Laboratoire de Parasitologie et Mycologie, Hôpital de La Cavale Blanche, CHU de Brest, Brest, France.
Université d'Angers, Université de Brest, Groupe d'Étude des Interactions Hôte-Pathogène (GEIHP), France.
Antimicrob Agents Chemother. 2022 Jan 18;66(1):e0156321. doi: 10.1128/AAC.01563-21. Epub 2021 Nov 1.
Echinocandins are noncompetitive inhibitors of the GSC1 subunit of the enzymatic complex involved in synthesis of 1,3-beta-d-glucan, a cell wall component of most fungi, including Pneumocystis spp. Echinocandins are widely used for treating systemic candidiasis and rarely used for treating Pneumocystis pneumonia. Consequently, data on gene diversity are still scarce compared to that for the homologous gene of spp. In this study, we analyzed gene diversity and the putative selection pressure of echinocandins on gene sequences of specimens from two patient groups were compared. One group of 27 patients had prior exposure to echinocandins, whereas the second group of 24 patients did not, at the time of infection diagnoses. Two portions of the gene, HS1 and HS2, homologous to hot spots described in spp., were sequenced. Three single-nucleotide polymorphisms (SNPs) at positions 2204, 2243, and 2303 close to the HS1 region and another SNP at position 4540 more distant from the HS2 region were identified. These SNPs represent synonymous mutations. Three HS1 alleles, A, B, and C, and two HS2 alleles, a and b, and four haplotypes, Ca, Cb, Aa, and Ba, were defined, without significant difference in haplotype distribution in both patient groups (0.57). Considering the identical diversity of gene and the detection of synonymous mutations in both patient groups, no selection pressure of echinocandins among microorganisms can be pointed out so far.
棘白菌素类是参与合成 1,3-β-d-葡聚糖的酶复合物 GSC1 亚基的非竞争性抑制剂,1,3-β-d-葡聚糖是大多数真菌(包括肺孢子菌属)细胞壁的组成部分。棘白菌素类被广泛用于治疗系统性念珠菌病,很少用于治疗肺孢子菌肺炎。因此,与 spp. 的同源基因相比,棘白菌素类对基因多样性的数据仍然很少。在这项研究中,我们分析了棘白菌素类对基因序列的潜在选择压力,并比较了两组患者的基因多样性。一组 27 例患者在感染诊断时曾暴露于棘白菌素类,而另一组 24 例患者则没有。我们对与 spp. 中描述的热点同源的基因的 HS1 和 HS2 两个部分进行了测序。在靠近 HS1 区域的位置 2204、2243 和 2303 以及距离 HS2 区域更远的位置 4540 处发现了三个单核苷酸多态性(SNPs)。这些 SNPs 代表同义突变。我们确定了三个 HS1 等位基因 A、B 和 C 以及两个 HS2 等位基因 a 和 b,以及四个单倍型 Ca、Cb、Aa 和 Ba,两组患者的单倍型分布无显著差异(0.57)。考虑到基因的相同多样性以及两组患者中均检测到同义突变,棘白菌素类对微生物的选择压力目前还无法指出。