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Advances in functional analysis of the microbiome: Integrating metabolic modeling, metabolite prediction, and pathway inference with Next-Generation Sequencing data
Sungwon Jung
J. Microbiol. 2025;63(1):e.2411006.   Published online January 24, 2025
DOI: https://doi.org/10.71150/jm.2411006
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AbstractAbstract PDF

This review explores current advancements in microbiome functional analysis enabled by next-generation sequencing technologies, which have transformed our understanding of microbial communities from mere taxonomic composition to their functional potential. We examine approaches that move beyond species identification to characterize microbial activities, interactions, and their roles in host health and disease. Genome-scale metabolic models allow for in-depth simulations of metabolic networks, enabling researchers to predict microbial metabolism, growth, and interspecies interactions in diverse environments. Additionally, computational methods for predicting metabolite profiles offer indirect insights into microbial metabolic outputs, which is crucial for identifying biomarkers and potential therapeutic targets. Functional pathway analysis tools further reveal microbial contributions to metabolic pathways, highlighting alterations in response to environmental changes and disease states. Together, these methods offer a powerful framework for understanding the complex metabolic interactions within microbial communities and their impact on host physiology. While significant progress has been made, challenges remain in the accuracy of predictive models and the completeness of reference databases, which limit the applicability of these methods in under-characterized ecosystems. The integration of these computational tools with multi-omic data holds promise for personalized approaches in precision medicine, allowing for targeted interventions that modulate the microbiome to improve health outcomes. This review highlights recent advances in microbiome functional analysis, providing a roadmap for future research and translational applications in human health and environmental microbiology.

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  • Microbiota, chronic inflammation, and health: The promise of inflammatome and inflammatomics for precision medicine and healthcare
    Huan Zhang, Bing Jun Yang Lee, Tong Wang, Xuesong Xiang, Yafang Tan, Yanping Han, Yujing Bi, Fachao Zhi, Xin Wang, Fang He, Seppo J. Salminen, Baoli Zhu, Ruifu Yang
    hLife.2025;[Epub]     CrossRef
Journal Articles
Comparative Secretory Efficiency of Two Chitosanase Signal Peptides from Bacillus subtilis in Escherichia coli
Tae-Yang Eom, Yehui Gang, Youngdeuk Lee, Yoon-Hyeok Kang, Eunyoung Jo, Svini Dileepa Marasinghe, Heung Sik Park, Gun-Hoo Park, Chulhong Oh
J. Microbiol. 2024;62(12):1155-1164.   Published online November 25, 2024
DOI: https://doi.org/10.1007/s12275-024-00186-1
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AbstractAbstract
The production of recombinant proteins in Escherichia coli is often challenged by cytoplasmic expression due to proteolytic degradation and inclusion body formation. Extracellular expression can overcome these problems by simplifying downstream processing and improving protein yields. This study aims to compare the efficiency of two Bacillus subtilis chitosanase signal peptides in mediating extracellular secretion in E. coli. We identified a naturally occurring mutant signal peptide (mCsn2-SP) from B. subtilis CH2 chitosanase (CH2CSN), which is characterized by a deletion of six amino acids in the N-region relative to the signal peptide (Csn1-SP) from B. subtilis CH1 chitosanase (CH1CSN). The CH1CSN and CH2CSN genes were cloned into the pET-11a vector and protein secretion was evaluated in E. coli BL21(DE3) host cells. Expression was induced with 0.1 mM and 1 mM isopropyl β-D-1-thiogalactopyranoside (IPTG) at 30 °C for one and three days. CH2CSN showed higher secretion levels compared to CH1CSN under all experimental conditions, especially with 0.1 mM IPTG induction for 3 days, which resulted in a 2.37-fold increase in secretion. Furthermore, it was demonstrated that mCsn2-SP is capable of secreting human Cu,Zn-superoxide dismutase (hSOD) in E. coli BL21(DE3) and successfully translocating it to the periplasmic region. This study represents the inaugural investigation into the utilisation of a naturally modified signal peptide, thereby corroborating the assertion that signal peptide deletion variants can influence protein secretion efficiency. Furthermore, the findings substantiate the proposition that such variants can serve as a viable alternative for the secretion of heterologous proteins in E. coli.
Investigation of Bottleneck Enzyme Through Flux Balance Analysis to Improve Glycolic Acid Production in Escherichia coli
Jungyeon Kim, Ye-Bin Kim, Ju-Young Kim, Min-Ju Seo, Soo-Jin Yeom, Bong Hyun Sung
J. Microbiol. 2024;62(11):1023-1033.   Published online October 28, 2024
DOI: https://doi.org/10.1007/s12275-024-00175-4
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AbstractAbstract
Amid rising environmental concerns, attempts have been made to produce glycolic acid (GA) using microbial processes with renewable carbon resources instead of using chemicals. The Dahms pathway for GA production uses xylose as a substrate and consists of relatively simple enzymatic steps. However, employing it leads to a decrease in cell growth and GA productivity. Systematically identifying and addressing metabolic bottlenecks in the Dahms pathway are essential for efficient glycolic acid (GA) production have not yet been performed. Through metabolic flux balance analysis, we found that insufficient aldehyde dehydrogenase (AldA) activity lowers GA production and negatively affects cell growth due to reduced energy production. Thus, we discovered a novel AldA isolated from Buttiauxella agrestis (BaAldA) demonstrated a 1.69-fold lower KM and a 1.49-fold higher turnover rate (kcat/KM) than AldA from Escherichia coli (EcAldA). GA production in E. coli harboring BaAldA was 1.59 times higher than in the original strain. Fed-batch fermentation of E. coli harboring BaAldA produced 22.70 g/L GA with a yield of 0.497 g/gxylose (98.2% of the theoretical maximum yield in the Dahms pathway), showing a higher final yield for GA than previously reported in E. coli. Our novel BaAldA enzyme shows great potential for the production of GA using microorganisms or enzymes. Furthermore, our approach to identifying metabolic bottlenecks using flux balance analysis could be utilized to enhance the microbial production of various desirable products in future studies.
In Silico Intensive Analysis for the E4 Gene Evolution of Human Adenovirus Species D
Chanhee Lee, Anyeseu Park, Jeong Yoon Lee
J. Microbiol. 2024;62(5):409-418.   Published online April 30, 2024
DOI: https://doi.org/10.1007/s12275-024-00132-1
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AbstractAbstract
Adenovirus (Ad) is a ubiquitous pathogen capable of infecting a wide range of animals and humans. Human Adenovirus (HAdV) can cause severe infection, particularly in individuals with compromised immune systems. To date, over 110 types of HAdV have been classified into seven species from A to G, with the majority belonging to the human adenovirus species D (HAdV-D). In the HAdV-D, the most significant factor for the creation of new adenovirus types is homologous recombination between viral genes involved in determining the virus tropism or evading immune system of host cells. The E4 gene, consisting of seven Open Reading Frames (ORFs), plays a role in both the regulation of host cell metabolism and the replication of viral genes. Despite long-term studies, the function of each ORF remains unclear. Based on our updated information, ORF2, ORF3, and ORF4 have been identified as regions with relatively high mutations compared to other ORFs in the E4 gene, through the use of in silico comparative analysis. Additionally, we managed to visualize high mutation sections, previously undetectable at the DNA level, through a powerful amino acid sequence analysis tool known as proteotyping. Our research has revealed the involvement of the E4 gene in the evolution of human adenovirus, and has established accurate sequence information of the E4 gene, laying the groundwork for further research.
CA‑CAS‑01‑A: A Permissive Cell Line for Isolation and Live Attenuated Vaccine Development Against African Swine Fever Virus
Seung-Chul Lee , Yongkwan Kim , Ji-Won Cha , Kiramage Chathuranga , Niranjan Dodantenna , Hyeok-Il Kwon , Min Ho Kim , Weonhwa Jheong , In-Joong Yoon , Joo Young Lee , Sung-Sik Yoo , Jong-Soo Lee
J. Microbiol. 2024;62(2):125-134.   Published online March 13, 2024
DOI: https://doi.org/10.1007/s12275-024-00116-1
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AbstractAbstract
African swine fever virus (ASFV) is the causative agent of the highly lethal African swine fever disease that affects domestic pigs and wild boars. In spite of the rapid spread of the virus worldwide, there is no licensed vaccine available. The lack of a suitable cell line for ASFV propagation hinders the development of a safe and effective vaccine. For ASFV propagation, primary swine macrophages and monocytes have been widely studied. However, obtaining these cells can be time-consuming and expensive, making them unsuitable for mass vaccine production. The goal of this study was to validate the suitability of novel CA-CAS-01-A (CAS-01) cells, which was identified as a highly permissive cell clone for ASFV replication in the MA-104 parental cell line for live attenuated vaccine development. Through a screening experiment, maximum ASFV replication was observed in the CAS-01 cell compared to other sub-clones of MA-104 with 14.89 and log10 7.5 ± 0.15 Ct value and TCID50/ ml value respectively. When CAS-01 cells are inoculated with ASFV, replication of ASFV was confirmed by Ct value for ASFV DNA, HAD50/ ml assay, TCID50/ ml assay, and cytopathic effects and hemadsoption were observed similar to those in primary porcine alveolar macrophages after 5th passage. Additionally, we demonstrated stable replication and adaptation of ASFV over the serial passage. These results suggest that CAS-01 cells will be a valuable and promising cell line for ASFV isolation, replication, and development of live attenuated vaccines.

Citations

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  • Development and characterization of high-efficiency cell-adapted live attenuated vaccine candidate against African swine fever
    Min Ho Kim, Ashan Subasinghe, Yongkwan Kim, Hyeok-Il Kwon, Yehjin Cho, Kiramage Chathuranga, Ji-Won Cha, Ji-Yoon Moon, Ji-Hyeon Hong, Jin Kim, Seung-Chul Lee, Niranjan Dodantenna, Nuwan Gamage, W. A. Gayan Chathuranga, Yeonji Kim, In-Joong Yoon, Joo Young
    Emerging Microbes & Infections.2024;[Epub]     CrossRef
Review
The Fatal Role of Enterohaemorrhagic Escherichia coli Shiga Toxin‑associated Extracellular Vesicles in Host Cells
Kyung-Soo Lee , Jun-Young Park , Yu-Jin Jeong , Moo-Seung Lee
J. Microbiol. 2023;61(8):715-727.   Published online September 4, 2023
DOI: https://doi.org/10.1007/s12275-023-00066-0
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AbstractAbstract
Enterohemorrhagic Escherichia coli (EHEC) is a specific subset of Shiga toxin-producing Escherichia coli (STEC) strains that are characterized by their ability to cause bloody diarrhea (hemorrhagic colitis) and potentially life-threatening, extraintestinal complications such as hemolytic uremic syndrome (HUS), which is associated with acute renal failure., contributing to severe clinical outcomes. The Shiga toxins (Stxs), produced by EHEC, are primary virulence factors. These potent cytotoxins are composed of one enzymatically active A subunit (StxA) and five receptor-binding B subunits (StxB). Although the toxins are primarily associated with cytotoxic effects, they also elicit other pathogenic consequences due to their induction of a number of biological processes, including apoptosis through ER-stress, pro-inflammatory responses, autophagy, and post-translational modification (PTM). Moreover, several studies have reported the association between Stxs and extracellular vesicles (EVs), including microvesicles and exosomes, demonstrating that Stx-containing EVs secreted by intoxicated macrophages are taken up by recipient cells, such as toxin-sensitive renal proximal tubular epithelial cells. This mechanism likely contributes to the spreading of Stxs within the host, and may exacerbate gastrointestinal illnesses and kidney dysfunction. In this review, we summarize recent findings relating to the host responses, in different types of cells in vitro and in animal models, mediated by Stxs-containing exosomes. Due to their unique properties, EVs have been explored as therapeutic agents, drug delivery systems, and diagnostic tools. Thus, potential therapeutic applications of EVs in EHEC Stxs-mediated pathogenesis are also briefly reviewed.

Citations

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  • Estimation of IL-8 and TNF-α Levels in Pediatric Diarrhea Patients Infected with Enterohemorrhagic E. coli O157:H7
    Safaa A. AL-Isawi, Shaimaa Jassim Alsultany
    Medical Journal of Babylon.2024; 21(3): 533.     CrossRef
  • Structural basis to identify a target site in Shiga toxin for the inhibitor discovery against growth of Shiga toxin-producing E. coli
    Anuja Prabhudesai, Samir Shaikh, Kayasth Zarna Ashwinbhai, Reeshu Gupta
    Bulletin of the National Research Centre.2024;[Epub]     CrossRef
Journal Articles
Mst1/2-ALK promotes NLRP3 inflammasome activation and cell apoptosis during Listeria monocytogenes infection
Aijiao Gao , Huixin Tang , Qian Zhang , Ruiqing Liu , Lin Wang , Yashan Liu , Zhi Qi , Yanna Shen
J. Microbiol. 2021;59(7):681-692.   Published online April 20, 2021
DOI: https://doi.org/10.1007/s12275-021-0638-2
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AbstractAbstract
Listeria monocytogenes (L. monocytogenes) is a Gram-positive intracellular foodborne pathogen that causes severe diseases, such as meningitis and sepsis. The NLR family pyrin domain-containing 3 (NLRP3) inflammasome has been reported to participate in host defense against pathogen infection. However, the exact molecular mechanisms underlying NLRP3 inflammasome activation remain to be fully elucidated. In the present study, the roles of mammalian Ste20- like kinases 1/2 (Mst1/2) and Anaplastic Lymphoma Kinase (ALK) in the activation of the NLRP3 inflammasome induced by L. monocytogenes infection were investigated. The expression levels of Mst1/2, phospho (p)-ALK, p-JNK, Nek7, and NLRP3 downstream molecules including activated caspase- 1 (p20) and mature interleukin (IL)-1β (p17), were upregulated in L. monocytogenes-infected macrophages. The ALK inhibitor significantly decreased the expression of p-JNK, Nek7, and NLRP3 downstream molecules in macrophages infected with L. monocytogenes. Furthermore, the Mst1/2 inhibitor markedly inhibited the L. monocytogenes-induced activation of ALK, subsequently downregulating the expression of p-JNK, Nek7, and NLRP3 downstream molecules. Therefore, our study demonstrated that Mst1/2-ALK mediated the activation of the NLRP3 inflammasome by promoting the interaction between Nek7 and NLRP3 via JNK during L. monocytogenes infection, which subsequently increased the maturation and release of proinflammatory cytokine to resist pathogen infection. Moreover, Listeriolysin O played a key role in the process. In addition, we also found that the L. monocytogenes-induced apoptosis of J774A.1 cells was reduced by the Mst1/2 or ALK inhibitor. The present study reported, for the first time, that the Mst1/2-ALK-JNK-NLRP3 signaling pathway plays a vital proinflammatory role during L. monocytogenes infection.

Citations

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  • IL-18 biology in severe asthma
    Sarita Thawanaphong, Aswathi Nair, Emily Volfson, Parameswaran Nair, Manali Mukherjee
    Frontiers in Medicine.2024;[Epub]     CrossRef
  • TRAF6-TAK1-IKKβ pathway mediates TLR2 agonists activating “one-step” NLRP3 inflammasome in human monocytes
    Mengdan Chen, Shi Yu, Yuhui Gao, Jiaxun Li, Xun Wang, Bin Wei, Guangxun Meng
    Cytokine.2023; 169: 156302.     CrossRef
  • ALK-JNK signaling promotes NLRP3 inflammasome activation and pyroptosis via NEK7 during Streptococcus pneumoniae infection
    Xia Wang, Yan Zhao, Dan Wang, Chang Liu, Zhi Qi, Huixin Tang, Yashan Liu, Shiqi Zhang, Yali Cui, Yingying Li, Ruiqing Liu, Yanna Shen
    Molecular Immunology.2023; 157: 78.     CrossRef
  • Inflammasome activation by Gram-positive bacteria: Mechanisms of activation and regulation
    A. Marijke Keestra-Gounder, Prescilla Emy Nagao
    Frontiers in Immunology.2023;[Epub]     CrossRef
  • Toxoplasma gondii profilin induces NLRP3 activation and IL-1β production/secretion in THP-1 cells
    Hossein Pazoki, Hamed Mirjalali, Maryam Niyyati, Seyed Javad Seyed Tabaei, Nariman Mosaffa, Shabnam Shahrokh, Hamid Asadzadeh Ahdaei, Andreas Kupz, Mohammad Reza Zali
    Microbial Pathogenesis.2023; 180: 106120.     CrossRef
  • The Critical Role of Potassium Efflux and Nek7 in Pasteurella multocida-Induced NLRP3 Inflammasome Activation
    Yu Wang, Zheng Zeng, Jinrong Ran, Lianci Peng, Xingping Wu, Chao Ye, Chunxia Dong, Yuanyi Peng, Rendong Fang
    Frontiers in Microbiology.2022;[Epub]     CrossRef
  • Coral and it's symbionts responses to the typical global marine pollutant BaP by 4D-Proteomics approach
    Yuebin Pei, Shuai Chen, Yuting Zhang, Volovych Olga, Yuanchao Li, Xiaoping Diao, Hailong Zhou
    Environmental Pollution.2022; 307: 119440.     CrossRef
  • NEK7-Mediated Activation of NLRP3 Inflammasome Is Coordinated by Potassium Efflux/Syk/JNK Signaling During Staphylococcus aureus Infection
    Ruiqing Liu, Yashan Liu, Chang Liu, Aijiao Gao, Lin Wang, Huixin Tang, Qiang Wu, Xia Wang, Derun Tian, Zhi Qi, Yanna Shen
    Frontiers in Immunology.2021;[Epub]     CrossRef
Deep convolutional neural network: a novel approach for the detection of Aspergillus fungi via stereomicroscopy
Haozhong Ma , Jinshan Yang , Xiaolu Chen , Xinyu Jiang , Yimin Su , Shanlei Qiao , Guowei Zhong
J. Microbiol. 2021;59(6):563-572.   Published online March 29, 2021
DOI: https://doi.org/10.1007/s12275-021-1013-z
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AbstractAbstract
Fungi of the genus Aspergillus are ubiquitously distributed in nature, and some cause invasive aspergillosis (IA) infections in immunosuppressed individuals and contamination in agricultural products. Because microscopic observation and molecular detection of Aspergillus species represent the most operator-dependent and time-intensive activities, automated and cost-effective approaches are needed. To address this challenge, a deep convolutional neural network (CNN) was used to investigate the ability to classify various Aspergillus species. Using a dissecting microscopy (DM)/stereomicroscopy platform, colonies on plates were scanned with a 35× objective, generating images of sufficient resolution for classification. A total of 8,995 original colony images from seven Aspergillus species cultured in enrichment medium were gathered and autocut to generate 17,142 image crops as training and test datasets containing the typical representative morphology of conidiophores or colonies of each strain. Encouragingly, the Xception model exhibited a classification accuracy of 99.8% on the training image set. After training, our CNN model achieved a classification accuracy of 99.7% on the test image set. Based on the Xception performance during training and testing, this classification algorithm was further applied to recognize and validate a new set of raw images of these strains, showing a detection accuracy of 98.2%. Thus, our study demonstrated a novel concept for an artificial-intelligence-based and cost-effective detection
method
ology for Aspergillus organisms, which also has the potential to improve the public’s understanding of the fungal kingdom.

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  • Outlier classification for microbiological open set recognition
    Yining Pan, Wei Ye, Dejin Xie, Jiaoyu Wang, Hongkai Wang, Haiping Qiu
    Computers and Electronics in Agriculture.2024; 224: 109104.     CrossRef
  • Harnessing of Artificial Intelligence for the Diagnosis and Prevention of Hospital-Acquired Infections: A Systematic Review
    Buket Baddal, Ferdiye Taner, Dilber Uzun Ozsahin
    Diagnostics.2024; 14(5): 484.     CrossRef
  • Current status and new experimental diagnostic methods of invasive fungal infections after hematopoietic stem cell transplantation
    Zhenhua Tang, HaiTao Wang, Yuankai Liu, Chen Wang, Xinye Li, Qiong Yang
    Archives of Microbiology.2024;[Epub]     CrossRef
  • Artificial Intelligence: Exploring utility in detection and typing of fungus with futuristic application in fungal cytology
    Nidhi Singla, Reetu Kundu, Pranab Dey
    Cytopathology.2024; 35(2): 226.     CrossRef
  • Label-Free Optical Transmission Tomography for Direct Mycological Examination and Monitoring of Intracellular Dynamics
    Eliott Teston, Marc Sautour, Léa Boulnois, Nicolas Augey, Abdellah Dighab, Christophe Guillet, Dea Garcia-Hermoso, Fanny Lanternier, Marie-Elisabeth Bougnoux, Frédéric Dalle, Louise Basmaciyan, Mathieu Blot, Pierre-Emmanuel Charles, Jean-Pierre Quenot, Bi
    Journal of Fungi.2024; 10(11): 741.     CrossRef
  • Artificial Intelligence and Microbiology
    Mert Kandilci, Gülfer Yakıcı, Mediha Begüm Kayar
    Experimental and Applied Medical Science.2024; 5(2): 119.     CrossRef
  • Attention-Guided Transfer Learning for Identification of Filamentous Fungi Encountered in the Clinical Laboratory
    Tsi-Shu Huang, Kevin Wang, Xiu-Yuan Ye, Chii-Shiang Chen, Fu-Chuen Chang, Paschalis Vergidis, Yang Zhang
    Microbiology Spectrum.2023;[Epub]     CrossRef
  • Artificial Intelligence Based Test Systems to Resist Waterborne Diseases by Early and Rapid Identification of Pathogens: A Review
    Chethna Joy, G. Naveen Sundar, D. Narmadha
    SN Computer Science.2023;[Epub]     CrossRef
  • Plant and Animal Species Recognition Based on Dynamic Vision Transformer Architecture
    Hang Pan, Lun Xie, Zhiliang Wang
    Remote Sensing.2022; 14(20): 5242.     CrossRef
  • Machine Learning and Deep Learning Based Computational Approaches in Automatic Microorganisms Image Recognition: Methodologies, Challenges, and Developments
    Priya Rani, Shallu Kotwal, Jatinder Manhas, Vinod Sharma, Sparsh Sharma
    Archives of Computational Methods in Engineering.2022; 29(3): 1801.     CrossRef
  • A Small Sample Recognition Model for Poisonous and Edible Mushrooms based on Graph Convolutional Neural Network
    Li Zhu, Xin Pan, Xinpeng Wang, Fu Haito, Abdul Rehman Javed
    Computational Intelligence and Neuroscience.2022; 2022: 1.     CrossRef
  • Morphologic identification of clinically encountered moulds using a residual neural network
    Ran Jing, Xiang-Long Yin, Xiu-Li Xie, He-Qing Lian, Jin Li, Ge Zhang, Wen-Hang Yang, Tian-Shu Sun, Ying-Chun Xu
    Frontiers in Microbiology.2022;[Epub]     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.

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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
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    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
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  • 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
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    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
Analysis of the L-malate biosynthesis pathway involved in poly(β-L-malic acid) production in Aureobasidium melanogenum GXZ-6 by addition of metabolic intermediates and inhibitors
Wei Zeng , Bin Zhang , Qi Liu , Guiguang Chen , Zhiqun Liang
J. Microbiol. 2019;57(4):281-287.   Published online February 5, 2019
DOI: https://doi.org/10.1007/s12275-019-8424-0
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AbstractAbstract
Poly(β-L-malic acid) (PMA) is a promising polyester formed from L-malate in microbial cells. Malate biosynthesis is crucial for PMA production. Previous studies have shown that the non-oxidative pathway or oxidative pathway (TCA cycle) is the main biosynthetic pathway of malate in most of PMAproducing strains, while the glyoxylate cycle is only a supplementary pathway. In this study, we investigated the effect of exogenous metabolic intermediates and inhibitors of the malate biosynthetic pathway on PMA production by Aureobasidium melanogenum GXZ-6. The results showed that PMA production was stimulated by maleic acid (a fumarase inhibitor) and sodium malonate (a succinate dehydrogenase inhibitor) but inhibited by succinic acid and fumaric acid. This indicated that the TCA cycle might not be the only biosynthetic pathway of malate. In addition, the PMA titer increased by 18.1% upon the addition of glyoxylic acid after 72 h of fermentation, but the PMA titer decreased by 7.5% when itaconic acid (an isocitrate lyase inhibitor) was added, which indicated that malate for PMA production was synthesized significantly via the glyoxylate cycle rather than the TCA cycle. Furthermore, in vitro enzyme activities of the TCA and glyoxylate cycles suggested that the glyoxylate cycle significantly contributed to the PMA production, which is contradictory to what has been reported previously in other PMA-producing A. pullulans.

Citations

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  • De novo transcriptome assembly of Aureobasidium melanogenum CGMCC18996 to analyze the β-poly(L-malic acid) biosynthesis pathway under the CaCO3 addition
    Genan Wang, Haisong Yin, Tingbin Zhao, Donglin Yang, Shiru Jia, Changsheng Qiao
    Food Science and Human Wellness.2023; 12(4): 1248.     CrossRef
  • Microbial L-malic acid production: History, current progress, and perspectives
    Yongyan Xi, Feiyu Fan, Xueli Zhang
    Green Carbon.2023; 1(2): 118.     CrossRef
  • Evaluation of enhancing effect of soybean oil on polymalic acid production by Aureobasidium pullulans HA-4D
    Jun Xia, Sili Liu, Jiali Jiao, Zhongyang Qiu, Xiaoyang Liu, Aiyong He, Ning Xu, Jiaxing Xu
    Bioprocess and Biosystems Engineering.2022; 45(10): 1673.     CrossRef
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    Byeong Seob Oh, Won Jung Choi, Ji-Sun Kim, Seoung Woo Ryu, Seung Yeob Yu, Jung-Sook Lee, Seung-Hwan Park, Se Won Kang, Jiyoung Lee, Won Yong Jung, Young-Min Kim, Jae-Ho Jeong, Ju Huck Lee
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  • Small-Sized Co-Polymers for Targeted Delivery of Multiple Imaging and Therapeutic Agents
    Julia Y. Ljubimova, Arshia Ramesh, Liron L. Israel, Eggehard Holler
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Metabolomic profiling reveals enrichment of cordycepin in senescence process of Cordyceps militaris fruit bodies
Junsang Oh , Deok-Hyo Yoon , Bhushan Shrestha , Hyung-Kyoon Choi , Gi-Ho Sung
J. Microbiol. 2019;57(1):54-63.   Published online December 29, 2018
DOI: https://doi.org/10.1007/s12275-019-8486-z
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AbstractAbstract
Cordyceps militaris is a species of Cordyceps that is classified in the Cordycipitaceae family and is well known in East Asia as a traditional medicinal mushroom. Its artificial fruit body has been widely cultivated for commercial use in cosmetics, functional food, and medicine. To explore the metabolites associated with fruit body development, we conducted gas chromatography mass spectrometry (GC-MS) analyses based on developmental stage, which was divided into the growth period (stage 1, stage 2, and stage 3) and aging period (stage 4). We detected 39 biochemical metabolites associated with nucleotide, carbohydrate, and amino acid metabolism. Cordycepin, one of the representative bioactive compounds in C. militaris, was significantly enriched in stage 4 of aging period and is associated with glucose accumulation. The accumulation of cordycepin in stage 4 of aging period also seems to be related to the glutamine and glutamic acid pathway. Our
results
also showed enrichment of other bioactive compounds such as mannitol and xylitol in stage 4 of aging period. Our metabolomic profiling based on the developmental stages of C. militaris is useful for exploring bioactive compounds (e.g., cordycepin, mannitol, GABA, and xylitol) that are enriched in stage 4 of aging period and understanding the biosynthetic mechanisms associated with cordycepin production. Through optimization of fruit body cultivation by selecting stage 4 of aging period as a harvesting time, our findings can be utilized in food and medical applications of C. militaris in future.

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Cot kinase plays a critical role in Helicobacter pylori-induced IL-8 expression
Sungil Jang , Jinmoon Kim , Jeong-Heon Cha
J. Microbiol. 2017;55(4):311-317.   Published online March 31, 2017
DOI: https://doi.org/10.1007/s12275-017-7052-9
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AbstractAbstract
Helicobacter pylori is a major pathogen causing various gastric diseases including gastric cancer. Infection of H. pylori induces pro-inflammatory cytokine IL-8 expression in gastric epithelial cells in the initial inflammatory process. It has been known that H. pylori can modulate Ras-Raf-Mek-Erk signal pathway for IL-8 induction. Recently, it has been shown that another signal molecule, cancer Osaka thyroid oncogene/tumor progression locus 2 (Cot/Tpl2) kinase, activates Mek and Erk and plays a role in the Erk pathway, similar to MAP3K signal molecule Raf kinase. Therefore, the objective of this study was to determine whether Cot kinase might be involved in IL-8 induction caused by H. pylori infection. AGS gastric epithelial cells were infected by H. pylori strain G27 or its isogenic mutants lacking cagA or type IV secretion system followed by treatment with Cot kinase inhibitor (KI) or siRNA specific for Cot kinase. Activation of Erk was assessed by Western blot analysis and expression of IL-8 was measured by ELISA. Treatment with Cot KI reduced both transient and sustained Erk activation. It also reduced early and late IL-8 secretion in the gastric epithelial cell line. Furthermore, siRNA knockdown of Cot inhibited early and late IL-8 secretion induced by H. pylori infection. Taken together, these results suggest that Cot kinase might play a critical role in H. pylori type IV secretion apparatus-dependent early IL-8 secretion and CagA-dependent late IL-8 secretion as an alternative signaling molecule in the Erk pathway.

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  • Helicobacter pylori infection is correlated with the incidence of erosive oral lichen planus and the alteration of the oral microbiome composition
    Shutong Li, Yangheng Zhang, Zongcheng Yang, Jingyuan Li, Ya Li, Huanjie Li, Wenjuan Li, Jihui Jia, Shaohua Ge, Yundong Sun
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    Keshan Zhang, Minghao Yan, Junhong Hao, Chaochao Shen, Zixiang Zhu, Dajun Zhang, Jing Hou, Guowei Xu, Dan Li, Haixue Zheng, Xiangtao Liu, Susana López
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Metagenomic analysis reveals the contribution of anaerobic methanotroph-1b in the oxidation of methane at the Ulleung Basin, East Sea of Korea
Jin-Woo Lee , Kae Kyoung Kwon , Jang-Jun Bahk , Dong-Hun Lee , Hyun Sook Lee , Sung Gyun Kang , Jung-Hyun Lee
J. Microbiol. 2016;54(12):814-822.   Published online November 26, 2016
DOI: https://doi.org/10.1007/s12275-016-6379-y
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AbstractAbstract
We have previously identified a sulfate methane transition zone (SMTZ) within the methane hydrate-bearing sediment in the Ulleung Basin, East Sea of Korea, and the presence of ANME-1b group in the sediment has been shown by phylogenetic analysis of a 16S rRNA gene. Herein, we describe taxonomic and functional profiling in the SMTZ sample by metagenomic analysis, comparing with that of surface sediment. Metagenomic sequences of 115 Mbp and 252 Mbp were obtained from SMTZ and surface sediments, respectively. The taxonomic profiling using BLASTX against the SEED within MG-RAST showed the prevalence of methanogens (19.1%), such as Methanosarcinales (12.0%) and Methanomicrobiales (4.1%) predominated within the SMTZ metagenome. A number of 185,200 SMTZ reads (38.9%) and 438,484 surface reads (62.5%) were assigned to functional categories, and methanogenesis-related reads were statistically significantly overrepresented in the SMTZ metagenome. However, the mapping analysis of metagenome reads to the reference genomes, most of the sequences of the SMTZ metagenome were mapped to ANME-1 draft genomes, rather than those of methanogens. Furthermore, the two copies of the methyl-coenzyme M reductase gene (mcrA) segments of the SMTZ metagenome were clustered with ANME-1b in the phylogenetic cluster. These results indicate that ANME- 1b reads were miss-annotated to methanogens due to limitation of database. Many of key genes necessary for reverse methanogenesis were present in the SMTZ metagenome, except for N5,N10-methenyl-H4MPT reductase (mer) and CoBCoM heterodisulfide reductase subunits D and E (hdrDE). These data suggest that the ANME-1b represents the primary player the anaerobic methane oxidation in the SMTZ, of the methane hydrate-bearing sediment at the Ulleung Basin, East Sea of Korea.

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    Youzhi Xin, Nengyou Wu, Zhilei Sun, Hongmei Wang, Ye Chen, Cuiling Xu, Wei Geng, Hong Cao, Xilin Zhang, Bin Zhai, Dawei Yan
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Research Support, Non-U.S. Gov'ts
In silico analysis and experimental validation of lipoprotein and novel Tat signal peptides processing in Anabaena sp. PCC7120
Sonika Kumari , Akhilesh Kumar Chaurasia
J. Microbiol. 2015;53(12):837-846.   Published online December 2, 2015
DOI: https://doi.org/10.1007/s12275-015-5281-3
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AbstractAbstract
Signal peptide (SP) plays a pivotal role in protein translocation. Lipoprotein- and twin arginine translocase (Tat) dependent signal peptides were studied in All3087, a homolog of competence protein of Synechocystis PCC6803 and in two putative alkaline phosphatases (ALPs, Alr2234 and Alr4976), respectively. In silico analysis of All3087 is shown to possess the characteristics feature of competence proteins such as helix-hairpin-helix, N and C-terminal HKD endonuclease domain, calcium binding domain and N-terminal lipoprotein signal peptide. The SP recognition-cleavage site in All3087 was predicted (AIA-AC) using SignalP while further in-depth analysis using Pred-Lipo and WebLogo analysis for consensus sequence showed it as IAA-C. Activities of putative ALPs were confirmed by heterologous overexpression, activity assessment and zymogram analysis. ALP activity in Anabaena remains cell bound in log-phase, but during late log/stationary phase, an enhanced ALP activity was detected in extracellular milieu. The enhancement of ALP activity during stationary phase was not only due to inorganic phosphate limitation but also contributed by the presence of novel bipartite Tat-SP. The Tat signal transported the folded active ALPs to the membrane, followed by anchoring into the membrane and successive cleavage enabling transportation of the ALPs to the extracellular milieu, because of bipartite architecture and processing of transit Tat-SP.

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    Y. Wang, M.J.O. Wakelam, V.A. Bankaitis, M.I. McDermott
    Advances in Biological Regulation.2024; 91: 101000.     CrossRef
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Relationships between the use of Embden Meyerhof pathway (EMP) or Phosphoketolase pathway (PKP) and lactate production capabilities of diverse Lactobacillus reuteri strains
Grégoire Burgé , Claire Saulou-Bérion , Marwen Moussa , Florent Allais , Violaine Athes , Henry-Eric Spinnler
J. Microbiol. 2015;53(10):702-710.   Published online October 2, 2015
DOI: https://doi.org/10.1007/s12275-015-5056-x
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AbstractAbstract
The aims of this study is to compare the growth and glucose metabolism of three Lactobacillus reuteri strains (i.e. DSM 20016, DSM 17938, and ATCC 53608) which are lactic acid bacteria of interest used for diverse applications such as probiotics implying the production of biomass, or for the production of valuable chemicals (3-hydroxypropionaldehyde, 3-hydroxypropionic acid, 1,3-propanediol). However, the physiological diversity inside the species, even for basic metabolisms, like its capacity of acidification or glucose metabolism, has not been studied yet. In the present work, the growth and metabolism of three strains representative of the species diversity have been studied in batch mode. The strains were compared through characterization of growth kinetics and evaluation of acidification kinetics, substrate consumption and product formation. The results showed significant differences between the three strains which may be explained, at least in part, by variations in the distribution of carbon source between two glycolytic pathways during the bacterial growth: the phosphoketolase or heterolactic pathway (PKP) and the Embden-Meyerhof pathway (EMP). It was also shown that, in the context of obtaining a large amount of biomass, DSM 20016 and DSM 17938 strains were the most effective in terms of growth kinetics. The DSM 17938 strain, which shows the more significant metabolic shift from EMP to PKP when the pH decreases, is more effective for lactate production.

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