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.