Serum-Mediated Cleavage of <italic toggle="yes">Bacillus anthracis</italic> Protective Antigen Is a Two-Step Process That Involves a Serum Carboxypeptidase

ABSTRACT Much of our understanding of the activity of anthrax toxin is based on in vitro systems, which delineate the interaction between Bacillus anthracis toxins and the cell surface. However, these systems fail to account for the intimate association of B. anthracis with the circulatory system, i...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	David L. Goldman, Edward Nieves, Antonio Nakouzi, Johanna Rivera, Ei Ei Phyu, Than Htut Win, Jacqueline M. Achkar, Arturo Casadevall
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	anthrax proteases toxin Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/2c05a029c5454184bf972a4420b5cd48
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:2c05a029c5454184bf972a4420b5cd48
record_format	dspace
spelling	oai:doaj.org-article:2c05a029c5454184bf972a4420b5cd482021-11-15T15:24:22ZSerum-Mediated Cleavage of <italic toggle="yes">Bacillus anthracis</italic> Protective Antigen Is a Two-Step Process That Involves a Serum Carboxypeptidase10.1128/mSphere.00091-182379-5042https://doaj.org/article/2c05a029c5454184bf972a4420b5cd482018-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00091-18https://doaj.org/toc/2379-5042ABSTRACT Much of our understanding of the activity of anthrax toxin is based on in vitro systems, which delineate the interaction between Bacillus anthracis toxins and the cell surface. However, these systems fail to account for the intimate association of B. anthracis with the circulatory system, including the contribution of serum proteins to the host response and processing of anthrax toxins. Using a variety of immunological techniques to inhibit serum processing of B. anthracis protective antigen (PA) along with mass spectrometry analysis, we demonstrate that serum digests PA via 2 distinct reactions. In the first reaction, serum cleaves PA83 into 2 fragments to produce PA63 and PA20 fragments, similarly to that observed following furin digestion. This is followed by carboxypeptidase-mediated removal of the carboxy-terminal arginine and lysines from PA20. IMPORTANCE Our findings identify a serum-mediated modification of PA20 that has not been previously described. These observations further imply that the processing of PA is more complex than currently thought. Additional study is needed to define the contribution of serum processing of PA to the host response and individual susceptibility to anthrax.David L. GoldmanEdward NievesAntonio NakouziJohanna RiveraEi Ei PhyuThan Htut WinJacqueline M. AchkarArturo CasadevallAmerican Society for MicrobiologyarticleanthraxproteasestoxinMicrobiologyQR1-502ENmSphere, Vol 3, Iss 3 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	anthrax proteases toxin Microbiology QR1-502
spellingShingle	anthrax proteases toxin Microbiology QR1-502 David L. Goldman Edward Nieves Antonio Nakouzi Johanna Rivera Ei Ei Phyu Than Htut Win Jacqueline M. Achkar Arturo Casadevall Serum-Mediated Cleavage of <italic toggle="yes">Bacillus anthracis</italic> Protective Antigen Is a Two-Step Process That Involves a Serum Carboxypeptidase
description	ABSTRACT Much of our understanding of the activity of anthrax toxin is based on in vitro systems, which delineate the interaction between Bacillus anthracis toxins and the cell surface. However, these systems fail to account for the intimate association of B. anthracis with the circulatory system, including the contribution of serum proteins to the host response and processing of anthrax toxins. Using a variety of immunological techniques to inhibit serum processing of B. anthracis protective antigen (PA) along with mass spectrometry analysis, we demonstrate that serum digests PA via 2 distinct reactions. In the first reaction, serum cleaves PA83 into 2 fragments to produce PA63 and PA20 fragments, similarly to that observed following furin digestion. This is followed by carboxypeptidase-mediated removal of the carboxy-terminal arginine and lysines from PA20. IMPORTANCE Our findings identify a serum-mediated modification of PA20 that has not been previously described. These observations further imply that the processing of PA is more complex than currently thought. Additional study is needed to define the contribution of serum processing of PA to the host response and individual susceptibility to anthrax.
format	article
author	David L. Goldman Edward Nieves Antonio Nakouzi Johanna Rivera Ei Ei Phyu Than Htut Win Jacqueline M. Achkar Arturo Casadevall
author_facet	David L. Goldman Edward Nieves Antonio Nakouzi Johanna Rivera Ei Ei Phyu Than Htut Win Jacqueline M. Achkar Arturo Casadevall
author_sort	David L. Goldman
title	Serum-Mediated Cleavage of <italic toggle="yes">Bacillus anthracis</italic> Protective Antigen Is a Two-Step Process That Involves a Serum Carboxypeptidase
title_short	Serum-Mediated Cleavage of <italic toggle="yes">Bacillus anthracis</italic> Protective Antigen Is a Two-Step Process That Involves a Serum Carboxypeptidase
title_full	Serum-Mediated Cleavage of <italic toggle="yes">Bacillus anthracis</italic> Protective Antigen Is a Two-Step Process That Involves a Serum Carboxypeptidase
title_fullStr	Serum-Mediated Cleavage of <italic toggle="yes">Bacillus anthracis</italic> Protective Antigen Is a Two-Step Process That Involves a Serum Carboxypeptidase
title_full_unstemmed	Serum-Mediated Cleavage of <italic toggle="yes">Bacillus anthracis</italic> Protective Antigen Is a Two-Step Process That Involves a Serum Carboxypeptidase
title_sort	serum-mediated cleavage of <italic toggle="yes">bacillus anthracis</italic> protective antigen is a two-step process that involves a serum carboxypeptidase
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/2c05a029c5454184bf972a4420b5cd48
work_keys_str_mv	AT davidlgoldman serummediatedcleavageofitalictoggleyesbacillusanthracisitalicprotectiveantigenisatwostepprocessthatinvolvesaserumcarboxypeptidase AT edwardnieves serummediatedcleavageofitalictoggleyesbacillusanthracisitalicprotectiveantigenisatwostepprocessthatinvolvesaserumcarboxypeptidase AT antonionakouzi serummediatedcleavageofitalictoggleyesbacillusanthracisitalicprotectiveantigenisatwostepprocessthatinvolvesaserumcarboxypeptidase AT johannarivera serummediatedcleavageofitalictoggleyesbacillusanthracisitalicprotectiveantigenisatwostepprocessthatinvolvesaserumcarboxypeptidase AT eieiphyu serummediatedcleavageofitalictoggleyesbacillusanthracisitalicprotectiveantigenisatwostepprocessthatinvolvesaserumcarboxypeptidase AT thanhtutwin serummediatedcleavageofitalictoggleyesbacillusanthracisitalicprotectiveantigenisatwostepprocessthatinvolvesaserumcarboxypeptidase AT jacquelinemachkar serummediatedcleavageofitalictoggleyesbacillusanthracisitalicprotectiveantigenisatwostepprocessthatinvolvesaserumcarboxypeptidase AT arturocasadevall serummediatedcleavageofitalictoggleyesbacillusanthracisitalicprotectiveantigenisatwostepprocessthatinvolvesaserumcarboxypeptidase
_version_	1718427937020051456

Serum-Mediated Cleavage of <italic toggle="yes">Bacillus anthracis</italic> Protective Antigen Is a Two-Step Process That Involves a Serum Carboxypeptidase

Ejemplares similares