Characterization of a novel protein of Leptospira interrogans exhibiting plasminogen, vitronectin and complement binding properties

Cavenague, Maria F.; Teixeira, Aline F.; Filho, Alaor Santos; Souza, Gisele Oliveira de; Vasconcellos, Sílvio Arruda; Heinemann, Marcos Bryan; Nascimento, Ana L. T. O.

doi:10.1016/j.ijmm.2018.12.005

Cited by 17 publications

(27 citation statements)

References 87 publications

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“…The deleterious excessive complement activation must be controlled by different cell surface and soluble regulators ( Kim & Song, 2006 ). It has been demonstrated that pathogenic leptospires have several surface proteins able to bind soluble complement regulatory proteins and terminal complement protein as a mechanism of immune evasion ( Meri et al., 2005 ; Siqueira et al., 2017 ; Cavenague et al., 2019 ). Likewise, rLIC13086 exhibited dose-dependent interactions with C4b, C5b6, C7, C8, and C9 molecules of the complement cascade and these bindings may affect the complete MAC formation in the surface of the bacteria.…”

Section: Discussionmentioning

confidence: 99%

“…The initial process of infection consists of leptospires’ adhesion onto extracellular matrix molecules in the host epithelial skin tissue. This step is mediated by leptospiral outer membrane adhesins, of which several were already characterized ( Vieira et al., 2014 ; Figueredo et al., 2017 ; Pereira et al., 2017 ; Cavenague et al., 2019 ; Kochi et al., 2019 ; Rossini et al., 2019 ; Passalia et al., 2020a ). When leptospires reach the bloodstream, they are able to interact with circulating host plasma components ( Vieira et al., 2020 ).…”

Section: Introductionmentioning

confidence: 99%

“…Surface exposed protein in leptospires can interact with human fibrinogen leading to a partial inhibition of fibrin clot formation thus facilitating the dissemination ( Oliveira et al., 2013 ; Fernandes et al., 2015 ). Furthermore, several leptospiral surface proteins interact with regulators and components of the host complement system as a mechanism of innate immune evasion ( Siqueira et al., 2017 ; Cavenague et al., 2019 ; Kochi et al., 2019 ; Passalia et al., 2020a ).…”

Section: Introductionmentioning

confidence: 99%

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A Novel Leptospira interrogans Protein LIC13086 Inhibits Fibrin Clot Formation and Interacts With Host Components

Passalia

Heinemann

Vieira

et al. 2021

Front. Cell. Infect. Microbiol.

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Leptospirosis is a neglected zoonosis, caused by pathogenic spirochetes bacteria of the genus Leptospira. The molecular mechanisms of leptospirosis infection are complex, and it is becoming clear that leptospires express several functionally redundant proteins to invade, disseminate, and escape the host’s immune response. Here, we describe a novel leptospiral protein encoded by the gene LIC13086 as an outer membrane protein. The recombinant protein LIC13086 can interact with the extracellular matrix component laminin and bind plasminogen, thus possibly participating during the adhesion process and dissemination. Also, by interacting with fibrinogen and plasma fibronectin, the protein LIC13086 probably has an inhibitory effect in the fibrin clot formation during the infection process. The newly characterized protein can also bind molecules of the complement system and the regulator C4BP and, thus, might have a role in the evasion mechanism of Leptospira. Taken together, our results suggest that the protein LIC13086 may have a multifunctional role in leptospiral pathogenesis, participating in host invasion, dissemination, and immune evasion processes.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Novel Leptospira interrogans Protein LIC13086 Inhibits Fibrin Clot Formation and Interacts With Host Components

Passalia

Heinemann

Vieira

et al. 2021

Front. Cell. Infect. Microbiol.

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“…Several microorganisms, including pathogenic Leptospira species, are known to be able to bind Plg and induce the secretion of activators by endothelial cells, thereby generating surface-bound PLA as a form of tissue penetration and immune system evasion [ 35 ]. Several leptospiral OMPs have been characterized as being capable of binding to Plg/Pla, including rLIC11711 [ 25 , 36 , 37 , 38 , 39 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

“…The low affinity of LIC11711 for complement system components and regulators [ 25 ] is most likely the reason for serum vulnerability of recombinant L. biflexa . As reported in the literature, other OMPs are potentially involved in the serum resistance of pathogenic leptospires by binding complement components and regulators [ 36 , 45 , 47 ].…”

Section: Discussionmentioning

confidence: 99%

Heterologous Expression of the Pathogen-Specific LIC11711 Gene in the Saprophyte L. biflexa Increases Bacterial Binding to Laminin and Plasminogen

2020

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Leptospirosis is a febrile disease and the etiological agents are pathogenic bacteria of the genus Leptospira. The leptospiral virulence mechanisms are not fully understood and the application of genetic tools is still limited, despite advances in molecular biology techniques. The leptospiral recombinant protein LIC11711 has shown interaction with several host components, indicating a potential function in virulence. This study describes a system for heterologous expression of the L. interrogans gene lic11711 using the saprophyte L. biflexa serovar Patoc as a surrogate, aiming to investigate its possible activity in bacterial virulence. Heterologous expression of LIC11711 was performed using the pMaOri vector under regulation of the lipL32 promoter. The protein was found mainly on the leptospiral outer surface, confirming its location. The lipL32 promoter enhanced the expression of LIC11711 in L. biflexa compared to the pathogenic strain, indicating that this strategy may be used to overexpress low-copy proteins. The presence of LIC11711 enhanced the capacity of L. biflexa to adhere to laminin (Lam) and plasminogen (Plg)/plasmin (Pla) in vitro, suggesting the involvement of this protein in bacterial pathogenesis. We show for the first time that the expression of LIC11711 protein of L. interrogans confers a virulence-associated phenotype on L. biflexa, pointing out possible mechanisms used by pathogenic leptospires.

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Strategies used by Leptospira spirochetes to evade the host complement system

Barbosa

Isaac

2020

FEBS Letters

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Leptospires are highly invasive spirochetes equipped with efficient strategies for dissemination in the host. The Leptospira genus currently comprises 64 species divided into two major clades: the saprophytes composed of nonpathogenic, free-living organisms, and the pathogens encompassing all the species that cause mild or severe infections in humans and animals. While saprophytes are highly susceptible to the lytic action of the complement system, pathogenic (virulent) strains have evolved virulence strategies that allow efficient colonization of a variety of hosts and target organs, including mechanisms to circumvent hosts' innate and acquired immune responses. Pathogenic Leptospira avoid complement-mediated killing by recruiting host complement regulatory proteins and by targeting complement proteins using own and host-expressed proteases. This review outlines the role of complement in eradicating saprophytic Leptospira and the stratagems adopted by pathogenic Leptospira to maneuver the host complement system for their benefit.

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Characterization of a novel protein of Leptospira interrogans exhibiting plasminogen, vitronectin and complement binding properties

Cited by 17 publications

References 87 publications

A Novel Leptospira interrogans Protein LIC13086 Inhibits Fibrin Clot Formation and Interacts With Host Components

A Novel Leptospira interrogans Protein LIC13086 Inhibits Fibrin Clot Formation and Interacts With Host Components

Heterologous Expression of the Pathogen-Specific LIC11711 Gene in the Saprophyte L. biflexa Increases Bacterial Binding to Laminin and Plasminogen

Strategies used by Leptospira spirochetes to evade the host complement system

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