PLASMINOGEN ACTIVATOR OF YERSINIA PESTIS

Plague has been the cause of three pandemics and has led to the death of millions of people. Plague is a typical zoonosis caused by Yersinia pestis that circulates in populations of wild rodents inhabiting natural plague foci on all continents except for Australia. Transmission of plague is provided...

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Autores principales:	V. V. Evseeva, M. E. Platonov, P. Kh. Kopylov, S. V. Dentovskaya, A. P. Anisimov
Formato:	article
Lenguaje:	RU
Publicado:	Sankt-Peterburg : NIIÈM imeni Pastera 2015
Materias:	yersinia pestis plasminogen activator omptin pathogenicity factor pathogenesis plague Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/4f7e785f963242228c4eba1057a799ea
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spelling	oai:doaj.org-article:4f7e785f963242228c4eba1057a799ea2021-11-22T07:09:47ZPLASMINOGEN ACTIVATOR OF YERSINIA PESTIS2220-76192313-739810.15789/2220-7619-2015-1-27-36https://doaj.org/article/4f7e785f963242228c4eba1057a799ea2015-04-01T00:00:00Zhttps://www.iimmun.ru/iimm/article/view/271https://doaj.org/toc/2220-7619https://doaj.org/toc/2313-7398Plague has been the cause of three pandemics and has led to the death of millions of people. Plague is a typical zoonosis caused by Yersinia pestis that circulates in populations of wild rodents inhabiting natural plague foci on all continents except for Australia. Transmission of plague is provided by flea bites. Circulation of Y. pestis in natural plague foci is supported by a numerous of pathogenicity factors. This review explores one of them, plasminogen activator Pla. This protein is one of representatives of omptins, a family of enterobacterial outer membrane proteases that are responsible for colonization of specific organs or even infection generalization as a result of successful overcoming of the host innate immunity. The review reflects the history of its discovery and studying of its genetic control, biosynthesis, isolation and purification, physicochemical properties. Highly purified preparations of plasminogen activator are deficient in enzymatic activities but renaturation in the presence of Y. pestis lipooligosaccharide restores enzymatic properties of Pla. This pathogenicity factor is absent in representatives of the most ancient phylogenetic group of the plague pathogen, bv. caucasica, while the ancestor of other groups of Y. pestis subsp. microtus obtained in result of horizontal transfer Pla isoform with characteristics similar to properties of omptins from the less virulent enterobacteria. After that in the course of microevolution the “classic” isoform of Pla with increased protease activity was selected that is typical of all highly virulent for humans strains of Y. pestis subsp. pestis. The “classic” isoform of Pla Y. pestis is functionally similar to mammalian plasminogen activators transforming plasminogen into plasmin with the help of limited proteolysis. Pla protease activating plasminogen and also degrading the main plasmin inhibitor — α2-antiplasmin and, respectively, determining Y. pestis ability to lyse fibrin clots preventing bacteria dissemination after bites of infected fleas or subcutaneous challenge is believed to be the main Y. pestis factor responsible for generalization of infectious process. Pla-mediated ability of Y. pestis for selective binding with extracellular matrix and basal membranes may promote further hydrolysis of these structures by the host’s plasmin and overcoming tissue barriers by the pathogen. Y. pestis plasminogen activator also hydrolyses C3 complement component, human antimicrobial peptide — cathelicidin LL-37 and such cytokines as tumor necrosis factor α, interferon γ, interleukin 8 and protein 1 of monocyte chemotaxis. The main endogenic TFPI tissue factor pathway inhibitor also highly susceptible to proteolytic action of Pla, and efficiency of TFPI inactivation is much higher than efficacy of plasminogen activation. The review also debates the possibility of using Pla as a molecular target for prophylaxis and treatment of plague.V. V. EvseevaM. E. PlatonovP. Kh. KopylovS. V. DentovskayaA. P. AnisimovSankt-Peterburg : NIIÈM imeni Pasteraarticleyersinia pestisplasminogen activatoromptinpathogenicity factorpathogenesisplagueInfectious and parasitic diseasesRC109-216RUInfekciâ i Immunitet, Vol 5, Iss 1, Pp 27-36 (2015)
institution	DOAJ
collection	DOAJ
language	RU
topic	yersinia pestis plasminogen activator omptin pathogenicity factor pathogenesis plague Infectious and parasitic diseases RC109-216
spellingShingle	yersinia pestis plasminogen activator omptin pathogenicity factor pathogenesis plague Infectious and parasitic diseases RC109-216 V. V. Evseeva M. E. Platonov P. Kh. Kopylov S. V. Dentovskaya A. P. Anisimov PLASMINOGEN ACTIVATOR OF YERSINIA PESTIS
description	Plague has been the cause of three pandemics and has led to the death of millions of people. Plague is a typical zoonosis caused by Yersinia pestis that circulates in populations of wild rodents inhabiting natural plague foci on all continents except for Australia. Transmission of plague is provided by flea bites. Circulation of Y. pestis in natural plague foci is supported by a numerous of pathogenicity factors. This review explores one of them, plasminogen activator Pla. This protein is one of representatives of omptins, a family of enterobacterial outer membrane proteases that are responsible for colonization of specific organs or even infection generalization as a result of successful overcoming of the host innate immunity. The review reflects the history of its discovery and studying of its genetic control, biosynthesis, isolation and purification, physicochemical properties. Highly purified preparations of plasminogen activator are deficient in enzymatic activities but renaturation in the presence of Y. pestis lipooligosaccharide restores enzymatic properties of Pla. This pathogenicity factor is absent in representatives of the most ancient phylogenetic group of the plague pathogen, bv. caucasica, while the ancestor of other groups of Y. pestis subsp. microtus obtained in result of horizontal transfer Pla isoform with characteristics similar to properties of omptins from the less virulent enterobacteria. After that in the course of microevolution the “classic” isoform of Pla with increased protease activity was selected that is typical of all highly virulent for humans strains of Y. pestis subsp. pestis. The “classic” isoform of Pla Y. pestis is functionally similar to mammalian plasminogen activators transforming plasminogen into plasmin with the help of limited proteolysis. Pla protease activating plasminogen and also degrading the main plasmin inhibitor — α2-antiplasmin and, respectively, determining Y. pestis ability to lyse fibrin clots preventing bacteria dissemination after bites of infected fleas or subcutaneous challenge is believed to be the main Y. pestis factor responsible for generalization of infectious process. Pla-mediated ability of Y. pestis for selective binding with extracellular matrix and basal membranes may promote further hydrolysis of these structures by the host’s plasmin and overcoming tissue barriers by the pathogen. Y. pestis plasminogen activator also hydrolyses C3 complement component, human antimicrobial peptide — cathelicidin LL-37 and such cytokines as tumor necrosis factor α, interferon γ, interleukin 8 and protein 1 of monocyte chemotaxis. The main endogenic TFPI tissue factor pathway inhibitor also highly susceptible to proteolytic action of Pla, and efficiency of TFPI inactivation is much higher than efficacy of plasminogen activation. The review also debates the possibility of using Pla as a molecular target for prophylaxis and treatment of plague.
format	article
author	V. V. Evseeva M. E. Platonov P. Kh. Kopylov S. V. Dentovskaya A. P. Anisimov
author_facet	V. V. Evseeva M. E. Platonov P. Kh. Kopylov S. V. Dentovskaya A. P. Anisimov
author_sort	V. V. Evseeva
title	PLASMINOGEN ACTIVATOR OF YERSINIA PESTIS
title_short	PLASMINOGEN ACTIVATOR OF YERSINIA PESTIS
title_full	PLASMINOGEN ACTIVATOR OF YERSINIA PESTIS
title_fullStr	PLASMINOGEN ACTIVATOR OF YERSINIA PESTIS
title_full_unstemmed	PLASMINOGEN ACTIVATOR OF YERSINIA PESTIS
title_sort	plasminogen activator of yersinia pestis
publisher	Sankt-Peterburg : NIIÈM imeni Pastera
publishDate	2015
url	https://doaj.org/article/4f7e785f963242228c4eba1057a799ea
work_keys_str_mv	AT vvevseeva plasminogenactivatorofyersiniapestis AT meplatonov plasminogenactivatorofyersiniapestis AT pkhkopylov plasminogenactivatorofyersiniapestis AT svdentovskaya plasminogenactivatorofyersiniapestis AT apanisimov plasminogenactivatorofyersiniapestis
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PLASMINOGEN ACTIVATOR OF YERSINIA PESTIS

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