Amity Institute of Biotechnology, Amity University Haryana, Panchgaon, Manesar, Gurugram, Haryana, India.
Amity Institute of Integrative Sciences and Health, Amity University Haryana, Panchgaon, Manesar, Gurugram, Haryana, India.
Appl Microbiol Biotechnol. 2022 Jun;106(11):4223-4235. doi: 10.1007/s00253-022-11998-9. Epub 2022 Jun 1.
The peptide transport (PTR) or proton-dependent oligopeptide transporter (POT) family exploits the inwardly directed proton motive force to facilitate the cellular uptake of di/tripeptides. Interestingly, some representatives are also shown to import peptide-based antifungals in certain Candida species. Thus, the identification and characterization of PTR transporters serve as an essential first step for their potential usage as antifungal peptide uptake systems. Herein, we present a genome-wide inventory of the PTR transporters in five prominent Candida species. Our study identifies 2 PTR transporters each in C. albicans and C. dubliniensis, 1 in C. glabrata, 4 in C. parapsilosis, and 3 in C. auris. Notably, despite all representatives retaining the conserved features seen in the PTR family, there exist two distinct classes of PTR transporters that differ in terms of their sequence identities and lengths of certain extracellular and intracellular segments. Further, we also evaluated the contribution of each PTR protein of the newly emerged multi-drug-resistant C. auris in di/tripeptide uptake. Notably, deletion of two PTR genes BNJ08_003830 and BNJ08_005124 led to a marked reduction in the transport capabilities of several tested di/tripeptides. However, all three genes could complement the role of native PTR2 gene of Saccharomyces cerevisiae, albeit to varied levels. Besides, BNJ08_005124 deletion also resulted in increased resistance toward the peptide-nucleoside drug Nikkomycin Z as well as the glucosamine-6-phosphate synthase inhibitor, L-norvalyl-N3-(4-methoxyfumaroyl)-L-2,3-diaminopropionoic acid (Nva-FMDP), pointing toward its predominant role in their uptake mechanism. Altogether, the study provides an important template for future structure-function investigations of PTR transporters in Candida species. KEY POINTS: • Candida genome encodes for two distinct classes of PTR transporters. • Candida auris encodes for 3 PTR transporters with different specificities. • BNJ08_005124 in C. auris is involved in the uptake of Nikkomycin Z and Nva-FMDP.
该肽转运体（PTR）或质子依赖的寡肽转运体（POT）家族利用内向质子动力势促进二/三肽的细胞摄取。有趣的是，一些代表还被证明能够在某些假丝酵母物种中输入基于肽的抗真菌药物。因此，鉴定和表征 PTR 转运体是将其作为潜在的抗真菌肽摄取系统使用的重要第一步。在此，我们在五个主要的假丝酵母物种中进行了 PTR 转运体的全基因组清单。我们的研究在 C. albicans 和 C. dubliniensis 中各鉴定出 2 个 PTR 转运体，在 C. glabrata 中鉴定出 1 个，在 C. parapsilosis 中鉴定出 4 个，在 C. auris 中鉴定出 3 个。值得注意的是，尽管所有代表都保留了 PTR 家族中看到的保守特征，但存在两种不同类别的 PTR 转运体，它们在序列同一性和某些细胞外和细胞内片段的长度方面存在差异。此外，我们还评估了新出现的多药耐药性 C. auris 中每个 PTR 蛋白对二/三肽摄取的贡献。值得注意的是，BNJ08_003830 和 BNJ08_005124 两个 PTR 基因的缺失导致几种测试的二/三肽的转运能力显著降低。然而，所有三个基因都可以补充酿酒酵母天然 PTR2 基因的作用，尽管程度不同。此外，BNJ08_005124 的缺失也导致对肽核苷药物 Nikkomycin Z 和葡萄糖胺-6-磷酸合酶抑制剂 L-正缬氨酸-N3-(4-甲氧基富马酰基)-L-2,3-二氨基丙氨酸（Nva-FMDP）的抗性增加，表明其在摄取机制中的主要作用。总之，该研究为未来假丝酵母属 PTR 转运体的结构功能研究提供了重要模板。 要点： • 假丝酵母基因组编码两种不同类别的 PTR 转运体。 • C. auris 编码具有不同特异性的 3 种 PTR 转运体。 • C. auris 中的 BNJ08_005124 参与 Nikkomycin Z 和 Nva-FMDP 的摄取。
