Laboratory of Parasitology and Mycology, Brest University Hospital, 29609 Brest, France.
Fungal Respiratory Infections Research Unit (FRI), University of Angers, University of Western Brittany, 29238 Brest, France.
Med Mycol. 2023 Sep 4;61(9). doi: 10.1093/mmy/myad095.
Pneumocystis jirovecii is a transmissible fungus responsible for severe pneumonia (Pneumocystis pneumonia [PCP]) in immunocompromised patients. Missense mutations due to atovaquone selective pressure have been identified on cytochrome b (CYB) gene of P. jirovecii. It was recently shown that atovaquone prophylaxis can lead to the selection of specific P. jirovecii CYB mutants potentially resistant to atovaquone among organ transplant recipients. In this context, our objectives were to provide data on P. jirovecii CYB mutants and the putative selective pressure exerted by atovaquone on P. jirovecii organisms in France. A total of 123 patients (124 P. jirovecii specimens) from four metropolitan hospitals and two overseas hospitals were retrospectively enrolled. Fourteen patients had prior exposure to atovaquone, whereas 109 patients did not at the time of P. jirovecii detection. A 638 base-pair fragment of the CYB gene of P. jirovecii was amplified and sequenced. A total of 10 single nucleotide polymorphisms (SNPs) were identified. Both missense mutations C431T (Ala144Val) and C823T (Leu275Phe), located at the Qo active site of the enzyme, were significantly associated with prior atovaquone exposure, these mutations being conversely incidental in the absence of prior atovaquone exposure (P < 0.001). Considering that the aforementioned hospitals may be representative of the national territory, these findings suggest that the overall presence of P. jirovecii CYB mutants remains low in France.
肺孢子菌是一种可传播的真菌，可导致免疫功能低下的患者发生严重肺炎（肺孢子菌肺炎[PCP]）。在肺孢子菌的细胞色素 b（CYB）基因上已经发现了由于阿托伐醌的选择压力而导致的错义突变。最近的研究表明，阿托伐醌预防可能会导致肺孢子菌 CYB 特定突变体的选择，这些突变体可能对器官移植受者中的阿托伐醌产生耐药性。在这种情况下，我们的目标是提供法国肺孢子菌 CYB 突变体的数据以及阿托伐醌对肺孢子菌产生的潜在选择压力。回顾性纳入了来自四家大都市医院和两家海外医院的 123 名患者（124 份肺孢子菌标本）。14 名患者曾接触过阿托伐醌，而 109 名患者在检测到肺孢子菌时未接触过阿托伐醌。扩增并测序了肺孢子菌 CYB 基因的 638 个碱基对片段。共鉴定出 10 个单核苷酸多态性（SNP）。位于酶的 Qo 活性部位的错义突变 C431T（Ala144Val）和 C823T（Leu275Phe）均与先前接触阿托伐醌显著相关，而在没有先前接触阿托伐醌的情况下，这些突变则是偶然发生的（P<0.001）。考虑到上述医院可能代表全国范围，这些发现表明法国肺孢子菌 CYB 突变体的总体存在仍然较低。
