Department of Respiratory Medicine, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
School of Basic Medicine, Guangxi Medical University, Nanning, Guangxi, China.
Fungal Genet Biol. 2019 Sep;130:54-61. doi: 10.1016/j.fgb.2019.05.002. Epub 2019 May 7.
Talaromyces marneffei (T. marneffei) is a medically important opportunistic dimorphic fungus that infects both humans and bamboo rats. However, the mechanisms of transmission and pathogenicity of T. marneffei are poorly understood. In our study, we combined Illumina and PacBio sequencing technologies to sequence and assemble a complete genome of T. marneffei. To elucidate the transmission route and source, we sequenced three additional T. marneffei isolates using Illumina sequencing technology. Variations among isolates were used to develop a multilocus sequence typing (MLST) system comprising five housekeeping genes that can be used to discriminate between isolates derived from different sources. Our analysis revealed that human and bamboo rat share identical genotypes in these five loci. Thus, we hypothesized that T. marneffei is transmitted to humans through inhalation of spores in the surrounding environment into the lungs and that the bamboo rat can serve as an important natural reservoir for pathogens. Furthermore, we also identified temperature-dependent polyketide synthases, non-ribosomal peptide synthetases and secreted proteins as putative pathogenicity-related factors. In addition, we identified antifungal drug targets that can be investigated in future studies to elucidate the mechanisms underlying drug resistance. In summary, our study presents the basic features of the T. marneffei genome and provides insights into the transmission and pathogenicity of T. marneffei, which warrant fundamental experimental research.
马尔尼菲青霉（Talaromyces marneffei，T. marneffei）是一种重要的医学机会性双相真菌，可感染人类和竹鼠。然而，马尔尼菲青霉的传播和致病机制尚不清楚。在我们的研究中，我们结合了 Illumina 和 PacBio 测序技术，对 T. marneffei 进行了全基因组测序和组装。为了阐明其传播途径和来源，我们使用 Illumina 测序技术对另外三个 T. marneffei 分离株进行了测序。通过对分离株之间的变异进行分析，我们开发了一种包含五个管家基因的多位点序列分型（MLST）系统，可以用来区分来自不同来源的分离株。我们的分析表明，人类和竹鼠在这五个基因座上具有相同的基因型。因此，我们假设 T. marneffei 通过吸入周围环境中的孢子进入肺部而传播给人类，并且竹鼠可以作为病原体的重要天然储主。此外，我们还鉴定了温度依赖性聚酮合酶、非核糖体肽合成酶和分泌蛋白作为潜在的致病性相关因子。此外，我们还鉴定了抗真菌药物靶点，可在未来的研究中进行调查，以阐明耐药机制。总之，本研究介绍了 T. marneffei 基因组的基本特征，并深入了解了 T. marneffei 的传播和致病性，值得进行基础性实验研究。
