Abstract：
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.
The mutations C431T (Ala144Val) and C823T (Leu275Phe) at the cytochrome b (CYB) active site of Pneumocystis jirovecii are associated with patient prior exposure to atovaquone. Conversely, these mutations are incidental in the absence of exposure. Overall, the presence of P. jirovecii CYB mutants remains low in France.
The mutations C431T (Ala144Val) and C823T (Leu275Phe) at the cytochrome b (CYB) active site of Pneumocystis jirovecii are associated with patient prior exposure to atovaquone. Conversely, these mutations are incidental in the absence of exposure. Overall, the presence of P. jirovecii CYB mutants remains low in France.
摘要：
肺孢子虫是一种传染性真菌，可在免疫功能低下的患者中引起严重肺炎（肺孢子虫肺炎[PCP]）。已在P.jirovecii的细胞色素b（CYB）基因上鉴定出归因于atovaquone选择压力的错义突变。最近表明，在器官移植受者中，预防阿托伐酮可导致选择对阿托伐酮具有潜在抗性的特定P.jirovecii细胞色素b突变体。在这种情况下，我们的目的是提供有关P.jirovecii细胞色素b突变体的数据以及atovaquone对法国P.jirovecii生物施加的假定选择压力。回顾性研究了来自四家大都市医院和两家海外医院的123例患者（124例P.jirovecii标本）。14名患者先前曾接触过atovaquone，而109名患者则没有，在检测到P.jirovecii的时候.扩增并测序了吉罗韦氏疟原虫CYB基因的638个碱基对片段。总共鉴定了10个SNP。错义突变C431T（Ala144Val）和C823T（Leu275Phe）都位于该酶的Qo活性位点，与先前的atovaquone暴露显着相关，这些突变在之前没有阿托瓦醌暴露的情况下是偶然的(P<0.001).考虑到上述医院可能代表国家领土，这些发现表明，在法国，P.jirovecii细胞色素b突变体的总体存在仍然很低。
吉罗韦西氏疟原虫细胞色素b活性位点的突变C431T(Ala144Val)和C823T(Leu275Phe)与暴露于阿托伐喹之前的患者相关。相反，这些突变在没有暴露的情况下是偶然的。在法国，P.jirovecii细胞色素b突变体的总体存在仍然很低。
吉罗韦西氏疟原虫细胞色素b活性位点的突变C431T(Ala144Val)和C823T(Leu275Phe)与暴露于阿托伐喹之前的患者相关。相反，这些突变在没有暴露的情况下是偶然的。在法国，P.jirovecii细胞色素b突变体的总体存在仍然很低。
