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

DOI: 10.1186/1471-2148-11-43

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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.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.Analyses of genomic sequences of bacterial pathogens have given an unprecedented view into their biology and evolutionary processes [1,2]. A conclusion from these studies is that highly similar genes, many of which are associated with bacterial virulence, are found across great phylogenetic distances and in different genetic elements, which is indicative of horizontal gene transfer. These families of virulence factors - including toxins, transport systems, adhesins, and antibiotic resistance factors - have evolved by adaptive radiation of a functional progenitor molecule to and within other strains and species to support survival in differing ecological niches [2]. The adaptation, or "evolutionary fine-tuning" of virulence factors that results in increased fitness, can involve modification of catalytic efficiency or substrate specificity of an enzyme, or alteration of bacterial interactions with target cells [2]. The mechanisms of horizontal gene transfer and th


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