期刊
出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2108155118
关键词
Listeriolysin S (LLS); bacteriocin; Listeria monocytogenes (Lm); contact-dependent inhibition (CDI); microfluidic microscopy
资金
- Institut Pasteur
- Institut Carnot Pasteur Microbes et Sante (PasteurInnov Grant LLS-Bact)
- Region Ile-de-France (DIM-MALINF)
- Fondation pour la Recherche Medicale [FDT201904008152]
- Spanish Ministry of Science, Innovation and Universities [RYC-2018-024985-I]
- LabEX Integrative Biology of Emerging Infectious Diseases [ANR LBX-62 IBEID]
LLS is a TOMM produced by hypervirulent clones of Listeria monocytogenes, displaying a contact-dependent inhibition mechanism through direct contact with target bacteria. Additionally, interactions between LLS and lipoteichoic acids (LTAs) influence bacterial susceptibility, suggesting a complex mechanism of action for LLS.
Listeriolysin S (LLS) is a thiazole/oxazole-modified microcin (TOMM) produced by hypervirulent clones of Listeria monocytogenes. LLS targets specific gram-positive bacteria and modulates the host intestinal microbiota composition. To characterize the mechanism of LLS transfer to target bacteria and its bactericidal function, we first investigated its subcellular distribution in LLS-producer bacteria. Using subcellular fractionation assays, transmission electron microscopy, and single-molecule superresolution microscopy, we identified that LLS remains associated with the bacterial cell membrane and cytoplasm and is not secreted to the bacterial extracellular space. Only living LLS-producer bacteria (and not purified LLS-positive bacterial membranes) display bactericidal activity. Applying transwell coculture systems and microfluidic-coupled microscopy, we determined that LLS requires direct contact between LLS-producer and -target bacteria in order to display bactericidal activity, and thus behaves as a contact-dependent bacteriocin. Contact-dependent exposure to LLS leads to permeabilization/depolarization of the target bacterial cell membrane and adenosine triphosphate (ATP) release. Additionally, we show that lipoteichoic acids (LTAs) can interact with LLS and that LTA decorations influence bacterial susceptibility to LLS. Overall, our results suggest that LLS is a TOMM that displays a contact-dependent inhibition mechanism.
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