High Prevalence of Dihydropteroate Synthase Mutations in Pneumocystis jirovecii Isolated from Patients with Pneumocystis Pneumonia in South Africa
- 1 June 2010
- journal article
- Published by American Society for Microbiology in Journal of Clinical Microbiology
- Vol. 48 (6), 2016-2021
- https://doi.org/10.1128/jcm.02004-09
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.Keywords
This publication has 41 references indexed in Scilit:
- A Followup Study of Asymptomatic Carriers ofPneumocystis jiroveciDuring Immunosuppressive Therapy for Rheumatoid ArthritisThe Journal of Rheumatology, 2009
- Clinical Significance and Phylogenetic Relationship of Novel Australian Pneumocystis jirovecii GenotypesJournal of Clinical Microbiology, 2009
- Pneumocystis jirovecii pneumonia in Spanish HIV-infected patients in the combined antiretroviral therapy era: prevalence of dihydropteroate synthase mutations and prognostic factors of mortalityDiagnostic Microbiology and Infectious Disease, 2008
- PneumocystisPneumonia in HIV-positive Adults, Malawi1Emerging Infectious Diseases, 2007
- Pneumocystis jiroveci pneumonia and other pulmonary infections in TB smear-negative HIV-positive patients with atypical chest X-ray in EthiopiaScandinavian Journal of Infectious Diseases, 2007
- Prevalence of DHPS Polymorphisms Associated with Sulfa Resistance in South African Pneumocystis jirovecii StrainsThe Journal of Eukaryotic Microbiology, 2006
- Pneumocystis jiroveci Dihydropteroate Synthase Polymorphisms Confer Resistance to Sulfadoxine and Sulfanilamide in Saccharomyces cerevisiaeAntimicrobial Agents and Chemotherapy, 2004
- Mutations in the Dihydropteroate Synthase Gene of Human‐DerivedPneumocystis cariniiIsolates from Italy Are Infrequent but Correlate with Prior Sulfa ProphylaxisThe Journal of Infectious Diseases, 2002
- Antimicrobial Resistance in Streptococcus pneumoniae: Implications for Patients With Community-Acquired PneumoniaMayo Clinic Proceedings, 2000
- Structure and function of the dihydropteroate synthase from staphylococcus aureusJournal of Molecular Biology, 1997