology Pneumocystis Pneumocystis carinii - enzymology Pneumocystis carinii - genetics Pneumocystis carinii - isolation & purification Pneumonia, Pneumocystis - microbiology Polymerase Chain Reaction Sequence Analysis, DNA South Africa Sputum - microbiology Young Adult |
Title | High Prevalence of Dihydropteroate Synthase Mutations in Pneumocystis jirovecii Isolated from Patients with Pneumocystis Pneumonia in South Africa |
URI | http://jcm.asm.org/content/48/6/2016.abstract https://www.ncbi.nlm.nih.gov/pubmed/20351205 https://search.proquest.com/docview/733110194 https://search.proquest.com/docview/746082131 https://pubmed.ncbi.nlm.nih.gov/PMC2884465 |
Volume | 48 |
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