Lipoprotein signal peptidase (LspA) is a type II signal peptidase (SPase II) critical for processing bacterial lipoproteins. In Salmonella Typhimurium, LspA cleaves the signal peptide from prolipoproteins, enabling their maturation and subsequent localization to the outer membrane. This enzyme is essential for bacterial viability, as lipoproteins are integral to membrane integrity, nutrient uptake, and virulence .
Real-time qRT-PCR studies in related pathogens (e.g., R. typhi) demonstrate that lspA transcription peaks during early infection (preinfection and 48 h postinfection) and declines during host cell lysis . Co-expression with lgt (prolipoprotein transferase) and lepB (SPase I) suggests coordinated regulation of lipoprotein and non-lipoprotein secretion pathways .
Although S. Typhimurium lspA itself is not a vaccine target, its role in lipoprotein maturation indirectly impacts vaccine design:
Lipoprotein Knockouts: Deletion of lpp (Braun lipoprotein) in S. Typhimurium attenuates virulence and enhances immune responses to recombinant antigens (e.g., PspA, InvH) .
Adjuvant Effects: Mature lipoproteins activate Toll-like receptor 2 (TLR2), synergizing with LPS (TLR4) to amplify proinflammatory cytokine production .
Lipoprotein Processing: S. Typhimurium requires LspA to process ~14 lipoproteins predicted from genomic analysis, versus 89 secretory proteins processed by SPase I (LepB) .
Antibiotic Sensitivity: Globomycin inhibits LspA, causing accumulation of unprocessed prolipoproteins and bacterial growth arrest .
Recombinant Antigen Delivery: Attenuated Salmonella strains expressing heterologous antigens (e.g., PspA, InvH) leverage Sec or T3SS pathways for antigen secretion, bypassing LspA-dependent lipoprotein processing .
Enzyme Specificity: Low sequence conservation complicates cross-species complementation studies .
Therapeutic Targeting: SPase II inhibitors like globomycin are potential antimicrobials but require optimization for Salmonella-specific delivery .
Vaccine Engineering: Regulated delayed lysis Salmonella strains (e.g., χ11802) enhance antigen release and mucosal immunity without relying on lipoprotein processing .
KEGG: stm:STM0047
STRING: 99287.STM0047