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Polyamine Synthesis Effects Capsule Expression by Reduction of Precursors in Streptococcus pneumoniae

Streptococcus pneumoniae (pneumococcus, Spn) colonizes the human nasopharynx asymptomatically but can cause infections such as otitis media, and invasive pneumococcal disease such as community-acquired pneumonia, meningitis, and sepsis. Although the success of Spn as a pathogen can be attributed to...

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Autores principales: Ayoola, Moses B., Shack, Leslie A., Nakamya, Mary F., Thornton, Justin A., Swiatlo, Edwin, Nanduri, Bindu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6727871/
https://www.ncbi.nlm.nih.gov/pubmed/31555234
http://dx.doi.org/10.3389/fmicb.2019.01996
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author Ayoola, Moses B.
Shack, Leslie A.
Nakamya, Mary F.
Thornton, Justin A.
Swiatlo, Edwin
Nanduri, Bindu
author_facet Ayoola, Moses B.
Shack, Leslie A.
Nakamya, Mary F.
Thornton, Justin A.
Swiatlo, Edwin
Nanduri, Bindu
author_sort Ayoola, Moses B.
collection PubMed
description Streptococcus pneumoniae (pneumococcus, Spn) colonizes the human nasopharynx asymptomatically but can cause infections such as otitis media, and invasive pneumococcal disease such as community-acquired pneumonia, meningitis, and sepsis. Although the success of Spn as a pathogen can be attributed to its ability to synthesize and regulate capsular polysaccharide (CPS) for survival in the host, the mechanisms of CPS regulation are not well-described. Recent studies from our lab demonstrate that deletion of a putative polyamine biosynthesis gene (ΔcadA) in Spn TIGR4 results in the loss of the capsule. In this study, we characterized the transcriptome and metabolome of ΔcadA and identified specific mechanisms that could explain the regulatory role of polyamines in pneumococcal CPS biosynthesis. Our data indicate that impaired polyamine synthesis impacts galactose to glucose interconversion via the Leloir pathway which limits the availability of UDP-galactose, a precursor of serotype 4 CPS, and UDP-N-acetylglucosamine (UDP-GlcNAc), a nucleotide sugar precursor that is at the intersection of CPS and peptidoglycan repeat unit biosynthesis. Reduced carbon flux through glycolysis, coupled with altered fate of glycolytic intermediates further supports impaired synthesis of UDP-GlcNAc. A significant increase in the expression of transketolases indicates a potential shift in carbon flow toward the pentose phosphate pathway (PPP). Higher PPP activity could constitute oxidative stress responses in ΔcadA which warrants further investigation. The results from this study clearly demonstrate the potential of polyamine synthesis, targeted for cancer therapy in human medicine, for the development of novel prophylactic and therapeutic strategies for treating bacterial infections.
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spelling pubmed-67278712019-09-25 Polyamine Synthesis Effects Capsule Expression by Reduction of Precursors in Streptococcus pneumoniae Ayoola, Moses B. Shack, Leslie A. Nakamya, Mary F. Thornton, Justin A. Swiatlo, Edwin Nanduri, Bindu Front Microbiol Microbiology Streptococcus pneumoniae (pneumococcus, Spn) colonizes the human nasopharynx asymptomatically but can cause infections such as otitis media, and invasive pneumococcal disease such as community-acquired pneumonia, meningitis, and sepsis. Although the success of Spn as a pathogen can be attributed to its ability to synthesize and regulate capsular polysaccharide (CPS) for survival in the host, the mechanisms of CPS regulation are not well-described. Recent studies from our lab demonstrate that deletion of a putative polyamine biosynthesis gene (ΔcadA) in Spn TIGR4 results in the loss of the capsule. In this study, we characterized the transcriptome and metabolome of ΔcadA and identified specific mechanisms that could explain the regulatory role of polyamines in pneumococcal CPS biosynthesis. Our data indicate that impaired polyamine synthesis impacts galactose to glucose interconversion via the Leloir pathway which limits the availability of UDP-galactose, a precursor of serotype 4 CPS, and UDP-N-acetylglucosamine (UDP-GlcNAc), a nucleotide sugar precursor that is at the intersection of CPS and peptidoglycan repeat unit biosynthesis. Reduced carbon flux through glycolysis, coupled with altered fate of glycolytic intermediates further supports impaired synthesis of UDP-GlcNAc. A significant increase in the expression of transketolases indicates a potential shift in carbon flow toward the pentose phosphate pathway (PPP). Higher PPP activity could constitute oxidative stress responses in ΔcadA which warrants further investigation. The results from this study clearly demonstrate the potential of polyamine synthesis, targeted for cancer therapy in human medicine, for the development of novel prophylactic and therapeutic strategies for treating bacterial infections. Frontiers Media S.A. 2019-08-29 /pmc/articles/PMC6727871/ /pubmed/31555234 http://dx.doi.org/10.3389/fmicb.2019.01996 Text en Copyright © 2019 Ayoola, Shack, Nakamya, Thornton, Swiatlo and Nanduri. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Ayoola, Moses B.
Shack, Leslie A.
Nakamya, Mary F.
Thornton, Justin A.
Swiatlo, Edwin
Nanduri, Bindu
Polyamine Synthesis Effects Capsule Expression by Reduction of Precursors in Streptococcus pneumoniae
title Polyamine Synthesis Effects Capsule Expression by Reduction of Precursors in Streptococcus pneumoniae
title_full Polyamine Synthesis Effects Capsule Expression by Reduction of Precursors in Streptococcus pneumoniae
title_fullStr Polyamine Synthesis Effects Capsule Expression by Reduction of Precursors in Streptococcus pneumoniae
title_full_unstemmed Polyamine Synthesis Effects Capsule Expression by Reduction of Precursors in Streptococcus pneumoniae
title_short Polyamine Synthesis Effects Capsule Expression by Reduction of Precursors in Streptococcus pneumoniae
title_sort polyamine synthesis effects capsule expression by reduction of precursors in streptococcus pneumoniae
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6727871/
https://www.ncbi.nlm.nih.gov/pubmed/31555234
http://dx.doi.org/10.3389/fmicb.2019.01996
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