Exoproteome Profiling Reveals Increased Secretion of Adhesins and Proteases by Leptospira interrogans to Facilitate Host Colonization and Immune Modulation

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 Leptospira interrogans expressed under pathogenic conditions possesses a rational diagnostic significance due to its consistent presence in body fluids. L. interrogans 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 Leptospira 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.