Antibody against Microbial Neuraminidases Recognizes Human Sialidase 3 (NEU3): the Neuraminidase/Sialidase Superfamily Revisited

ABSTRACT Neuraminidases (NAs) are critical virulence factors for several microbial pathogens. With a highly conserved catalytic domain, a microbial NA “superfamily” has been proposed. We previously reported that murine polymorphonuclear leukocyte (PMN) sialidase activity was important in leukocyte t...

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Autores principales:	Chiguang Feng, Jihong Li, Greg Snyder, Wei Huang, Simeon E. Goldblum, Wilbur H. Chen, Lai-Xi Wang, Bruce A. McClane, Alan S. Cross
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	Neu3 inflammation innate immunity neuraminidase sialidase Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/9d44252f5a7942d984e932742a4172a9
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spelling	oai:doaj.org-article:9d44252f5a7942d984e932742a4172a92021-11-15T15:51:28ZAntibody against Microbial Neuraminidases Recognizes Human Sialidase 3 (NEU3): the Neuraminidase/Sialidase Superfamily Revisited10.1128/mBio.00078-172150-7511https://doaj.org/article/9d44252f5a7942d984e932742a4172a92017-07-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00078-17https://doaj.org/toc/2150-7511ABSTRACT Neuraminidases (NAs) are critical virulence factors for several microbial pathogens. With a highly conserved catalytic domain, a microbial NA “superfamily” has been proposed. We previously reported that murine polymorphonuclear leukocyte (PMN) sialidase activity was important in leukocyte trafficking to inflamed sites and that antibodies to Clostridium perfringens NA recognized a cell surface molecule(s), presumed to be a sialidase of eukaryotic origin on interleukin-8-stimulated human and murine PMNs. These antibodies also inhibited cell sialidase activity both in vitro and, in the latter instance, in vivo. We therefore hypothesized that mammalian sialidases share structural homology and epitopes with microbial NAs. We now report that antibodies to one of the isoforms of C. perfringens NA, as well as anti-influenza virus NA serum, recognize human NEU3 but not NEU1 and that antibodies to C. perfringens NA inhibit NEU3 enzymatic activity. We conclude that the previously described microbial NA superfamily extends to human sialidases. Strategies designed to therapeutically inhibit microbial NA may need to consider potential compromising effects on human sialidases, particularly those expressed in cells of the immune system. IMPORTANCE We previously reported that sialidase activity of human neutrophils plays a critical role in the host inflammatory response. Since the catalytic domains of microbial neuraminidases are highly conserved, we hypothesized that antibodies against Clostridium perfringens neuraminidase might inhibit mammalian sialidase activity. Before the recognition of four mammalian sialidase (Neu) isoforms, we demonstrated that anti-C. perfringens neuraminidase antibodies inhibited human and murine sialidase activity in vivo and in vitro. We now show that the antibodies to microbial neuraminidase (C. perfringens and influenza virus) recognize human NEU3, which is important for neural development and cell signaling. Since many microbes that infect mucosal surfaces express neuraminidase, it is possible that the use of sialidase inhibitors (e.g., zanamivir), might also compromise human sialidase activity critical to the human immune response. Alternatively, sialidase inhibitors may prove useful in the treatment of hyperinflammatory conditions.Chiguang FengJihong LiGreg SnyderWei HuangSimeon E. GoldblumWilbur H. ChenLai-Xi WangBruce A. McClaneAlan S. CrossAmerican Society for MicrobiologyarticleNeu3inflammationinnate immunityneuraminidasesialidaseMicrobiologyQR1-502ENmBio, Vol 8, Iss 3 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neu3 inflammation innate immunity neuraminidase sialidase Microbiology QR1-502
spellingShingle	Neu3 inflammation innate immunity neuraminidase sialidase Microbiology QR1-502 Chiguang Feng Jihong Li Greg Snyder Wei Huang Simeon E. Goldblum Wilbur H. Chen Lai-Xi Wang Bruce A. McClane Alan S. Cross Antibody against Microbial Neuraminidases Recognizes Human Sialidase 3 (NEU3): the Neuraminidase/Sialidase Superfamily Revisited
description	ABSTRACT Neuraminidases (NAs) are critical virulence factors for several microbial pathogens. With a highly conserved catalytic domain, a microbial NA “superfamily” has been proposed. We previously reported that murine polymorphonuclear leukocyte (PMN) sialidase activity was important in leukocyte trafficking to inflamed sites and that antibodies to Clostridium perfringens NA recognized a cell surface molecule(s), presumed to be a sialidase of eukaryotic origin on interleukin-8-stimulated human and murine PMNs. These antibodies also inhibited cell sialidase activity both in vitro and, in the latter instance, in vivo. We therefore hypothesized that mammalian sialidases share structural homology and epitopes with microbial NAs. We now report that antibodies to one of the isoforms of C. perfringens NA, as well as anti-influenza virus NA serum, recognize human NEU3 but not NEU1 and that antibodies to C. perfringens NA inhibit NEU3 enzymatic activity. We conclude that the previously described microbial NA superfamily extends to human sialidases. Strategies designed to therapeutically inhibit microbial NA may need to consider potential compromising effects on human sialidases, particularly those expressed in cells of the immune system. IMPORTANCE We previously reported that sialidase activity of human neutrophils plays a critical role in the host inflammatory response. Since the catalytic domains of microbial neuraminidases are highly conserved, we hypothesized that antibodies against Clostridium perfringens neuraminidase might inhibit mammalian sialidase activity. Before the recognition of four mammalian sialidase (Neu) isoforms, we demonstrated that anti-C. perfringens neuraminidase antibodies inhibited human and murine sialidase activity in vivo and in vitro. We now show that the antibodies to microbial neuraminidase (C. perfringens and influenza virus) recognize human NEU3, which is important for neural development and cell signaling. Since many microbes that infect mucosal surfaces express neuraminidase, it is possible that the use of sialidase inhibitors (e.g., zanamivir), might also compromise human sialidase activity critical to the human immune response. Alternatively, sialidase inhibitors may prove useful in the treatment of hyperinflammatory conditions.
format	article
author	Chiguang Feng Jihong Li Greg Snyder Wei Huang Simeon E. Goldblum Wilbur H. Chen Lai-Xi Wang Bruce A. McClane Alan S. Cross
author_facet	Chiguang Feng Jihong Li Greg Snyder Wei Huang Simeon E. Goldblum Wilbur H. Chen Lai-Xi Wang Bruce A. McClane Alan S. Cross
author_sort	Chiguang Feng
title	Antibody against Microbial Neuraminidases Recognizes Human Sialidase 3 (NEU3): the Neuraminidase/Sialidase Superfamily Revisited
title_short	Antibody against Microbial Neuraminidases Recognizes Human Sialidase 3 (NEU3): the Neuraminidase/Sialidase Superfamily Revisited
title_full	Antibody against Microbial Neuraminidases Recognizes Human Sialidase 3 (NEU3): the Neuraminidase/Sialidase Superfamily Revisited
title_fullStr	Antibody against Microbial Neuraminidases Recognizes Human Sialidase 3 (NEU3): the Neuraminidase/Sialidase Superfamily Revisited
title_full_unstemmed	Antibody against Microbial Neuraminidases Recognizes Human Sialidase 3 (NEU3): the Neuraminidase/Sialidase Superfamily Revisited
title_sort	antibody against microbial neuraminidases recognizes human sialidase 3 (neu3): the neuraminidase/sialidase superfamily revisited
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/9d44252f5a7942d984e932742a4172a9
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Antibody against Microbial Neuraminidases Recognizes Human Sialidase 3 (NEU3): the Neuraminidase/Sialidase Superfamily Revisited

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