Cargando…

A Novel Endogenous Inhibitor of the Secreted Streptococcal NAD-Glycohydrolase

The Streptococcus pyogenes NAD-glycohydrolase (SPN) is a toxic enzyme that is introduced into infected host cells by the cytolysin-mediated translocation pathway. However, how S. pyogenes protects itself from the self-toxicity of SPN had been unknown. In this report, we describe immunity factor for...

Descripción completa

Detalles Bibliográficos
Autores principales: Meehl, Michael A, Pinkner, Jerome S, Anderson, Patricia J, Hultgren, Scott J, Caparon, Michael G
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2005
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1298937/
https://www.ncbi.nlm.nih.gov/pubmed/16333395
http://dx.doi.org/10.1371/journal.ppat.0010035
_version_ 1782126264621989888
author Meehl, Michael A
Pinkner, Jerome S
Anderson, Patricia J
Hultgren, Scott J
Caparon, Michael G
author_facet Meehl, Michael A
Pinkner, Jerome S
Anderson, Patricia J
Hultgren, Scott J
Caparon, Michael G
author_sort Meehl, Michael A
collection PubMed
description The Streptococcus pyogenes NAD-glycohydrolase (SPN) is a toxic enzyme that is introduced into infected host cells by the cytolysin-mediated translocation pathway. However, how S. pyogenes protects itself from the self-toxicity of SPN had been unknown. In this report, we describe immunity factor for SPN (IFS), a novel endogenous inhibitor that is essential for SPN expression. A small protein of 161 amino acids, IFS is localized in the bacterial cytoplasmic compartment. IFS forms a stable complex with SPN at a 1:1 molar ratio and inhibits SPN's NAD-glycohydrolase activity by acting as a competitive inhibitor of its β-NAD(+) substrate. Mutational studies revealed that the gene for IFS is essential for viability in those S. pyogenes strains that express an NAD-glycohydrolase activity. However, numerous strains contain a truncated allele of ifs that is linked to an NAD-glycohydrolase−deficient variant allele of spn. Of practical concern, IFS allowed the normally toxic SPN to be produced in the heterologous host Escherichia coli to facilitate its purification. To our knowledge, IFS is the first molecularly characterized endogenous inhibitor of a bacterial β-NAD(+)−consuming toxin and may contribute protective functions in the streptococci to afford SPN-mediated pathogenesis.
format Text
id pubmed-1298937
institution National Center for Biotechnology Information
language English
publishDate 2005
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-12989372005-12-06 A Novel Endogenous Inhibitor of the Secreted Streptococcal NAD-Glycohydrolase Meehl, Michael A Pinkner, Jerome S Anderson, Patricia J Hultgren, Scott J Caparon, Michael G PLoS Pathog Research Article The Streptococcus pyogenes NAD-glycohydrolase (SPN) is a toxic enzyme that is introduced into infected host cells by the cytolysin-mediated translocation pathway. However, how S. pyogenes protects itself from the self-toxicity of SPN had been unknown. In this report, we describe immunity factor for SPN (IFS), a novel endogenous inhibitor that is essential for SPN expression. A small protein of 161 amino acids, IFS is localized in the bacterial cytoplasmic compartment. IFS forms a stable complex with SPN at a 1:1 molar ratio and inhibits SPN's NAD-glycohydrolase activity by acting as a competitive inhibitor of its β-NAD(+) substrate. Mutational studies revealed that the gene for IFS is essential for viability in those S. pyogenes strains that express an NAD-glycohydrolase activity. However, numerous strains contain a truncated allele of ifs that is linked to an NAD-glycohydrolase−deficient variant allele of spn. Of practical concern, IFS allowed the normally toxic SPN to be produced in the heterologous host Escherichia coli to facilitate its purification. To our knowledge, IFS is the first molecularly characterized endogenous inhibitor of a bacterial β-NAD(+)−consuming toxin and may contribute protective functions in the streptococci to afford SPN-mediated pathogenesis. Public Library of Science 2005-12 2005-12-02 /pmc/articles/PMC1298937/ /pubmed/16333395 http://dx.doi.org/10.1371/journal.ppat.0010035 Text en Copyright: © 2005 Meehl et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Meehl, Michael A
Pinkner, Jerome S
Anderson, Patricia J
Hultgren, Scott J
Caparon, Michael G
A Novel Endogenous Inhibitor of the Secreted Streptococcal NAD-Glycohydrolase
title A Novel Endogenous Inhibitor of the Secreted Streptococcal NAD-Glycohydrolase
title_full A Novel Endogenous Inhibitor of the Secreted Streptococcal NAD-Glycohydrolase
title_fullStr A Novel Endogenous Inhibitor of the Secreted Streptococcal NAD-Glycohydrolase
title_full_unstemmed A Novel Endogenous Inhibitor of the Secreted Streptococcal NAD-Glycohydrolase
title_short A Novel Endogenous Inhibitor of the Secreted Streptococcal NAD-Glycohydrolase
title_sort novel endogenous inhibitor of the secreted streptococcal nad-glycohydrolase
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1298937/
https://www.ncbi.nlm.nih.gov/pubmed/16333395
http://dx.doi.org/10.1371/journal.ppat.0010035
work_keys_str_mv AT meehlmichaela anovelendogenousinhibitorofthesecretedstreptococcalnadglycohydrolase
AT pinknerjeromes anovelendogenousinhibitorofthesecretedstreptococcalnadglycohydrolase
AT andersonpatriciaj anovelendogenousinhibitorofthesecretedstreptococcalnadglycohydrolase
AT hultgrenscottj anovelendogenousinhibitorofthesecretedstreptococcalnadglycohydrolase
AT caparonmichaelg anovelendogenousinhibitorofthesecretedstreptococcalnadglycohydrolase
AT meehlmichaela novelendogenousinhibitorofthesecretedstreptococcalnadglycohydrolase
AT pinknerjeromes novelendogenousinhibitorofthesecretedstreptococcalnadglycohydrolase
AT andersonpatriciaj novelendogenousinhibitorofthesecretedstreptococcalnadglycohydrolase
AT hultgrenscottj novelendogenousinhibitorofthesecretedstreptococcalnadglycohydrolase
AT caparonmichaelg novelendogenousinhibitorofthesecretedstreptococcalnadglycohydrolase