Sarma Abhijit, Phukan Homen, Devasahayam Arokia Balaya Rex, Thoduvayil Sikha, Dhandapani Gunasekaran, Christie Swamidurai Arul Diana, Prasad Thottethodi Subrahmanya Keshava, Madanan Madathiparambil Gopalakrishnan
ICMR - Regional Medical Research Centre, Port Blair 744103, Andaman and Nicobar Islands, India.
Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore 575018, India.
ACS Omega. 2025 Jul 27;10(30):32728-32743. doi: 10.1021/acsomega.4c10983. eCollection 2025 Aug 5.
Leptospirosis, a re-emerging zoonotic disease, is challenging human and animal health due to the lack of early and rapid diagnostic tools and effective vaccines. The exoproteome of the pathogen expressed under pathogenic conditions possesses a rational diagnostic significance due to its consistent presence in body fluids. were challenged to conditions simulating infection using physiological temperatures and osmolarity. Using state-of-the-art extraction techniques, efficient enrichment of nonabundant proteins, and high-resolution LC-MS/MS, we identified 1575 exoproteins from both the pathogen surface and culture supernatant. The results indicate a significant upregulation of 155 exoproteins, of which 41 were predicted to have moonlighting properties, 35 were identified as adhesins, and several proteins were components of the type 2 secretion system (T2SS). Additionally, 10 proteins showed extracellular matrix (ECM) binding properties, out of which 4 orthologs were found using the T2SS. The overall characteristics of upregulated proteins show that they can help establish infection, invasion, and protection from the host defense, thereby providing new insights into the pathogen to confront the host via an increased energy level, secretion system, and host ECM binding molecules. Furthermore, the study suggests potential candidates for efficient antileptospiral countermeasures.
钩端螺旋体病是一种再度出现的人畜共患病，由于缺乏早期快速诊断工具和有效的疫苗，对人类和动物健康构成了挑战。病原体在致病条件下表达的外蛋白质组由于在体液中持续存在而具有合理的诊断意义。我们将其置于模拟感染的条件下，采用生理温度和渗透压进行挑战。利用最先进的提取技术、对非丰富蛋白质的高效富集以及高分辨率液相色谱-串联质谱技术，我们从病原体表面和培养上清液中鉴定出了1575种外蛋白质。结果表明有155种外蛋白质显著上调，其中41种被预测具有兼职功能，35种被鉴定为黏附素，还有几种蛋白质是2型分泌系统（T2SS）的组成成分。此外，有10种蛋白质表现出细胞外基质（ECM）结合特性，其中4种直系同源物是通过T2SS发现的。上调蛋白质的总体特征表明，它们有助于建立感染、侵袭以及抵御宿主防御，从而通过提高能量水平、分泌系统和宿主ECM结合分子为病原体对抗宿主提供新的见解。此外，该研究还提出了高效抗钩端螺旋体对策的潜在候选物。
