Molecular characterisation of a putative virulence factor LIC10280 from Leptospira interrogans in the budding yeast...

Leptospirosis, a widespread zoonotic disease caused by Leptospira interrogans, poses a major public health challenge, particularly in tropical regions. Despite progress in genomic studies, many putative virulence factors (VFs) remain uncharacterised. This study focuses on LIC10280, a conserved hypothetical protein identified as a potential VF through yeast-based screening. In silico analysis predicted that LIC10280 possesses a cleavable signal peptide and a β-barrel fold in its mature region, features common to secreted bacterial proteins. BlastP analysis showed that LIC10280 is conserved in pathogenic Leptospira but absent in saprophytic species, suggesting a role in pathogenesis. Growth assay in budding yeast, Saccharomyces cerevisiae revealed that only the full-length LIC10280 inhibited yeast growth and reduced cell viability as confirmed in FUN-1 staining. Fluorescence microscopy study revealed that mature part of LIC10280 was involved in localisation to yeast nucleus without vesicular trafficking. A yeast genetic screen showed that deletion of SCH9, a component of the TORC1 signalling pathway, partially suppressed LIC10280-induced toxicity, implicating a possible link to nutrient-sensing or stress-response pathways. Together, these findings provide new insights into the potential function of LIC10280 and highlight the value of yeast as a model system for studying putative virulence factors of L. interrogans.