Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/12395
Title: The multifunctional LigB adhesin binds homeostatic proteins with potential roles in cutaneous infection by pathogenic Leptospira interrogans.
Authors: Choy, Henry A
Kelley, Melissa M
Croda, Julio Henrique Rosa
Matsunaga, James
Babbitt, Jane T
Ko, Albert Icksang
Picardeau, Mathieu
Haake, David A
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
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/metabolismo
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
Issue Date: 2011
Publisher: Public Library of Science
Citation: CHOY, H. A. et al. The multifunctional LigB adhesin binds homeostatic proteins with potential roles in cutaneous infection by pathogenic Leptospira interrogans. PLoS One, v. 6, n. 2, p. e16879, 2011.
DOI: 10.1371/journal.pone.0016879
ISSN: 1932-6203
Copyright: open access
Appears in Collections:BA - IGM - Artigos de Periódicos

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