Deciphering the proteome of naturally released extracellular vesicles from Leptospira interrogans serovar Pomona in response to temperature and osmotic stresses

The biogenesis and functions of Leptospira's extracellular vesicles (EVs) remain unclear. The study aimed to characterize EVs that were naturally released from intact leptospires during in vitro culture, as well as under conditions mimicking the host environment during infection, including temperature or osmolarity shift. The EVs were found to contain a group of proteins from the outer membrane and various cytoplasmic proteins, suggesting that they originated from the outer membrane and cytoplasm. These proteins were primarily involved in Leptospira's growth, survival, adaptation, and pathogenicity. Interestingly, the study revealed that Leptospira secreted multifunctional proteins through EVs but might maintain several virulence and virulence-associated proteins in their cells in response to temperature and osmotic stresses. Thus, native leptospiral EVs might act as decoys for the host immune system, while the virulence factors crucial for direct interaction with host components might be preserved in whole cells. This knowledge may contribute to understanding the role of EVs in the pathogenicity of Leptospira and the development of vaccines against leptospirosis in the future.

钩端螺旋体（Leptospira）细胞外囊泡（extracellular vesicles, EVs）的生物发生与功能至今尚未明确。本研究旨在对体外培养过程中，以及模拟感染期间宿主环境（包括温度或渗透压改变）下从完整钩端螺旋体自然释放的细胞外囊泡进行表征。研究发现，此类细胞外囊泡携带一组外膜蛋白与多种胞质蛋白，提示其起源于外膜与胞质区域。这些蛋白主要参与钩端螺旋体的生长、存活、适应及致病过程。有趣的是，本研究发现钩端螺旋体可通过细胞外囊泡分泌多功能蛋白，但在应对温度与渗透压胁迫时，会在胞内留存部分毒力蛋白及毒力相关蛋白。据此推测，天然钩端螺旋体细胞外囊泡可作为宿主免疫系统的诱饵，而与宿主组分直接相互作用的关键毒力因子则会留存于完整菌体中。本研究结果有助于未来解析细胞外囊泡在钩端螺旋体致病过程中的作用，并推动钩端螺旋体病（leptospirosis）疫苗的研发。