Department of Genetics and Biotechnology, University of Trás-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal; Functional Genomics and Proteomics Unity, University of Trás-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal; Associated Laboratory for Green Chemistry (LAQV-REQUIMTE), Faculty of Science and Technology, University Nova of Lisbon, 2829-546 Caparica, Portugal.
Bioinformatics Unit, Department of Infectious Diseases, National Institute of Health Dr. Ricardo Jorge, 1600-609 Lisbon, Portugal.
J Proteomics. 2022 Sep 30;268:104714. doi: 10.1016/j.jprot.2022.104714. Epub 2022 Sep 1.
One of the most important livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) genetic lineages is the clonal complex (CC) 398, which can cause typical S. aureus-associated infections in people. In this work, whole-genome sequencing, RNA-sequencing, and gel-based comparative proteomics were applied to study the genetic characteristics of three MRSA CC398 isolates recovered from humans (strains C5621 and C9017), and from an animal (strain OR418). Of the three strains, C9017 presented the broadest resistance genotype, including resistance to fluroquinolone, clindamycin, tiamulin, macrolide and aminoglycoside antimicrobial classes. The scn, sak, and chp genes of the immune evasion cluster system were solely detected in OR418. Pangenome analysis showed a total of 288 strain-specific genes, most of which are hypothetical or phage-related proteins. OR418 had the most pronounced genetic differences. RNAIII (δ-hemolysin) gene was clearly the most expressed gene in OR418 and C5621, but it was not detected in C9017. Significant differences in the proteome profiles were found between strains. For example, the immunoglobulin-binding protein Sbi was more abundant in OR418. Considering that Sbi is a multifunctional immune evasion factor in S. aureus, the results point to OR418 strain having high zoonotic potential. Overall, multiomics biomarker signatures can assume an important role to advance precision medicine in the years to come. SIGNIFICANCE: MRSA is one of the most representative drug-resistant pathogens and its dissemination is increasing due to MRSA capability of establishing new reservoirs. LA-MRSA is considered an emerging problem worldwide and CC398 is one of the most important genetic lineages. In this study, three MRSA CC398 isolates recovered from humans and from a wild animal were analyzed through whole-genome sequencing, RNA-sequencing, and gel-based comparative proteomics in order to gather systems-wide omics data and better understand the genetic characteristics of this lineage to identify distinctive markers and genomic features of relevance to public health.
一种最重要的与家畜相关的耐甲氧西林金黄色葡萄球菌（LA-MRSA）遗传谱系是克隆复合体（CC）398，它可导致人类中典型的金黄色葡萄球菌相关感染。在这项工作中，应用全基因组测序、RNA 测序和基于凝胶的比较蛋白质组学来研究从人类（菌株 C5621 和 C9017）和动物（菌株 OR418）中回收的三个 MRSA CC398 分离株的遗传特征。在这三个菌株中，C9017 表现出最广泛的耐药基因型，包括对氟喹诺酮类、克林霉素、替米考星、大环内酯类和氨基糖苷类抗菌药物的耐药性。免疫逃逸簇系统的 scn、sak 和 chp 基因仅在 OR418 中检测到。泛基因组分析显示共有 288 个菌株特异性基因，其中大多数为假设或噬菌体相关蛋白。OR418 具有最明显的遗传差异。RNAIII（δ-溶血素）基因在 OR418 和 C5621 中显然是表达最丰富的基因，但在 C9017 中未检测到。菌株间的蛋白质组谱存在显著差异。例如，免疫球蛋白结合蛋白 Sbi 在 OR418 中更为丰富。考虑到 Sbi 是金黄色葡萄球菌中一种多功能的免疫逃逸因子，结果表明 OR418 菌株具有较高的人畜共患病潜力。总体而言，多组学生物标志物特征可以在未来几年为精准医学的发展发挥重要作用。意义：耐甲氧西林金黄色葡萄球菌（MRSA）是最具代表性的耐药病原体之一，由于 MRSA 有能力建立新的储存库，其传播正在增加。LA-MRSA 被认为是全世界的一个新兴问题，CC398 是最重要的遗传谱系之一。在这项研究中，通过全基因组测序、RNA 测序和基于凝胶的比较蛋白质组学，分析了从人类和野生动物中回收的三个 MRSA CC398 分离株，以收集系统范围的组学数据，更好地了解该谱系的遗传特征，确定与公共卫生相关的独特标记和基因组特征。
