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Glucose affects capsular polysaccharides synthesis via CcpA and HPr in Streptococcus pneumoniae
Rui Yang, Yapeng Zhang, Hong Wang, Hanyi Wang, Jiangming Xiao, Lian Li, Yuan Yuan, Yibing Yin, Xuemei Zhang
J. Microbiol. 2025;63(5):e2411024.   Published online May 27, 2025
DOI: https://doi.org/10.71150/jm.2411024
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AbstractAbstract PDFSupplementary Material

Streptococcus pneumoniae is a conditionally pathogenic bacteria that colonizes the nasopharynx of 27% to 65% of children and 10% of adults. Capsular polysaccharides are the most critical virulence factor of S. pneumoniae, and nonencapsulated strains are usually non-pathogenic. Previous studies have shown that glucose regulates capsule synthesis. To investigate the mechanism of carbon metabolism regulatory factors CcpA and HPr regulating capsule synthesis in the presence of glucose as the sole carbon source, we constructed deletion mutants (D39ΔccpA and ΔptsH) and complemented strains (D39ΔccpA::ccpA and ΔptsH::ptsH). In this study, we found that the promoting effect of capsule synthesis by glucose disappeared after the deletion of ccpA and ptsH, and demonstrated that the protein CcpA regulates capsule synthesis by binding to the cps promoter and altering the transcription level of the cps gene cluster. Increased glucose concentration up-regulated the level of HPr-Ser46~P, which enhanced the binding ability of CcpA to the DNA sequence of the cps promoter, thus promoting capsule synthesis. HPr also has a regulatory effect on capsule synthesis. These insights reveal a new synthesis mechanism of capsular polysaccharide and provide a new strategy of antibacterial drugs for S. pneumoniae.

Journal Articles
Genome Sequencing Highlights the Plant Cell Wall Degrading Capacity of Edible Mushroom Stropharia rugosoannulata
Mengpei Guo , Xiaolong Ma , Yan Zhou , Yinbing Bian , Gaolei Liu , Yingli Cai , Tianji Huang , Hongxia Dong , Dingjun Cai , Xueji Wan , Zhihong Wang , Yang Xiao , Heng Kang
J. Microbiol. 2023;61(1):83-93.   Published online February 1, 2023
DOI: https://doi.org/10.1007/s12275-022-00003-7
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AbstractAbstract
The basidiomycetous edible mushroom Stropharia rugosoannulata has excellent nutrition, medicine, bioremediation, and biocontrol properties. S. rugosoannulata has been widely and easily cultivated using agricultural by-products showing strong lignocellulose degradation capacity. However, the unavailable high-quality genome information has hindered the research on gene function and molecular breeding of S. rugosoannulata. This study provided a high-quality genome assembly and annotation from S. rugosoannulata monokaryotic strain QGU27 based on combined Illumina-Nanopore data. The genome size was about 47.97 Mb and consisted of 20 scaffolds, with an N50 of 3.73 Mb and a GC content of 47.9%. The repetitive sequences accounted for 17.41% of the genome, mostly long terminal repeats (LTRs). A total of 15,726 coding gene sequences were putatively identified with the BUSCO score of 98.7%. There are 142 genes encoding plant cell wall degrading enzymes (PCWDEs) in the genome, and 52, 39, 30, 11, 8, and 2 genes related to lignin, cellulose, hemicellulose, pectin, chitin, and cutin degradation, respectively. Comparative genomic analysis revealed that S. rugosoannulata is superior in utilizing aldehyde-containing lignins and is possible to utilize algae during the cultivation.

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Citations to this article as recorded by  
  • Analysis of Gene Regulatory Network and Transcription Factors in Different Tissues of the Stropharia rugosoannulata Fruiting Body
    Jia Lu, Jing Yan, Na Lu, Jiling Song, Jiayao Lin, Xiaohua Zhou, Xuebing Ying, Zhen Li, Zufa Zhou, Fangjie Yao
    Journal of Fungi.2025; 11(2): 123.     CrossRef
  • Evaluation of Genetic Diversity and Agronomic Traits of Germplasm Resources of Stropharia rugosoannulata
    Miao Gu, Qiang Chen, Yan Zhang, Yongchang Zhao, Li Wang, Xiangli Wu, Mengran Zhao, Wei Gao
    Horticulturae.2024; 10(3): 213.     CrossRef
  • Molecular Profiling of Rice Straw Degradability Discrepancy in Stropharia rugosoannulata Core Germplasm
    Wenbing Gong, Yuyu Zeng, Xinru Li, Zhidong Zhao, Nan Shen, Yan Zhou, Yinbing Bian, Yang Xiao
    Journal of Agricultural and Food Chemistry.2024; 72(45): 25379.     CrossRef
  • Genome assembly of M. spongiola and comparative genomics of the genus Morchella provide initial insights into taxonomy and adaptive evolution
    Qing Meng, Zhanling Xie, Hongyan Xu, Jing Guo, Qingqing Peng, Yanyan Li, Jiabao Yang, Deyu Dong, Taizhen Gao, Fan Zhang
    BMC Genomics.2024;[Epub]     CrossRef
Functional analysis of ascP in Aeromonas veronii TH0426 reveals a key role in the regulation of virulence
Yongchao Guan , Meng Zhang , Yingda Wang , Zhongzhuo Liu , Zelin Zhao , Hong Wang , Dingjie An , Aidong Qian , Yuanhuan Kang , Wuwen Sun , Xiaofeng Shan
J. Microbiol. 2022;60(12):1153-1161.   Published online November 10, 2022
DOI: https://doi.org/10.1007/s12275-022-2373-8
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AbstractAbstract
Aeromonas veronii is a pathogen which can induce diseases in humans, animals and aquatic organisms, but its pathogenic mechanism and virulence factors are still elusive. In this study, we successfully constructed a mutant strain (ΔascP) by homologous recombination. The results showed that the deletion of the ascP gene significantly down-regulated the expression of associated effector proteins in A. veronii compared to its wild type. The adhesive and invasive abilities of ΔascP to EPC cells were 0.82-fold lower in contrast to the wild strain. The toxicity of ΔascP to cells was decreased by about 2.91-fold (1 h) and 1.74-fold (2 h). Furthermore, the LD50 of the mutant strain of crucian carp was reduced by 19.94-fold, and the virulence was considerably attenuated. In contrast to the wild strain, the ΔascP content in the liver and spleen was considerably lower. The titers of serum cytokines (IL-8, TNF-α, and IL-1β) in crucian carp after the infection of the ΔascP strain were considerably lower in contrast to the wild strain. Hence, the ascP gene is essential for the etiopathogenesis of A. veronii TH0426.

Citations

Citations to this article as recorded by  
  • Complete genome sequence and genome-wide transposon mutagenesis enable the determination of genes required for sodium hypochlorite tolerance and drug resistance in pathogen Aeromonas veronii GD2019
    Yifan Bu, Chengyu Liu, Yabo Liu, Wensong Yu, Tingjin Lv, Yuanxing Zhang, Qiyao Wang, Yue Ma, Shuai Shao
    Microbiological Research.2024; 284: 127731.     CrossRef
  • Construction of the flagellin F mutant of Vibrio parahaemolyticus and its toxic effects on silver pomfret (Pampus argenteus) cells
    Yang Li, Chao Liu, Yuechen Sun, Ruijun Wang, Choufei Wu, Hanqu Zhao, Liqin Zhang, Dawei Song, Quanxin Gao
    International Journal of Biological Macromolecules.2024; 259: 129395.     CrossRef
  • Ferric uptake regulator (fur) affects the pathogenicity of Aeromonas veronii TH0426 by regulating flagellar assembly and biofilm formation
    Jin-shuo Gong, Ying-da Wang, Yan-long Jiang, Di Zhang, Ya-nan Cai, Xiao-feng Shan, He Gong, Hao Dong
    Aquaculture.2024; 580: 740361.     CrossRef
Discovery of novel glycoside hydrolases from C-glycoside-degrading bacteria using sequence similarity network analysis
Bin Wei , Ya-Kun Wang , Jin-Biao Yu , Si-Jia Wang , Yan-Lei Yu , Xue-Wei Xu , Hong Wang
J. Microbiol. 2021;59(10):931-940.   Published online September 23, 2021
DOI: https://doi.org/10.1007/s12275-021-1292-4
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AbstractAbstract
C-Glycosides are an important type of natural product with significant bioactivities, and the C-glycosidic bonds of C-glycosides can be cleaved by several intestinal bacteria, as exemplified by the human faeces-derived puerarin-degrading bacterium Dorea strain PUE. However, glycoside hydrolases in these bacteria, which may be involved in the C-glycosidic bond cleavage of C-glycosides, remain largely unknown. In this study, the genomes of the closest phylogenetic neighbours of five puerarin-degrading intestinal bacteria (including Dorea strain PUE) were retrieved, and the protein-coding genes in the genomes were subjected to sequence similarity network (SSN) analysis. Only four clusters of genes were annotated as glycoside hydrolases and observed in the genome of D. longicatena DSM 13814T (the closest phylogenetic neighbour of Dorea strain PUE); therefore, genes from D. longicatena DSM 13814T belonging to these clusters were selected to overexpress recombinant proteins (CG1, CG2, CG3, and CG4) in Escherichia coli BL21(DE3). In vitro assays indicated that CG4 efficiently cleaved the O-glycosidic bond of daidzin and showed moderate β-D-glucosidase and β-D-xylosidase activity. CG2 showed weak activity in hydrolyzing daidzin and pNP- β-D-fucopyranoside, while CG3 was identified as a highly selective and efficient α-glycosidase. Interestingly, CG3 and CG4 could be selectively inhibited by daidzein, explaining their different performance in kinetic studies. Molecular docking studies predicted the molecular determinants of CG2, CG3, and CG4 in substrate selectivity and inhibition propensity. The present study identified three novel and distinctive glycoside hydrolases, highlighting the potential of SSN in the discovery of novel enzymes from genomic data.

Citations

Citations to this article as recorded by  
  • Two-step computational redesign of Bacillus subtilis cellulase and β-glucanase for enhanced thermostability and activity
    Huan Zhang, Tong Zhu, Qinglin Zhai, Qiansi Chen, Xuanshuo Zhang, Yiqiang Chen, Wei He, Jingjing Li, Jianqiang Fan, Jiemeng Tao, Xingchuan Hu, Lingfeng Qi, Chaochao Wang, Kuanqi Liao, Yanchun Chen, Yinglu Cui, Shanyi Chen, Bian Wu
    International Journal of Biological Macromolecules.2025; 285: 138274.     CrossRef
  • A newly isolated human intestinal strain deglycosylating flavonoid C-glycosides
    Sha Wang, Siqi Liu, Jing Wang, Jiayue Tao, Mengjiao Wu, Wenfu Ma, Rufeng Wang
    Archives of Microbiology.2022;[Epub]     CrossRef
The role of Jacalin-related lectin gene AOL_s00083g511 in the development and pathogenicity of the nematophagous fungus Arthrobotrys oligospora
Xinyuan Dong , Jiali Si , Guanghui Zhang , Zhen Shen , Li Zhang , Kangliang Sheng , Jingmin Wang , Xiaowei Kong , Xiangdong Zha , Yongzhong Wang
J. Microbiol. 2021;59(8):736-745.   Published online July 5, 2021
DOI: https://doi.org/10.1007/s12275-021-1029-4
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AbstractAbstract
Arthrobotrys oligospora is a model species of nematophagous fungi and has great potential for the biological control of nematode diseases. Lectin is a protein that binds to carbohydrates and their complexes with high specificity, which mediates recognition events in various physiological and pathological processes. This study aimed to investigate the role of the Jacalin-related lectin (JRL) gene, AOL_s00083g511, in A. oligospora development. Through a homology recombination approach, we obtained the AOL_s00083g511 knockout mutant strain (Δg511). Next, the biological characteristics of the Δg511 mutant strain, including growth rate, conidia germination rate, adaptation to environmental stresses, and nematocidal activity, were compared with those of the wild-type (WT) strain. The results showed that the JRL gene AOL_ s00083g511 did not affect fungal growth, conidia germination, 3D-trap formation, and the ability of A. oligospora to prey on nematodes significantly. We speculate that this phenomenon may be caused by a loss of the key β1–β2 loops in the AOL_ s00083g511-encoded JRL domain and an intrinsic genetic compensation of AOL_s00083g511 in this fungus. The growth rates of both strains on high salt or surfactant media were similar; however, in the strong oxidation medium, the growth rate of the Δg511 mutant was significantly lower than that of the WT strain, indicating that AOL_s00083g511 might play a role in oxidative stress resistance. These findings provide a basis for further analysis of the related functions of the JRL gene in A. oligospora and their potential roles in the biological control of nematodes in the future.

Citations

Citations to this article as recorded by  
  • Function discovery of a non-ribosomal peptide synthetase-like encoding gene in the nematode-trapping fungus Arthrobotrys oligospora
    Tiantian Gu, Hengqian Lu, Huiwen Liu, Guanghui Zhang, Yongzhong Wang
    Frontiers in Microbiology.2023;[Epub]     CrossRef
  • The fucose-specific lectin gene AOL_s00054g276 affects trap formation and nematocidal activity of the nematophagous fungus Arthrobotrys oligospora
    Jiali Si, Xinyuan Dong, Guanghui Zhang, Hengqian Lu, Kaijing Tang, Li Zhang, Xiaowei Kong, Kangliang Sheng, Jingmin Wang, Xiangdong Zha, Yongzhong Wang
    FEMS Microbiology Letters.2022;[Epub]     CrossRef
  • Phospholipase C (AoPLC2) regulates mycelial development, trap morphogenesis, and pathogenicity of the nematode-trapping fungus Arthrobotrys oligospora
    Meihua Xie, Ni Ma, Na Bai, Meichen Zhu, Ke-Qin Zhang, Jinkui Yang
    Journal of Applied Microbiology.2022; 132(3): 2144.     CrossRef
Streptococcus pneumoniae aminopeptidase N contributes to bacterial virulence and elicits a strong innate immune response through MAPK and PI3K/AKT signaling
Ling Wang , Xuemei Zhang , Guangying Wu , Yuhong Qi , Jinghui Zhang , Jing Yang , Hong Wang , Wenchun Xu
J. Microbiol. 2020;58(4):330-339.   Published online February 27, 2020
DOI: https://doi.org/10.1007/s12275-020-9538-0
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AbstractAbstract
Streptococcus pneumoniae is a Gram-positive pathogen with high morbidity and mortality globally but some of its pathogenesis remains unknown. Previous research has provided evidence that aminopeptidase N (PepN) is most likely a virulence factor of S. pneumoniae. However, its role in S. pneumoniae virulence and its interaction with the host remains to be confirmed. We generated a pepN gene deficient mutant strain and found that its virulence for mice was significantly attenuated as were in vitro adhesion and invasion of host cells. The PepN protein could induce a strong innate immune response in vivo and in vitro and induced secretion of IL-6 and TNF-α by primary peritoneal macrophages via the rapid phosphorylation of MAPK and PI3K/AKT signaling pathways and this was confirmed using specific pathway inhibitors. In conclusion, PepN is a novel virulence factor that is essential for the virulence of S. pneumoniae and induces host innate immunity via MAPK and PI3K/AKT signaling.

Citations

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  • Maternal immune activation mediated prenatal chronic stress induces Th17/Treg cell imbalance may relate to the PI3K/Akt/NF-κB signaling pathway in offspring rats
    Ye Li, Guixiang Yao, Rui Wang, Jiashu Zhu, Hongyu Li, Deguang Yang, Shuqin Ma, Youjuan Fu, Can Liu, Suzhen Guan
    International Immunopharmacology.2024; 126: 111308.     CrossRef
  • Secreted protein NFA47630 from Nocardia farcinica IFM10152 induces immunoprotective effects in mice
    Lichao Han, Xingzhao Ji, Shihong Fan, Jirao Shen, Bin Liang, Zhenjun Li
    Tropical Diseases, Travel Medicine and Vaccines.2024;[Epub]     CrossRef
  • Human microbiomes in cancer development and therapy
    Chenglai Xia, Jiyan Su, Can Liu, Zhikai Mai, Shuanghong Yin, Chuansheng Yang, Liwu Fu
    MedComm.2023;[Epub]     CrossRef
  • Identification and Analysis of Potential Immune-Related Biomarkers in Endometriosis
    Yanan He, Jixin Li, Yanjun Qu, Liyuan Sun, Xibo Zhao, Han Wu, Guangmei Zhang, Amar Singh
    Journal of Immunology Research.2023; 2023: 1.     CrossRef
  • The identification of two M20B family peptidases required for full virulence in Staphylococcus aureus
    Nathanial J. Torres, Devon N. Rizzo, Maria A. Reinberg, Mary-Elizabeth Jobson, Brendan C. Totzke, Jessica K. Jackson, Wenqi Yu, Lindsey N. Shaw
    Frontiers in Cellular and Infection Microbiology.2023;[Epub]     CrossRef
  • Exploration of immune response mechanisms in cadmium and copper co-exposed juvenile golden cuttlefish (Sepia esculenta) based on transcriptome profiling
    Xiaokai Bao, Weijun Wang, Xipan Chen, Yanwei Feng, Xiaohui Xu, Guohua Sun, Bin Li, Xiumei Liu, Zan Li, Jianmin Yang
    Frontiers in Immunology.2022;[Epub]     CrossRef
  • Pathogenicity and virulence ofStreptococcus pneumoniae: Cutting to the chase on proteases
    Mary E. Marquart
    Virulence.2021; 12(1): 766.     CrossRef
  • Gut-Lung Microbiota in Chronic Pulmonary Diseases: Evolution, Pathogenesis, and Therapeutics
    Chang Yi Shi, Chen Huan Yu, Wen Ying Yu, Hua Zhong Ying, Hua Zhang
    Canadian Journal of Infectious Diseases and Medical Microbiology.2021; 2021: 1.     CrossRef
Research Support, Non-U.S. Gov'ts
Screening and Identification of ClpE Interaction Proteins in Streptococcus pneumoniae by a Bacterial Two-Hybrid System and Co-immunoprecipitation
WenJuan Yan , YingYing Cai , Qun Zhang , YuSi Liu , WenChun Xu , YiBing Yin , YuJuan He , Hong Wang , XueMei Zhang
J. Microbiol. 2013;51(4):453-460.   Published online August 30, 2013
DOI: https://doi.org/10.1007/s12275-013-3001-4
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AbstractAbstract
Hsp100/Clp proteins have crucial functions in the protein quality control, stress tolerance, and virulence of many pathogenic bacteria. ClpE is an important virulence factor involved in adherence and invasion in Streptococcus pneumoniae. To explore the underlying mechanism, we screened ClpE interaction proteins using a bacterial two-hybrid system and co-immunoprecipitation. We used ClpE as bait and constructed the pBT-ClpE bait plasmid for two-hybrid screening. Then, we constructed ClpE::GFP fusion for co-immunoprecipitation screening using anti-GFP monoclonal antibody. We obtained eight potential ClpE interaction proteins, including carbamoyl-phosphate synthase, pyruvate oxidase (SpxB), phosphoenolpyruvate-protein phosphotransferase, aminopeptidase N (pepN), L-lactate dehydrogenase, ribosomal protein S4, sensor histidine kinase (SPD_2019), and FtsW (a cell division protein). FtsW, SpxB, pepN, and SPD_2019 were confirmed to interact with ClpE using Bacterial Two-hybrid or Co-immunoprecipitation. Morphologic observations found that ΔclpE strain existed in abnormal division. β-Galactosidase activity assay suggested that ClpE contributed to the degradation of FtsW. Furthermore, FtsW could be induced by heat shock. The results suggested that ClpE might affect cell division by regulating the level of FtsW. These data may provide new insights in studying the role of ClpE in S. pneumoniae.
SP0454, A Putative Threonine Dehydratase, Is Required For Pneumococcal Virulence In Mice
WenJuan Yan , Hong Wang , WenChun Xu , KaiFeng Wu , Run Yao , XiuYu Xu , Jie Dong , YanQing Zhang , Wen Zhong , XueMei Zhang
J. Microbiol. 2012;50(3):511-517.   Published online June 30, 2012
DOI: https://doi.org/10.1007/s12275-012-2014-8
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AbstractAbstract
Increasing pressure in antibiotic resistance and the requirement for the design of new vaccines are the objectives of clarifying the putative virulence factors in pneumococcal infection. In this study, the putative threonine dehydratase sp0454 was inactivated by erythromycin-resistance cassette replacement in Streptococcus pneumoniae CMCC 31203 strain. The sp0454 mutant was tested for cell growth, adherence, colonization, and virulence in a murine model. The Δsp0454 mutant showed decreased ability for colonization and impaired ability to adhere to A549 cells. However, the SP0454 polypeptide or its antiserum did not affect pneumococcal CMCC 31203 adhesion to A549 cells. The sp0454 deletion mutant was less virulent in a murine intranasal infection model. Real-time RT-PCR analysis revealed significant decrease of the pneumococcal surface antigen A expression in the sp0454 mutant. These results suggest that SP0454 contributes to virulence and colonization, which could be explained in part by modulating the expression of other virulence factors, such as psaA in pneumococcal infection.

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