The Role of Properdin in Killing of Non-Pathogenic Leptospira biflexa
Properdin (P) is a positive regulatory protein that stabilizes the C3 convertase and C5 convertase of the complement alternative pathway (AP). Several studies have suggested that properdin can bind directly to the surface of certain pathogens regardless of the presence of C3bBb. Saprophytic Leptospi...
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| Format: | Article |
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Frontiers Media S.A.
2020-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2020.572562/full |
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| author | Adriana Patricia Granados Martinez Patrícia Antonia Estima Abreu Silvio de Arruda Vasconcellos Paulo Lee Ho Viviana P. Ferreira Gurpanna Saggu Angela Silva Barbosa Lourdes Isaac |
| author_facet | Adriana Patricia Granados Martinez Patrícia Antonia Estima Abreu Silvio de Arruda Vasconcellos Paulo Lee Ho Viviana P. Ferreira Gurpanna Saggu Angela Silva Barbosa Lourdes Isaac |
| author_sort | Adriana Patricia Granados Martinez |
| collection | DOAJ |
| description | Properdin (P) is a positive regulatory protein that stabilizes the C3 convertase and C5 convertase of the complement alternative pathway (AP). Several studies have suggested that properdin can bind directly to the surface of certain pathogens regardless of the presence of C3bBb. Saprophytic Leptospira are susceptible to complement-mediated killing, but the interaction of properdin with Leptospira spp. has not been evaluated so far. In this work, we demonstrate that properdin present in normal human serum, purified properdin, as well as properdin oligomers P2, P3, and P4, interact with Leptospira. Properdin can bind directly to the bacterial surface even in the absence of C3b. In line with our previous findings, AP activation was shown to be important for killing non-pathogenic L. biflexa, and properdin plays a key role in this process since this microorganism survives in P-depleted human serum and the addition of purified properdin to P-depleted human serum decreases the number of viable leptospires. A panel of pathogenic L.interrogans recombinant proteins was used to identify putative properdin targets. Lsa30, an outer membrane protein from L. interrogans, binds to unfractionated properdin and to a lesser extent to P2-P4 properdin oligomers. In conclusion, properdin plays an important role in limiting bacterial proliferation of non-pathogenic Leptospira species. Once bound to the leptospiral surface, this positive complement regulatory protein of the AP contributes to the formation of the C3 convertase on the leptospire surface even in the absence of prior addition of C3b. |
| first_indexed | 2024-12-22T20:07:52Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-22T20:07:52Z |
| publishDate | 2020-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-fcda22c2f66e42f5b048706ac202455a2022-12-21T18:14:06ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-11-011110.3389/fimmu.2020.572562572562The Role of Properdin in Killing of Non-Pathogenic Leptospira biflexaAdriana Patricia Granados Martinez0Patrícia Antonia Estima Abreu1Silvio de Arruda Vasconcellos2Paulo Lee Ho3Viviana P. Ferreira4Gurpanna Saggu5Angela Silva Barbosa6Lourdes Isaac7Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, BrazilLaboratory of Bacteriology, Butantan Institute, São Paulo, BrazilLaboratory of Bacterial Zoonoses, Faculty of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, BrazilLaboratory of Bacteriology, Butantan Institute, São Paulo, BrazilDepartment of Medical Microbiology and Immunology, College of Medicine and Life Sciences, University of Toledo, Toledo, OH, United StatesDepartment of Medical Microbiology and Immunology, College of Medicine and Life Sciences, University of Toledo, Toledo, OH, United StatesLaboratory of Bacteriology, Butantan Institute, São Paulo, BrazilDepartment of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, BrazilProperdin (P) is a positive regulatory protein that stabilizes the C3 convertase and C5 convertase of the complement alternative pathway (AP). Several studies have suggested that properdin can bind directly to the surface of certain pathogens regardless of the presence of C3bBb. Saprophytic Leptospira are susceptible to complement-mediated killing, but the interaction of properdin with Leptospira spp. has not been evaluated so far. In this work, we demonstrate that properdin present in normal human serum, purified properdin, as well as properdin oligomers P2, P3, and P4, interact with Leptospira. Properdin can bind directly to the bacterial surface even in the absence of C3b. In line with our previous findings, AP activation was shown to be important for killing non-pathogenic L. biflexa, and properdin plays a key role in this process since this microorganism survives in P-depleted human serum and the addition of purified properdin to P-depleted human serum decreases the number of viable leptospires. A panel of pathogenic L.interrogans recombinant proteins was used to identify putative properdin targets. Lsa30, an outer membrane protein from L. interrogans, binds to unfractionated properdin and to a lesser extent to P2-P4 properdin oligomers. In conclusion, properdin plays an important role in limiting bacterial proliferation of non-pathogenic Leptospira species. Once bound to the leptospiral surface, this positive complement regulatory protein of the AP contributes to the formation of the C3 convertase on the leptospire surface even in the absence of prior addition of C3b.https://www.frontiersin.org/articles/10.3389/fimmu.2020.572562/fullproperdinLeptospiracomplement systemalternative pathwaybacteria killing ability |
| spellingShingle | Adriana Patricia Granados Martinez Patrícia Antonia Estima Abreu Silvio de Arruda Vasconcellos Paulo Lee Ho Viviana P. Ferreira Gurpanna Saggu Angela Silva Barbosa Lourdes Isaac The Role of Properdin in Killing of Non-Pathogenic Leptospira biflexa Frontiers in Immunology properdin Leptospira complement system alternative pathway bacteria killing ability |
| title | The Role of Properdin in Killing of Non-Pathogenic Leptospira biflexa |
| title_full | The Role of Properdin in Killing of Non-Pathogenic Leptospira biflexa |
| title_fullStr | The Role of Properdin in Killing of Non-Pathogenic Leptospira biflexa |
| title_full_unstemmed | The Role of Properdin in Killing of Non-Pathogenic Leptospira biflexa |
| title_short | The Role of Properdin in Killing of Non-Pathogenic Leptospira biflexa |
| title_sort | role of properdin in killing of non pathogenic leptospira biflexa |
| topic | properdin Leptospira complement system alternative pathway bacteria killing ability |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2020.572562/full |
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