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.
Highlights
Pneumocystis jirovecii is an atypical opportunistic fungus with lung tropism and worldwide distribution that continues to be one of the major opportunistic pathogens causing severe Pneumocystis pneumonia (PcP) in individuals with acquired immune deficiency syndrome (AIDS) and patients with immunosuppression due to other causes [1].Dihydropteroate synthase (DHPS) is an essential enzyme in the metabolism of P. jirovecii involved in the synthesis of folic acid [2]
A single-center study performed in Spain evaluated HIV-infected patients with PcP from 1998 to 2010 and showed that P. jirovecii harboring DHPS mutations decreased from 33% before HAART was available to 5.5% post HAART [68]
The different geographical prevalence among mutations of the DHPS gene is related to use of sulfa prophylaxis, and in the person-toperson transmission, which could contribute to spreading P. jirovecii that harbors DHPS mutations
Summary
Pneumocystis jirovecii is an atypical opportunistic fungus with lung tropism and worldwide distribution that continues to be one of the major opportunistic pathogens causing severe Pneumocystis pneumonia (PcP) in individuals with acquired immune deficiency syndrome (AIDS) and patients with immunosuppression due to other causes [1]. Widespread prophylaxis and treatment for P. jirovecii with sulfa drugs have decreased the incidence of PcP, but concerns have been raised about the possible emergence of P. jirovecii isolates resistant to these drugs. Point mutations in this gene have been associated with prior exposure to sulfa drugs in other microorganisms [3]. Based on the homology with other microorganisms and studies used heterologous expression, mutations in the DHPS gene at positions 55 (Thr55Ala) and 57 (Pro57Ser) suggest the possibility that in Pneumocystis these polymorphisms might be responsible for some failures of sulfa-drugs prophylaxis in PcP patients [3,4,5]
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