SPD_0410 negatively regulates capsule polysaccharide synthesis and virulence in Streptococcus pneumoniae D39

Streptococcus pneumoniae capsular polysaccharide (CPS) is a crucial virulence factor for this pathogenic bacterium and is partially under transcriptional control. In this study, we used electrophoretic mobility shift assays and DNA enzyme footprinting to identified the hypothetical protein SPD_0410...

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Main Authors: Ye Tao, Li Lei, Shuhui Wang, Xuemei Zhang, Yibing Yin, Yuqiang Zheng
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Microbiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fmicb.2024.1513884/full
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author Ye Tao
Li Lei
Shuhui Wang
Xuemei Zhang
Yibing Yin
Yuqiang Zheng
author_facet Ye Tao
Li Lei
Shuhui Wang
Xuemei Zhang
Yibing Yin
Yuqiang Zheng
author_sort Ye Tao
collection DOAJ
description Streptococcus pneumoniae capsular polysaccharide (CPS) is a crucial virulence factor for this pathogenic bacterium and is partially under transcriptional control. In this study, we used electrophoretic mobility shift assays and DNA enzyme footprinting to identified the hypothetical protein SPD_0410 as a negative regulator of cps locus. Our results showed that the D39Δspd0410 mutant strain exhibited significantly elevated CPS levels compared to the parental strain D39s. SPD_0410 directly binds at two specific sites on the cps promoter. The regulatory effect of SPD_0410 on CPS was weakened after the mutation of specific binding sites in the promoter. RNAseq analysis revealed that the deletion of spd0410 led to alterations in glucose metabolism. However, the altered glucose levels appeared to eliminate the regulation of CPS synthesis by SPD_0410. Deleting the spd0410 gene resulted in higher invasion and phagocytic resistance of bacteria and in vivo mouse experiments confirmed that D39Δspd0410 caused more severe systemic disease than the parental strain D39s. Our results indicated that SPD_0410 negatively regulates the synthesis of S. pneumoniae capsules and can directly alter pneumococcal virulence.
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spelling doaj-art-ff54559088264beaab75d95cdbbbb0472025-01-03T06:47:32ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2025-01-011510.3389/fmicb.2024.15138841513884SPD_0410 negatively regulates capsule polysaccharide synthesis and virulence in Streptococcus pneumoniae D39Ye Tao0Li Lei1Shuhui Wang2Xuemei Zhang3Yibing Yin4Yuqiang Zheng5Department of Clinical Laboratory, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders and Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases, Chongqing, ChinaDepartment of Clinical Laboratory, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders and Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases, Chongqing, ChinaDujiangyan People’s Hospital, Chengdu, ChinaKey Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University, Chongqing, ChinaKey Laboratory of Diagnostic Medicine Designated by the Ministry of Education, Chongqing Medical University, Chongqing, ChinaDepartment of Clinical Laboratory, Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders and Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases, Chongqing, ChinaStreptococcus pneumoniae capsular polysaccharide (CPS) is a crucial virulence factor for this pathogenic bacterium and is partially under transcriptional control. In this study, we used electrophoretic mobility shift assays and DNA enzyme footprinting to identified the hypothetical protein SPD_0410 as a negative regulator of cps locus. Our results showed that the D39Δspd0410 mutant strain exhibited significantly elevated CPS levels compared to the parental strain D39s. SPD_0410 directly binds at two specific sites on the cps promoter. The regulatory effect of SPD_0410 on CPS was weakened after the mutation of specific binding sites in the promoter. RNAseq analysis revealed that the deletion of spd0410 led to alterations in glucose metabolism. However, the altered glucose levels appeared to eliminate the regulation of CPS synthesis by SPD_0410. Deleting the spd0410 gene resulted in higher invasion and phagocytic resistance of bacteria and in vivo mouse experiments confirmed that D39Δspd0410 caused more severe systemic disease than the parental strain D39s. Our results indicated that SPD_0410 negatively regulates the synthesis of S. pneumoniae capsules and can directly alter pneumococcal virulence.https://www.frontiersin.org/articles/10.3389/fmicb.2024.1513884/fullStreptococcus pneumoniaecapsular polysaccharidestranscriptional regulationcarbohydrate metabolismvirulence
spellingShingle Ye Tao
Li Lei
Shuhui Wang
Xuemei Zhang
Yibing Yin
Yuqiang Zheng
SPD_0410 negatively regulates capsule polysaccharide synthesis and virulence in Streptococcus pneumoniae D39
Frontiers in Microbiology
Streptococcus pneumoniae
capsular polysaccharides
transcriptional regulation
carbohydrate metabolism
virulence
title SPD_0410 negatively regulates capsule polysaccharide synthesis and virulence in Streptococcus pneumoniae D39
title_full SPD_0410 negatively regulates capsule polysaccharide synthesis and virulence in Streptococcus pneumoniae D39
title_fullStr SPD_0410 negatively regulates capsule polysaccharide synthesis and virulence in Streptococcus pneumoniae D39
title_full_unstemmed SPD_0410 negatively regulates capsule polysaccharide synthesis and virulence in Streptococcus pneumoniae D39
title_short SPD_0410 negatively regulates capsule polysaccharide synthesis and virulence in Streptococcus pneumoniae D39
title_sort spd 0410 negatively regulates capsule polysaccharide synthesis and virulence in streptococcus pneumoniae d39
topic Streptococcus pneumoniae
capsular polysaccharides
transcriptional regulation
carbohydrate metabolism
virulence
url https://www.frontiersin.org/articles/10.3389/fmicb.2024.1513884/full
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