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Functional and Transcriptome Analysis of Streptococcus pyogenes Virulence on Loss of Its Secreted Esterase

Esterases are broadly expressed in bacteria, but much remains unknown about their pathogenic effect. In previous studies, we focused on an esterase secreted by Streptococcus pyogenes (group A Streptococcus, GAS). Streptococcal secreted esterase (Sse) can hydrolyze the sn−2 ester bonds of platelet−ac...

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Autores principales: Zhang, Xiaolan, Wang, Yue, Zhu, Hui, Zhong, Zhaohua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9318535/
https://www.ncbi.nlm.nih.gov/pubmed/35887300
http://dx.doi.org/10.3390/ijms23147954
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author Zhang, Xiaolan
Wang, Yue
Zhu, Hui
Zhong, Zhaohua
author_facet Zhang, Xiaolan
Wang, Yue
Zhu, Hui
Zhong, Zhaohua
author_sort Zhang, Xiaolan
collection PubMed
description Esterases are broadly expressed in bacteria, but much remains unknown about their pathogenic effect. In previous studies, we focused on an esterase secreted by Streptococcus pyogenes (group A Streptococcus, GAS). Streptococcal secreted esterase (Sse) can hydrolyze the sn−2 ester bonds of platelet−activating factor (PAF), converting it to an inactive form that inhibits neutrophil chemotaxis to the infection sites. However, as a virulent protein, Sse probably participates in GAS pathogenesis far beyond chemotaxis inhibition. In this study, we generated the sse gene knockout strain (Δsse) from the parent strain MGAS5005 (hypervirulent M1T1 serotype) and compared the difference in phenotypes. Absence of Sse was related to weakened skin invasion in a murine infection model, and significantly reduced GAS epithelial adherence, invasion, and intracellular survival. Reduced virulence of the Δsse mutant strain was explored through transcriptome analysis, revealing a striking reduction in the abundance of invasive virulence factors including M protein, SIC, ScpA, and SclA. Besides the influence on the virulence, Sse also affected carbohydrate, amino acid, pyrimidine, and purine metabolism pathways. By elucidating Sse−mediated pathogenic process, the study will contribute to the development of new therapeutic agents that target bacterial esterases to control clinical GAS infections.
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spelling pubmed-93185352022-07-27 Functional and Transcriptome Analysis of Streptococcus pyogenes Virulence on Loss of Its Secreted Esterase Zhang, Xiaolan Wang, Yue Zhu, Hui Zhong, Zhaohua Int J Mol Sci Article Esterases are broadly expressed in bacteria, but much remains unknown about their pathogenic effect. In previous studies, we focused on an esterase secreted by Streptococcus pyogenes (group A Streptococcus, GAS). Streptococcal secreted esterase (Sse) can hydrolyze the sn−2 ester bonds of platelet−activating factor (PAF), converting it to an inactive form that inhibits neutrophil chemotaxis to the infection sites. However, as a virulent protein, Sse probably participates in GAS pathogenesis far beyond chemotaxis inhibition. In this study, we generated the sse gene knockout strain (Δsse) from the parent strain MGAS5005 (hypervirulent M1T1 serotype) and compared the difference in phenotypes. Absence of Sse was related to weakened skin invasion in a murine infection model, and significantly reduced GAS epithelial adherence, invasion, and intracellular survival. Reduced virulence of the Δsse mutant strain was explored through transcriptome analysis, revealing a striking reduction in the abundance of invasive virulence factors including M protein, SIC, ScpA, and SclA. Besides the influence on the virulence, Sse also affected carbohydrate, amino acid, pyrimidine, and purine metabolism pathways. By elucidating Sse−mediated pathogenic process, the study will contribute to the development of new therapeutic agents that target bacterial esterases to control clinical GAS infections. MDPI 2022-07-19 /pmc/articles/PMC9318535/ /pubmed/35887300 http://dx.doi.org/10.3390/ijms23147954 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhang, Xiaolan
Wang, Yue
Zhu, Hui
Zhong, Zhaohua
Functional and Transcriptome Analysis of Streptococcus pyogenes Virulence on Loss of Its Secreted Esterase
title Functional and Transcriptome Analysis of Streptococcus pyogenes Virulence on Loss of Its Secreted Esterase
title_full Functional and Transcriptome Analysis of Streptococcus pyogenes Virulence on Loss of Its Secreted Esterase
title_fullStr Functional and Transcriptome Analysis of Streptococcus pyogenes Virulence on Loss of Its Secreted Esterase
title_full_unstemmed Functional and Transcriptome Analysis of Streptococcus pyogenes Virulence on Loss of Its Secreted Esterase
title_short Functional and Transcriptome Analysis of Streptococcus pyogenes Virulence on Loss of Its Secreted Esterase
title_sort functional and transcriptome analysis of streptococcus pyogenes virulence on loss of its secreted esterase
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9318535/
https://www.ncbi.nlm.nih.gov/pubmed/35887300
http://dx.doi.org/10.3390/ijms23147954
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