The leptospiral LipL21 and LipL41 proteins exhibit a broad spectrum of interactions with host cell components

Takahashi, Michiaki; Af, Teixeira; Nascimento, Ana L. T. O.

doi:10.1080/21505594.2021.1993427

Cited by 17 publications

(14 citation statements)

References 80 publications

(75 reference statements)

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“…LipL21 and LipL41, lipoproteins that are among the most expressed in the outer membrane, were also found to bind to GAGs. LipL21 showed a broad binding profile, by interacting with heparin/heparan sulfate and chondroitin sulfate, while LipL41 bound effectively to chondroitin 4 sulfate ( Takahashi et al., 2021 ).…”

Section: Binding Of Leptospira To Ecm and Cadherinsmentioning

confidence: 99%

“…Interactions have been demonstrated to occur mainly via the lysine residues in proteins and plasminogen kringle domains, since the interactions were inhibited by a lysine analog, as observed by in vitro assay ( Domingos et al., 2012 ; Teixeira et al., 2015 ; Fernandes et al., 2016b ; Vieira and Nascimento, 2016 ; Pereira et al., 2017 ; Passalia et al., 2020a ; Passalia et al., 2021 ). Among many proteins already identified as a plasminogen receptor, the major outer membrane lipoproteins LipL32, LipL21 and LipL41 and the transmembrane protein OmpL1 are included ( Fernandes et al., 2012 ; Vieira et al., 2010 ; Takahashi et al., 2021 ). As reported for the bacteria, plasminogen bound to recombinant proteins is converted to active plasmin in the presence of an exogenous activator.…”

Section: Binding Of Leptospira To Plasma Componentsmentioning

confidence: 99%

“…As reported for the bacteria, plasminogen bound to recombinant proteins is converted to active plasmin in the presence of an exogenous activator. Also, proteins such as rLIC11711, rLIC13259, Lsa24.9, rLIC13086 and LipL41 were able to acquire plasminogen from human serum, suggesting the viability of these interactions under physiological conditions and their possible role in leptospiral virulence ( Cavenague et al., 2019 ; Kochi et al., 2019 ; Rossini et al., 2020 ; Passalia et al., 2021 ; Takahashi et al., 2021 ). Leptospiral immunoglobulin-like proteins, known as Lig proteins, have also been identified as plasminogen-binding.…”

Section: Binding Of Leptospira To Plasma Componentsmentioning

confidence: 99%

See 2 more Smart Citations

A Review on Host-Leptospira Interactions: What We Know and Future Expectations

Daroz

Fernandes

Cavenague

et al. 2021

Front. Cell. Infect. Microbiol.

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Leptospirosis is a widespread zoonosis caused by pathogenic Leptospira spp. It is considered a neglected infectious disease of human and veterinary concern. Our group has been investigating proteins annotated as hypothetical, predicted to be located on the leptospiral surface. Because of their location, these proteins may have the ability to interact with various host components, which could allow establishment of the infection. These proteins act as adherence factors by binding to host receptor molecules, such as the extracellular matrix (ECM) components laminin and glycosaminoglycans to help bacterial colonization. Leptospira also interacts with the host fibrinolytic system, which has been demonstrated to be a powerful tool for invasion mechanisms. The interaction with fibrinogen and thrombin has been shown to reduce fibrin clot formation. Additionally, the degradation of coagulation cascade components by secreted proteases or by acquired surface plasmin could also play a role in reducing clot formation, hence facilitating dissemination during infection. Interaction with host complement system regulators also plays a role in helping bacteria to evade the immune system, facilitating invasion. Interaction of Leptospira to cell receptors, such as cadherins, can contribute to investigate molecules that participate in virulence. To achieve a better understanding of the host-pathogen interaction, leptospiral mutagenesis tools have been developed and explored. This work presents several proteins that mediate binding to components of the ECM, plasma, components of the complement system and cells, to gather research achievements that can be helpful in better understanding the mechanisms of leptospiral-host interactions and discuss genetic manipulation for Leptospira spp. aimed at protein function validation.

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Section: Binding Of Leptospira To Ecm and Cadherinsmentioning

confidence: 99%

Section: Binding Of Leptospira To Plasma Componentsmentioning

confidence: 99%

Section: Binding Of Leptospira To Plasma Componentsmentioning

confidence: 99%

See 1 more Smart Citation

A Review on Host-Leptospira Interactions: What We Know and Future Expectations

Daroz

Fernandes

Cavenague

et al. 2021

Front. Cell. Infect. Microbiol.

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“…Furthermore, LipL21 was isolated together with other known Leptospira OMPs by both Triton X-114 extraction and sucrose density gradient membrane fractionation [ 54 ]. The recombinant LipL21 was found to interact with glycosaminoglycans (GAGs), collagen IV, laminin, E-cadherin, and elastin and these interactions of LipL21 to host cell components represented important steps in adhesion, invasion, and evasion of the immune system [ 55 ]. Interestingly, many pathogens can use GAG to help their adhesion and invasion.…”

Section: Leptospira Membrane Structure and The Virulence Fac...mentioning

confidence: 99%

“…Interestingly, many pathogens can use GAG to help their adhesion and invasion. However, LipL21 and OmpL1 are the only two virulence factors to bind GAG in Leptospira [ 55 ]. In addition to being used as an adhesin, LipL21 has also been found to be a potent inhibitor of neutrophil myeloperoxidase [ 56 ].…”

Section: Leptospira Membrane Structure and The Virulence Fac...mentioning

confidence: 99%

Insight into the Structure, Functions, and Dynamics of the Leptospira Outer Membrane Proteins with the Pathogenicity

Hsu

Yang

2022

Membranes

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Leptospirosis is a widespread zoonosis that frequently occurs in tropical and subtropical countries. Leptospira enters the host through wounds or mucous membranes and spreads to the whole body through the blood, causing systemic infection. Kidneys are the preferential site where Leptospira accumulates, especially in the renal interstitium and renal tubule epithelial cells. Clinical symptoms in humans include high fever, jaundice, renal failure, and severe multiple-organ failure (Weil’s syndrome). Surface-exposed antigens are located at the outermost layer of Leptospira and these potential virulence factors are likely involved in primary host-pathogen interactions, adhesion, and/or invasion. Using the knockout/knockdown techniques to the evaluation of pathogenicity in the virulence factor are the most direct and effective methods and many virulence factors are evaluated including lipopolysaccharides (LPS), Leptospira lipoprotein 32 (LipL32), Leptospira ompA domain protein 22 (Loa22), LipL41, LipL71, Leptospira immunoglobulin-like repeat A (LigA), LigB, and LipL21. In this review, we will discuss the structure, functions, and dynamics of these virulence factors and the roles of these virulence factors in Leptospira pathogenicity. In addition, a protein family with special Leucine-rich repeat (LRR) will also be discussed for their vital role in Leptospira pathogenicity. Finally, these surface-exposed antigens are discussed in the application of the diagnosis target for leptospirosis and compared with the serum microscope agglutination test (MAT), the gold standard for leptospirosis.

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A comprehensive in silico analysis of putative outer membrane and secretory hydrolases from the pathogenic Leptospira: Possible implications in pathogenesis

Shankar,

Shiraz,

Kumar

et al. 2024

Biotech and App Biochem

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Outer surface/membrane and virulent secretory proteins are primarily crucial for pathogenesis. Secreted and outer membrane hydrolases of many pathogens play an important role in attenuating the host immune system. Leptospira expresses many such proteins, and few have been characterized to display various roles, including host immune evasion. However, identification, classification, characterization, and elucidation of the possible role of Leptospira’s outer membrane and secretory hydrolases have yet to be explored. In the present study, we used bioinformatics tools to predict exported proteins from the pathogenic Leptospira proteome. Moreover, we focused on secretory and outer membrane putative hydrolases from the exported proteins to generate a deeper understanding. Our analysis yielded four putative outer/secretory hydrolases, LIC_10995, LIC_11183, LIC_11463, and LIC_12988, containing α/β hydrolase fold and displayed similarity with lipase motif. Moreover, their conservation analysis of the predicted hydrolases across the spectrum of different Leptospira species showed high clustering with the pathogenic species. Outer membrane and secretory proteins with lipolytic activity may have a role in pathogenesis. This is the first bioinformatics analysis of secretory and outer membrane α/β hydrolases from leptospiral species. However, experimental studies are indeed required to unravel this possibility.

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The leptospiral LipL21 and LipL41 proteins exhibit a broad spectrum of interactions with host cell components

Cited by 17 publications

References 80 publications

A Review on Host-Leptospira Interactions: What We Know and Future Expectations

A Review on Host-Leptospira Interactions: What We Know and Future Expectations

Insight into the Structure, Functions, and Dynamics of the Leptospira Outer Membrane Proteins with the Pathogenicity

A comprehensive in silico analysis of putative outer membrane and secretory hydrolases from the pathogenic Leptospira: Possible implications in pathogenesis

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