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Molecular adaptation of a plant-bacterium outer membrane protease towards plague virulence factor Pla

BACKGROUND: Omptins are a family of outer membrane proteases that have spread by horizontal gene transfer in Gram-negative bacteria that infect vertebrates or plants. Despite structural similarity, the molecular functions of omptins differ in a manner that reflects the life style of their host bacte...

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Autores principales: Haiko, Johanna, Laakkonen, Liisa, Westerlund-Wikström, Benita, Korhonen, Timo K
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3048539/
https://www.ncbi.nlm.nih.gov/pubmed/21310089
http://dx.doi.org/10.1186/1471-2148-11-43
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author Haiko, Johanna
Laakkonen, Liisa
Westerlund-Wikström, Benita
Korhonen, Timo K
author_facet Haiko, Johanna
Laakkonen, Liisa
Westerlund-Wikström, Benita
Korhonen, Timo K
author_sort Haiko, Johanna
collection PubMed
description BACKGROUND: Omptins are a family of outer membrane proteases that have spread by horizontal gene transfer in Gram-negative bacteria that infect vertebrates or plants. Despite structural similarity, the molecular functions of omptins differ in a manner that reflects the life style of their host bacteria. To simulate the molecular adaptation of omptins, we applied site-specific mutagenesis to make Epo of the plant pathogenic Erwinia pyrifoliae exhibit virulence-associated functions of its close homolog, the plasminogen activator Pla of Yersinia pestis. We addressed three virulence-associated functions exhibited by Pla, i.e., proteolytic activation of plasminogen, proteolytic degradation of serine protease inhibitors, and invasion into human cells. RESULTS: Pla and Epo expressed in Escherichia coli are both functional endopeptidases and cleave human serine protease inhibitors, but Epo failed to activate plasminogen and to mediate invasion into a human endothelial-like cell line. Swapping of ten amino acid residues at two surface loops of Pla and Epo introduced plasminogen activation capacity in Epo and inactivated the function in Pla. We also compared the structure of Pla and the modeled structure of Epo to analyze the structural variations that could rationalize the different proteolytic activities. Epo-expressing bacteria managed to invade human cells only after all extramembranous residues that differ between Pla and Epo and the first transmembrane β-strand had been changed. CONCLUSIONS: We describe molecular adaptation of a protease from an environmental setting towards a virulence factor detrimental for humans. Our results stress the evolvability of bacterial β-barrel surface structures and the environment as a source of progenitor virulence molecules of human pathogens.
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spelling pubmed-30485392011-03-05 Molecular adaptation of a plant-bacterium outer membrane protease towards plague virulence factor Pla Haiko, Johanna Laakkonen, Liisa Westerlund-Wikström, Benita Korhonen, Timo K BMC Evol Biol Research Article BACKGROUND: Omptins are a family of outer membrane proteases that have spread by horizontal gene transfer in Gram-negative bacteria that infect vertebrates or plants. Despite structural similarity, the molecular functions of omptins differ in a manner that reflects the life style of their host bacteria. To simulate the molecular adaptation of omptins, we applied site-specific mutagenesis to make Epo of the plant pathogenic Erwinia pyrifoliae exhibit virulence-associated functions of its close homolog, the plasminogen activator Pla of Yersinia pestis. We addressed three virulence-associated functions exhibited by Pla, i.e., proteolytic activation of plasminogen, proteolytic degradation of serine protease inhibitors, and invasion into human cells. RESULTS: Pla and Epo expressed in Escherichia coli are both functional endopeptidases and cleave human serine protease inhibitors, but Epo failed to activate plasminogen and to mediate invasion into a human endothelial-like cell line. Swapping of ten amino acid residues at two surface loops of Pla and Epo introduced plasminogen activation capacity in Epo and inactivated the function in Pla. We also compared the structure of Pla and the modeled structure of Epo to analyze the structural variations that could rationalize the different proteolytic activities. Epo-expressing bacteria managed to invade human cells only after all extramembranous residues that differ between Pla and Epo and the first transmembrane β-strand had been changed. CONCLUSIONS: We describe molecular adaptation of a protease from an environmental setting towards a virulence factor detrimental for humans. Our results stress the evolvability of bacterial β-barrel surface structures and the environment as a source of progenitor virulence molecules of human pathogens. BioMed Central 2011-02-11 /pmc/articles/PMC3048539/ /pubmed/21310089 http://dx.doi.org/10.1186/1471-2148-11-43 Text en Copyright ©2011 Haiko et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Haiko, Johanna
Laakkonen, Liisa
Westerlund-Wikström, Benita
Korhonen, Timo K
Molecular adaptation of a plant-bacterium outer membrane protease towards plague virulence factor Pla
title Molecular adaptation of a plant-bacterium outer membrane protease towards plague virulence factor Pla
title_full Molecular adaptation of a plant-bacterium outer membrane protease towards plague virulence factor Pla
title_fullStr Molecular adaptation of a plant-bacterium outer membrane protease towards plague virulence factor Pla
title_full_unstemmed Molecular adaptation of a plant-bacterium outer membrane protease towards plague virulence factor Pla
title_short Molecular adaptation of a plant-bacterium outer membrane protease towards plague virulence factor Pla
title_sort molecular adaptation of a plant-bacterium outer membrane protease towards plague virulence factor pla
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3048539/
https://www.ncbi.nlm.nih.gov/pubmed/21310089
http://dx.doi.org/10.1186/1471-2148-11-43
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