ArticlePLoS pathogens2017
LipL21 lipoprotein binding to peptidoglycan enables Leptospira interrogans to escape NOD1 and NOD2 recognition.
Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 55 citations in OpenAlex.
- β-Lactam antibiotics trigger mouse TLR2/4- and human TLR2/5-dependent Jarisch-Herxheimer reaction in leptospirosis.bioRxiv : the preprint server for biology · 2026Article
- A periplasmic layer formed by an outer membrane lipoprotein governs the cell-envelope integrity and stiffness of Leptospira interrogans.Communications biology · 2026Article
- Leptospira and Leptospirosis: A Review of Species Classifications, Genomes, Morphological Structures, Antimicrobial Resistances, Transmissions, and Clinical Manifestations.Current microbiology · 2026Review
- Peptidoglycan architecture dictates protein interactions, tissue tropism, and arthritis in the Lyme disease spirochete Borrelia burgdorferi.PLoS pathogens · 2026Article
- Single-cell transcriptomics uncovers key immune drivers of vaccine efficacy in cattle.BMC genomics · 2025Article
- Myocarditis and neutrophil-mediated vascular leakage but not cytokine storm associated with fatal murine leptospirosis.EBioMedicine · 2025Article
- Cellular Pathophysiology of Leptospirosis: Role of Na/K-ATPase.Microorganisms · 2023Review
- Evaluation ofFrontiers in microbiology · 2023Article
- Insight into the Structure, Functions, and Dynamics of theMembranes · 2022Review
- Alive Pathogenic and Saprophytic Leptospires Enter and Exit Human and Mouse Macrophages With No Intracellular Replication.Frontiers in cellular and infection microbiology · 2022Article
- Host and Species-Specificities of Pattern Recognition Receptors Upon Infection WithFrontiers in cellular and infection microbiology · 2022Review
- Screening of Surface-Exposed Lipoproteins ofFrontiers in microbiology · 2022Article
- Pathogenic Leptospires Limit Dendritic Cell Activation Through Avoidance of TLR4 and TRIF Signaling.Frontiers in immunology · 2022Article
- Bacterial subversion of NLR-mediated immune responses.Frontiers in immunology · 2022Review
- The leptospiral LipL21 and LipL41 proteins exhibit a broad spectrum of interactions with host cell components.Virulence · 2021Article
- Pathogenesis insights from an ancient and ubiquitous spirochete.PLoS pathogens · 2021Review
- Bovine endometrial cells do not mount an inflammatory response toReproduction & fertility · 2021Article
- The peptidoglycan-associated protein NapA plays an important role in the envelope integrity and in the pathogenesis of the lyme disease spirochete.PLoS pathogens · 2021Article
- Borrelia peptidoglycan interacting Protein (BpiP) contributes to the fitness of Borrelia burgdorferi against host-derived factors and influences virulence in mouse models of Lyme disease.PLoS pathogens · 2021Article
- Anti-Leptospira immunoglobulin profiling in mice reveals strain specific IgG and persistent IgM responses associated with virulence and renal colonization.PLoS neglected tropical diseases · 2021Article
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Leptospirosis is a widespread zoonosis, potentially severe in humans, caused by spirochetal bacteria, Leptospira interrogans (L. interrogans). Host defense mechanisms involved in leptospirosis are poorly understood. Recognition of lipopolysaccharide (LPS) and lipoproteins by Toll-Like Receptors (TLR)4 and TLR2 is crucial for clearance of leptospires in mice, yet the role of Nucleotide Oligomerization Domain (NOD)-like receptors (NOD)1 and NOD2, recognizing peptidoglycan (PG) fragments has not previously been examined. Here, we show that pathogenic leptospires escape from NOD1 and NOD2 recognition both in vitro and in vivo, in mice. We found that leptospiral PG is resistant to digestion by certain hydrolases and that a conserved outer membrane lipoprotein of unknown function, LipL21, specific for pathogenic leptospires, is tightly bound to the PG. Leptospiral PG prepared from a mutant not expressing LipL21 (lipl21-) was more readily digested than the parental or complemented strains. Muropeptides released from the PG of the lipl21- mutant, or prepared using a procedure to eliminate the LipL21 protein from the PG of the parental strain, were recognized in vitro by the human NOD1 (hNOD1) and NOD2 (hNOD2) receptors, suggesting that LipL21 protects PG from degradation into muropeptides. LipL21 expressed in E. coli also resulted in impaired PG digestion and NOD signaling. We found that murine NOD1 (mNOD1) did not recognize PG of L. interrogans. This result was confirmed by mass spectrometry showing that leptospiral PG was primarily composed of MurTriDAP, the natural agonist of hNOD1, and contained only trace amounts of the tetra muropeptide, the mNOD1 agonist. Finally, in transgenic mice expressing human NOD1 and deficient for the murine NOD1, we showed enhanced clearance of a lipl21- mutant compared to the complemented strain, or to what was observed in NOD1KO mice, suggesting that LipL21 facilitates escape from immune surveillance in humans. These novel mechanisms allowing L. interrogans to escape recognition by the NOD receptors may be important in circumventing innate host responses.
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