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Update on Dihydropteroate Synthase (DHPS) Mutations in Pneumocystis jirovecii
Carmen de la Horra1, Vicente Friaza1,2, Rubén Morilla1,3
1Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Científicas/Universidad de Sevilla, 41013 Seville, Spain.
Abstract:
A Pneumocystis jirovecii is one of the most important microorganisms that cause pneumonia in immunosupressed individuals. The guideline for treatment and prophylaxis of Pneumocystis pneumonia (PcP) is the use of a combination of sulfa drug-containing trimethroprim and sulfamethoxazole. In the absence of a reliable method to culture Pneumocystis, molecular techniques have been developed to detect mutations in the dihydropteroate synthase gene, the target of sulfa drugs, where mutations are related to sulfa resistance in other microorganisms. The presence of dihydropteroate synthase (DHPS) mutations has been described at codon 55 and 57 and found almost around the world. In the current work, we analyzed the most common methods to identify these mutations, their geographical distribution around the world, and their clinical implications. In addition, we describe new emerging DHPS mutations. Other aspects, such as the possibility of transmitting Pneumocystis mutated organisms between susceptible patients is also described, as well as a brief summary of approaches to study these mutations in a heterologous expression system.
Insights
Pneumocystis pneumonia (PcP) treatment relies on sulfa drugs, but mutations in the dihydropteroate synthase (DHPS) gene can cause resistance. This study reviews methods to detect these DHPS mutations, their global spread, and clinical impact.
Area of Science:
- Medical Mycology
- Molecular Biology
- Infectious Diseases
Background:
- Pneumocystis jirovecii is a major cause of pneumonia in immunocompromised individuals.
- Current treatment and prophylaxis for Pneumocystis pneumonia (PcP) involve trimethoprim-sulfamethoxazole, a sulfa drug combination.
- Sulfa drug resistance in microorganisms is often linked to mutations in the dihydropteroate synthase (DHPS) gene.
Purpose of the Study:
- To analyze common methods for identifying DHPS mutations in Pneumocystis jirovecii.
- To review the geographical distribution and clinical implications of these mutations.
- To describe emerging DHPS mutations and discuss transmission possibilities.
Main Methods:
- Review of molecular techniques for detecting DHPS gene mutations.
- Analysis of published data on mutation prevalence and geographical distribution.
- Discussion of heterologous expression systems for studying mutation effects.
Main Results:
- DHPS mutations at codons 55 and 57 are prevalent globally.
- These mutations are associated with sulfa drug resistance in Pneumocystis jirovecii.
- New emerging mutations and potential transmission routes are identified.
Conclusions:
- Molecular detection of DHPS mutations is crucial for understanding and managing PcP.
- Awareness of mutation prevalence and geographical distribution aids treatment strategies.
- Further research into novel mutations and transmission is warranted.
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