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https://www.arca.fiocruz.br/handle/icict/12395
THE MULTIFUNCTIONAL LIGB ADHESIN BINDS HOMEOSTATIC PROTEINS WITH POTENTIAL ROLES IN CUTANEOUS INFECTION BY PATHOGENIC LEPTOSPIRA INTERROGANS.
Fibrinogênio/metabolismo
Fibronectinas/metabolismo
Leptospira interrogans/metabolismo
Leptospirose/metabolismo
Dermatopatias Bacterianas/metabolismo
Adesinas Bacterianas/química
Anticorpos Antibacterianos/imunologia
Aderência Bacteriana
Fibrina/metabolismo
Humanos
Leptospira interrogans/genética
Leptospirose/microbiologia
Ligação Proteica
Estrutura Terciária de Proteína
Dermatopatias Bacterianas/microbiologia
Transformação Bacteriana
Cicatrização
Author
Affilliation
Albert Einstein College of Medicine. Department of Physiology & Biophysics. Bronx, NY, USA / Research Service. Veterans Affairs Greater Los Angeles Healthcare System. Los Angeles, California, USA
Research Service. Veterans Affairs Greater Los Angeles Healthcare System. Los Angeles, California, USA
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Grande Dourados. Faculty of Health Sciences. Dourados, MGS, Brasil
Albert Einstein College of Medicine. Department of Physiology & Biophysics. Bronx, NY, USA / Research Service. Veterans Affairs Greater Los Angeles Healthcare System. Los Angeles, California, USA
Albert Einstein College of Medicine. Department of Physiology & Biophysics. Bronx, NY, USA / Research Service. Veterans Affairs Greater Los Angeles Healthcare System. Los Angeles, California, USA
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Yale University School of Medicine. Department of Epidemiology and Public Health. Division of Epidemiology of Microbial Diseases. New Haven, Connecticut, USA
Institut Pasteur. Unite de Biologie des Spirochetes. Paris, France
Albert Einstein College of Medicine. Department of Physiology & Biophysics. Bronx, NY, USA / Veterans Affairs Greater Los Angeles Healthcare System. Division of Infectious Diseases. Los Angeles, California, USA / University of California Los Angeles. Department of Urology and Department of Molecular Genetics, Microbiology, and Immunology. Los Angeles, California, USA
Research Service. Veterans Affairs Greater Los Angeles Healthcare System. Los Angeles, California, USA
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Grande Dourados. Faculty of Health Sciences. Dourados, MGS, Brasil
Albert Einstein College of Medicine. Department of Physiology & Biophysics. Bronx, NY, USA / Research Service. Veterans Affairs Greater Los Angeles Healthcare System. Los Angeles, California, USA
Albert Einstein College of Medicine. Department of Physiology & Biophysics. Bronx, NY, USA / Research Service. Veterans Affairs Greater Los Angeles Healthcare System. Los Angeles, California, USA
Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Yale University School of Medicine. Department of Epidemiology and Public Health. Division of Epidemiology of Microbial Diseases. New Haven, Connecticut, USA
Institut Pasteur. Unite de Biologie des Spirochetes. Paris, France
Albert Einstein College of Medicine. Department of Physiology & Biophysics. Bronx, NY, USA / Veterans Affairs Greater Los Angeles Healthcare System. Division of Infectious Diseases. Los Angeles, California, USA / University of California Los Angeles. Department of Urology and Department of Molecular Genetics, Microbiology, and Immunology. Los Angeles, California, USA
Abstract
Leptospirosis is a potentially fatal zoonotic disease in humans and animals caused by pathogenic spirochetes, such as
Leptospira interrogans. The mode of transmission is commonly limited to the exposure of mucous membrane or damaged
skin to water contaminated by leptospires shed in the urine of carriers, such as rats. Infection occurs during seasonal
flooding of impoverished tropical urban habitats with large rat populations, but also during recreational activity in open
water, suggesting it is very efficient. LigA and LigB are surface localized proteins in pathogenic Leptospira strains with
properties that could facilitate the infection of damaged skin. Their expression is rapidly induced by the increase in
osmolarity encountered by leptospires upon transition from water to host. In addition, the immunoglobulin-like repeats of
the Lig proteins bind proteins that mediate attachment to host tissue, such as fibronectin, fibrinogen, collagens, laminin,
and elastin, some of which are important in cutaneous wound healing and repair. Hemostasis is critical in a fresh injury,
where fibrinogen from damaged vasculature mediates coagulation. We show that fibrinogen binding by recombinant LigB
inhibits fibrin formation, which could aid leptospiral entry into the circulation, dissemination, and further infection by
impairing healing. LigB also binds fibroblast fibronectin and type III collagen, two proteins prevalent in wound repair, thus
potentially enhancing leptospiral adhesion to skin openings. LigA or LigB expression by transformation of a nonpathogenic
saprophyte, L. biflexa, enhances bacterial adhesion to fibrinogen. Our results suggest that by binding homeostatic proteins
found in cutaneous wounds, LigB could facilitate leptospirosis transmission. Both fibronectin and fibrinogen binding have
been mapped to an overlapping domain in LigB comprising repeats 9–11, with repeat 11 possibly enhancing binding by a
conformational effect. Leptospirosis patient antibodies react with the LigB domain, suggesting applications in diagnosis and
vaccines that are currently limited by the strain-specific leptospiral lipopolysaccharide coats.
DeCS
Adesinas Bacterianas/metabolismoFibrinogênio/metabolismo
Fibronectinas/metabolismo
Leptospira interrogans/metabolismo
Leptospirose/metabolismo
Dermatopatias Bacterianas/metabolismo
Adesinas Bacterianas/química
Anticorpos Antibacterianos/imunologia
Aderência Bacteriana
Fibrina/metabolismo
Humanos
Leptospira interrogans/genética
Leptospirose/microbiologia
Ligação Proteica
Estrutura Terciária de Proteína
Dermatopatias Bacterianas/microbiologia
Transformação Bacteriana
Cicatrização
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