Abstract
Bacterial lipoproteins are well-recognized microorganism-associated molecular patterns, which interact with Toll-like receptor (TLR) 2, an important pattern recognition receptor of the host innate immune system. Lipoproteins are conjugated with two- or three-acyl chains (di- or tri-acyl), which is essential for appropriate anchoring in the cell membrane as well as for the interaction with TLR2. Lipoproteins have mostly been studied in pathogens and have established roles in various biological processes, such as nutrient import, cell wall cross-linking and remodeling, and host-cell interaction. By contrast, information on the role of lipoproteins in the physiology and host interaction of probiotic bacteria is scarce. By deletion of lgt, encoding prolipoprotein diacylglyceryl transferase, responsible for lipidation of lipoprotein precursors, we investigated the roles of the collective group of lipoproteins in the physiology of the probiotic model strain Lactobacillus plantarum WCFS1 using proteomic analysis of secreted proteins. To investigate the consequences of the lgt mutation in host-cell interaction, the capacity of mutant and wild-type bacteria to stimulate TLR2 signaling and inflammatory responses was compared using (reporter-) cell-based models. These experiments exemplified the critical contribution of the acyl chains of lipoproteins in immunomodulation. To the best of our knowledge, this is the first study that investigated collective lipoprotein functions in a model strain for probiotic lactobacilli, and we show that the lipoproteins in L. plantarum WCFS1 are critical drivers of anti-inflammatory host responses toward this strain.
Highlights
Bacterial lipoproteins are proteins that are post-translationally modified by acyl-conjugation, which anchors the protein on the extracellular face of the cytoplasmic membrane
Since many lipoproteins in Gram-negative bacteria are localized at the outer membrane, defects in lipoprotein biosynthesis will cause mislocalization and/or accumulation of the precursors in the periplasmic space, which has been reported to be lethal to the cells (Matsuyama et al, 1995; Robichon et al, 2005)
In Gram-negative bacteria many lipoproteins are targeted to the outer membrane, and the defective biogenesis of these proteins due to Lgt deficiency may lead to protein accumulation and clogging of the periplasm
Summary
Bacterial lipoproteins are proteins that are post-translationally modified by acyl-conjugation, which anchors the protein on the extracellular face of the cytoplasmic membrane. These lipoproteins contain a typical N-terminal signal sequence that ends with the conserved [L/V/I]-[A/S/T]-[G/A]C motif that is designated “lipobox” (Schenk et al, 2009). In Gramnegative bacteria, the third step is essential for the release and transport of lipoproteins from the cytoplasmic membrane to the outer membrane, but the E. coli-type Lnt enzyme appears to be absent in low-GC-content Gram-positive bacteria of the Firmicutes phylum (Robichon et al, 2005; Hutchings et al, 2009). Tri-acylated lipoproteins have been reported for bacteria belonging to this phylum, including Staphylococcus aureus and Streptococcus pneumoniae, suggesting the presence of an unrecognized Gram-positive N-acyltransferase function (Kurokawa et al, 2009; Asanuma et al, 2011; Bartual et al, 2018)
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