Journal of Microbiology

Journal Articles

Vaginal Microbiome Dysbiosis is Associated with the Different Cervical Disease Status: Yingying Ma , Yanpeng Li , Yanmei Liu , Le Cao , Xiao Han , Shujun Gao , Chiyu Zhang; J. Microbiol. 2023;61(4):423-432. Published online April 3, 2023; DOI: https://doi.org/10.1007/s12275-023-00039-3

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Vaginal microbiome composition was demonstrated to be associated with cervical disease. The colonization characteristics of vaginal microbes and their association with the different cervical disease status, especially cervical cancer (CC), are rarely investigated. In this cross-sectional study, we characterized the vaginal microbiome of women with different status of cervical diseases, including 22 NV + (normal tissue with HPV infection), low-grade squamous intraepithelial lesion (LSIL, n = 45), high-grade squamous intraepithelial lesion (HSIL, n = 36) and CC (n = 27) using bacterial 16S DNA sequencing. Thirty HPV-negative women with normal tissue were used as the control group. We found that higher diversity of microbiome with gradual depletion of Lactobacillus, especially L. crispatus, was associated with the severity of cervical disease. High-risk HPV16 infection was associated with higher microbiome diversity and depletion of Lactobacillus in high-grade cervical diseases (i.e. HSIL and CC). The CC group was characterized by higher levels of Fannyhessea vaginae, Prevotella, Bacteroides, Finegoldia, Vibrio, Veillonella, Peptostreptococcus, and Dialister. Co-occurrence network analyses showed that negative correlations were exclusively observed between Lactobacillus and other bacteria, and almost all non-Lactobacillus bacteria were positively correlated with each other. In particular, the most diverse and complex co-occurrence network of vaginal bacteria, as well as a complete loss of L. crispatus, was observed in women with CC. Logistic regression model identified HPV16 and Lactobacillus as significant risk and protective factors for CC, respectively. These results suggest that specific Lactobacillus species (e.g. L. crispatus and L. iners) can be used as important markers to target prevention measures prioritizing HPV16-infected women and other hrHPV-infected women for test, vaccination and treat initiatives.

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Vaginal Microbiome and Pregnancy Complications: A Review
Angeliki Gerede, Konstantinos Nikolettos, Eleftherios Vavoulidis, Chrysoula Margioula-Siarkou, Stamatios Petousis, Maria Giourga, Panagiotis Fotinopoulos, Maria Salagianni, Sofoklis Stavros, Konstantinos Dinas, Nikolaos Nikolettos, Ekaterini Domali
Journal of Clinical Medicine.2024; 13(13): 3875. CrossRef
Advancements in the Vaginal Microenvironment and Regression of High-Risk Human Papillomavirus
Na He, Cunjian Yi, Qingsong Zeng, Wumei Jing, Wenrong He
Indian Journal of Microbiology.2024;[Epub] CrossRef
Research Progress on Related Factors of Cervical High-Grade Squamous Intraepithelial Lesions
红颖王
Advances in Clinical Medicine.2023; 13(12): 20536. CrossRef
Role of the vaginal microbiome in miscarriage: exploring the relationship
Marwa Saadaoui, Parul Singh, Osman Ortashi, Souhaila Al Khodor
Frontiers in Cellular and Infection Microbiology.2023;[Epub] CrossRef

Gamma-glutamyltransferase of Helicobacter pylori alters the proliferation, migration, and pluripotency of mesenchymal stem cells by affecting metabolism and methylation status: Zeyu Wang , Weijun Wang , Huiying Shi , Lingjun Meng , Xin Jiang , Suya Pang , Mengke Fan , Rong Lin; J. Microbiol. 2022;60(6):627-639. Published online April 18, 2022; DOI: https://doi.org/10.1007/s12275-022-1575-4

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Abstract

Virulence factor gamma-glutamyltransferase (GGT) of H. pylori consumes glutamine (Gln) in the stomach to decrease the tricarboxylic acid metabolite alpha-ketoglutarate (α-kg) and alter the downstream regulation of α-kg as well as cellular biological characteristics. Our previous research indicated that under H. pylori infection, mesenchymal stem cells (MSCs) migrated to the stomach and participated in gastric cancer (GC) development either by differentiating into epithelial cells or promoting angiogenesis. However, how MSCs themselves participate in H. pylori-indicated GC remains unclear. Therefore, a GGT knockout H. pylori strain (Hp- KS-1) was constructed, and downstream histone H3K9 and H3K27 methylation and the PI3K/AKT signaling pathway of α-kg were detected using Western blotting. The biological characteristics of MSCs were also examined. An additive α-kg supplement was also added to H. pylori-treated MSCs to investigate alterations in these aspects. Compared to the control and Hp-KS-1 groups, H. pylori-treated MSCs reduced Gln and α-kg, increased H3K9me3 and H3K27me3, activated the PI3K-AKT signaling pathway, and promoted the proliferation, migration, self-renewal, and pluripotency of MSCs. The addition of α-kg rescued the H. pylori-induced alterations. Injection of MSCs to nude mice resulted in the largest tumors in the H. pylori group and significantly reduced tumor sizes in the Hp-KS-1 and α-kg groups. In summary, GGT of H. pylori affected MSCs by interfering with the metabolite α-kg to increase trimethylation of histone H3K9 and H3K27, activating the PI3K/AKT signaling pathway, and promoting proliferation, migration, self-renewal, and pluripotency in tumorigenesis, elucidating the mechanisms of MSCs in GC development.

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Gamma-glutamyl transferase secreted by Helicobacter pylori promotes the development of gastric cancer by affecting the energy metabolism and histone methylation status of gastric epithelial cells
Xin Jiang, Weijun Wang, Zeyu Wang, Zhe Wang, Huiying Shi, Lingjun Meng, Suya Pang, Mengke Fan, Rong Lin
Cell Communication and Signaling.2024;[Epub] CrossRef
Design of a Helicobacter pylori multi-epitope vaccine based on immunoinformatics
Man Cui, Xiaohui Ji, Fengtao Guan, Guimin Su, Lin Du
Frontiers in Immunology.2024;[Epub] CrossRef
Gastric cancer and mesenchymal stem cell-derived exosomes: from pro-tumorigenic effects to anti-cancer vehicles
Maryam Dolatshahi, Ahmad Reza Bahrami, Qaiser Iftikhar Sheikh, Mohsen Ghanbari, Maryam M. Matin
Archives of Pharmacal Research.2024; 47(1): 1. CrossRef
Mesenchymal Stem Cell-Derived Exosomes Modulate Angiogenesis in Gastric Cancer
Fawzy Akad, Veronica Mocanu, Sorin Nicolae Peiu, Viorel Scripcariu, Bogdan Filip, Daniel Timofte, Florin Zugun-Eloae, Magdalena Cuciureanu, Monica Hancianu, Teodor Oboroceanu, Laura Condur, Radu Florin Popa
Biomedicines.2023; 11(4): 1031. CrossRef
Helicobacter pylori and Its Role in Gastric Cancer
Victor E. Reyes
Microorganisms.2023; 11(5): 1312. CrossRef

Retracted Publication

Cryptic prophages in a blaNDM-1-bearing plasmid increase bacterial survival against high NaCl concentration, high and low temperatures, and oxidative and immunological stressors: So Yeon Kim , Kwan Soo Ko; J. Microbiol. 2020;58(6):483-488. Published online March 28, 2020; DOI: https://doi.org/10.1007/s12275-020-9605-6

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Abstract

In this study, we investigated the effect of cryptic prophage regions in a blaNDM-1-bearing plasmid, which was identified in a patient from South Korea, on the survival of bacteria against adverse environmental conditions. First, we conjugated the intact plasmid and plasmids with deleted cryptic prophages into Escherichia coli DH5α. The E. coli transconjugants carrying the plasmid with intact cryptic prophages showed increased survival during treatment with a high concentration of NaCl, high and low temperatures, an oxidative stressor (H2O2), and an immunological stressor (human serum). By contrast, the transconjugants carrying the plasmid with a single-cryptic prophage knockout did not show any change in survival rates. mRNA expression analyses revealed that the genes encoding sigma factor proteins were highly upregulated by the tested stressors and affected the expression of various proteins (antioxidant, cell osmosis-related, heat shock, cold shock, and universal stress proteins) associated with the specific defense against each stress. These findings indicate that a bacterial strain carrying a plasmid with intact carbapenemase gene and cryptic prophage regions exhibited an increased resistance against simulated environmental stresses, and cryptic prophages in the plasmid might contribute to this enhanced stress resistance. Our study indicated that the coselection of antibiotic resistance and resistance to other stresses may help bacteria to increase survival rates against adverse environments and disseminate.

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Uncovering the virome and its interaction with antibiotic resistome during compost fertilization
Qingxia Zhang, Lei Zhou, Yilong Zhao, Shuhong Gao, Yanjun Yang, Qingyun Chen, Wenhui Li, Qi Qi, Qiang Dong, Jiesi Lei, Xue Guo, Qun Gao, Yunfeng Yang
Journal of Hazardous Materials.2023; 457: 131763. CrossRef
Regulator of RNase E activity modulates the pathogenicity of Salmonella Typhimurium
Jaejin Lee, Eunkyoung Shin, Ji-Hyun Yeom, Jaeyoung Park, Sunwoo Kim, Minho Lee, Kangseok Lee
Microbial Pathogenesis.2022; 165: 105460. CrossRef
Presence and Persistence of Putative Lytic and Temperate Bacteriophages in Vaginal Metagenomes from South African Adolescents
Anna-Ursula Happel, Christina Balle, Brandon S. Maust, Iyaloo N. Konstantinus, Katherine Gill, Linda-Gail Bekker, Rémy Froissart, Jo-Ann Passmore, Ulas Karaoz, Arvind Varsani, Heather Jaspan
Viruses.2021; 13(12): 2341. CrossRef
Regulator of ribonuclease activity modulates the pathogenicity of Vibrio vulnificus
Jaejin Lee, Eunkyoung Shin, Jaeyeong Park, Minho Lee, Kangseok Lee
Journal of Microbiology.2021; 59(12): 1133. CrossRef

Research Support, Non-U.S. Gov'ts

Genipin as a novel chemical activator of EBV lytic cycle: Myoungki Son , Minjung Lee , Eunhyun Ryu , Aree Moon , Choon-Sik Jeong , Yong Woo Jung , Gyu Hwan Park , Gi-Ho Sung , Hyosun Cho , Hyojeung Kang; J. Microbiol. 2015;53(2):155-165. Published online January 28, 2015; DOI: https://doi.org/10.1007/s12275-015-4672-9

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Abstract

Epstein-Barr virus (EBV) is a ubiquitous gammaherpesvirus that causes acute infection and establishes life-long latency. EBV causes several human cancers, including Burkitt's lymphoma, nasopharyngeal and gastric carcinoma. Antiviral agents can be categorized as virucides, antiviral chemotherapeutic agents, and immunomodulators. Most antiviral agents affect actively replicating viruses, but not their latent forms. Novel antiviral agents must be active on both the replicating and the latent forms of the virus. Gardenia jasminoides is an evergreen flowering plant belonging to the Rubiaceae family and is most commonly found growing wild in Vietnam, Southern China, Taiwan, Japan, Myanmar, and India. Genipin is an aglycone derived from an iridoid glycoside called geniposide, which is present in large quantities in the fruit of G. jasminoides. In this study, genipin was evaluated for its role as an antitumor and antiviral agent that produces inhibitory effects against EBV and EBV associated gastric carcinoma (EBVaGC). In SNU719 cells, one of EBVaGCs, genipin caused significant cytotoxicity (70 μM), induced methylation on EBV C promoter and tumor suppressor gene BCL7A, arrested cell-cycle progress (S phases), upregulated EBV latent/lytic genes in a dose-dependent manner, stimulated EBV progeny production, activated EBV F promoter for EBV lytic activation, and suppressed EBV infection. These
results
indicated that genipin could be a promising candidate for antiviral and antitumor agents against EBV and EBVaGC.

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Research Progress of EB Virus-Associated Gastric Cancer
婷婷宋
Advances in Clinical Medicine.2024; 14(08): 862. CrossRef
Genipin’s potential as an anti-cancer agent: from phytochemical origins to clinical prospects
Lapava Natallia, Aida Dama, Era Gorica, Karaliova Darya, Sheila I. Peña-Corona, Hernán Cortés, Antonello Santini, Dietrich Büsselberg, Gerardo Leyva-Gómez, Javad Sharifi-Rad
Medical Oncology.2024;[Epub] CrossRef
Update of Natural Products and Their Derivatives Targeting Epstein–Barr Infection
Rosamaria Pennisi, Paola Trischitta, Marianna Costa, Assunta Venuti, Maria Pia Tamburello, Maria Teresa Sciortino
Viruses.2024; 16(1): 124. CrossRef
Genipin-Crosslinking Effects on Biomatrix Development for Cutaneous Wound Healing: A Concise Review
Dewi Utami Nike, Nur Izzah Md Fadilah, Nusaibah Sallehuddin, Ahmad Yasser Hamdi Nor Azlan, Farrah Hani Imran, Manira Maarof, Mh Busra Fauzi
Frontiers in Bioengineering and Biotechnology.2022;[Epub] CrossRef
Genipin, an Inhibitor of UCP2 as a Promising New Anticancer Agent: A Review of the Literature
Young Seok Cho
International Journal of Molecular Sciences.2022; 23(10): 5637. CrossRef
Preparation, characterization, and in vitro release kinetics of doxorubicin-loaded magnetosomes
Shuang Zhang, Xinxin Fan, Guojing Zhang, Weidong Wang, Lei Yan
Journal of Biomaterials Applications.2022; 36(8): 1469. CrossRef
An Integrated Analysis Reveals Geniposide Extracted From Gardenia jasminoides J.Ellis Regulates Calcium Signaling Pathway Essential for Influenza A Virus Replication
Lirun Zhou, Lei Bao, Yaxin Wang, Mengping Chen, Yingying Zhang, Zihan Geng, Ronghua Zhao, Jing Sun, Yanyan Bao, Yujing Shi, Rongmei Yao, Shanshan Guo, Xiaolan Cui
Frontiers in Pharmacology.2021;[Epub] CrossRef
Synthesis of [3H] and [14C]genipin
Adele.E. Queen, David Hesk, David.M. Lindsay, William.J. Kerr, Kenneth Rehder, Tim Fennell, Wayne Mascarella, Desong Zhong, Scott Runyon
Journal of Labelled Compounds and Radiopharmaceuticals.2020; 63(4): 196. CrossRef
Genipin inhibits rotavirus-induced diarrhea by suppressing viral replication and regulating inflammatory responses
Jong-Hwa Kim, Kiyoung Kim, Wonyong Kim
Scientific Reports.2020;[Epub] CrossRef
Genipap (Genipa americana L.) juice intake biomarkers after medium-term consumption
Livia Dickson, Mathieu Tenon, Ljubica Svilar, Pascale Fança-Berthon, Jean-Charles Martin, Hervé Rogez, Fabrice Vaillant
Food Research International.2020; 137: 109375. CrossRef
Evaluation on the antiviral activity of genipin against white spot syndrome virus in crayfish
Ai-Guo Huang, Xiao-Ping Tan, Shen-Ye Qu, Gao-Xue Wang, Bin Zhu
Fish & Shellfish Immunology.2019; 93: 380. CrossRef
Comparative investigation on metabolite changes in ‘wu mi’ production by Vaccinium bracteatum Thunb. leaves based on multivariate data analysis using UPLC–QToF–MS
Mingcong Fan, Yihui Fan, Zhiming Rao, Yan Li, Haifeng Qian, Hui Zhang, Gangcheng Wu, Xiguang Qi, Li Wang
Food Chemistry.2019; 286: 146. CrossRef
Selective oncolytic effect in Epstein-Barr virus (EBV)-associated gastric carcinoma through efficient lytic induction by Euphorbia extracts
Dong-eun Kim, Sunhee Jung, Hyung Won Ryu, Miri Choi, Mingu Kang, Hyunju Kang, Heung Joo Yuk, Hyejeong Jeong, Jiyeon Baek, Jae-Hyoung Song, Janghwan Kim, Hyojeung Kang, Sang-Bae Han, Sei-Ryang Oh, Sungchan Cho
Journal of Functional Foods.2018; 42: 146. CrossRef
Curcuminoids as EBV Lytic Activators for Adjuvant Treatment in EBV-Positive Carcinomas
Octavia Ramayanti, Mitch Brinkkemper, Sandra Verkuijlen, Leni Ritmaleni, Mei Go, Jaap Middeldorp
Cancers.2018; 10(4): 89. CrossRef
EBV transformation induces overexpression of hMSH2/3/6 on B lymphocytes and enhances γδT‐cell‐mediated cytotoxicity via TCR and NKG2D
Yu‐mei Dai, Hai‐ying Liu, Yun‐feng Liu, Yuan Zhang, Wei He
Immunology.2018; 154(4): 673. CrossRef
Infection‐associated epigenetic alterations in gastric cancer: New insight in cancer therapy
Sadegh Fattahi, Mohadeseh Kosari‐Monfared, Elham Ghadami, Monireh Golpour, Parastoo Khodadadi, Mohammad Ghasemiyan, Haleh Akhavan‐Niaki
Journal of Cellular Physiology.2018; 233(12): 9261. CrossRef
Plant-Derived Anticancer Agents: Lessons from the Pharmacology of Geniposide and Its Aglycone, Genipin
Solomon Habtemariam, Giovanni Lentini
Biomedicines.2018; 6(2): 39. CrossRef
Main Human Urinary Metabolites after Genipap (Genipa americana L.) Juice Intake
Livia Dickson, Mathieu Tenon, Ljubica Svilar, Pascale Fança-Berthon, Raphael Lugan, Jean-Charles Martin, Fabrice Vaillant, Hervé Rogez
Nutrients.2018; 10(9): 1155. CrossRef
Genipin: A natural blue pigment for food and health purposes
Iramaia Angélica Neri-Numa, Marina Gabriel Pessoa, Bruno Nicolau Paulino, Glaucia Maria Pastore
Trends in Food Science & Technology.2017; 67: 271. CrossRef
Geniposide and geniposidic acid, modified forms of genipin, attenuate genipin-induced mitochondrial apoptosis without altering the anti-inflammatory ability in KGN cell line
Tao Zuo, Wenming Xu, Henli Li, Hang Song, Minghui Zhu
Medicinal Chemistry Research.2017; 26(2): 499. CrossRef
Primary lymphocyte infection models for KSHV and its putative tumorigenesis mechanisms in B cell lymphomas
Sangmin Kang, Jinjong Myoung
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Lei Bao, Jialin Yu, Haiying Zhong, Daochao Huang, Qi Lu
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Hu Zhang, Ning Feng, Yan‐Tong Xu, Tian‐Xiang Li, Xiu‐Mei Gao, Yan Zhu, Yun Seon Song, Ya‐Nan Wang, Hong‐Hua Wu
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The Suppressive Effects of Geniposide and Genipin on Helicobacter pylori Infections In Vitro and In Vivo
Chiung‐Hung Chang, Jin‐Bin Wu, Jai‐Sing Yang, Yen‐Ju Lai, Chiu‐Hsian Su, Chi‐Cheng Lu, Yuan‐Man Hsu
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Yu Su Shin, Miyeon Cho, Gyu Hwan Park, Hyosun Cho, Hyojeung Kang
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Genipin Enhances Kaposi’s Sarcoma-Associated Herpesvirus Genome Maintenance
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Hypermethylation of the interferon regulatory factor 5 promoter in Epstein-Barr virus-associated gastric carcinoma: Seung Myung Dong , Hyun Gyu Lee , Sung-Gyu Cho , Seung-Hyun Kwon , Heejei Yoon , Hyun-Jin Kwon , Ji Hae Lee , Hyemi Kim , Pil-Gu Park , Hoguen Kim , S. Diane Hayward , Jeon Han Park , Jae Myun Lee; J. Microbiol. 2015;53(1):70-76. Published online January 4, 2015; DOI: https://doi.org/10.1007/s12275-014-4654-3

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Abstract

Interferon regulatory factor-5 (IRF-5), a member of the mammalian IRF transcription factor family, is regulated by p53, type I interferon and virus infection. IRF-5 participates in virus-induced TLR-mediated innate immune responses and may play a role as a tumor suppressor. It was suppressed in various EBV-infected transformed cells, thus it is valuable to identify the suppression mechanism. We focused on a promoter CpG islands methylation, a kind of epigenetic regulation in EBV-associated Burkitt’s lymphomas (BLs) and gastric carcinomas. IRF-5 is not detected in most of EBV-infected BL cell lines due to hypermethylation of IRF-5 distal promoter (promoter-A), which was restored by a demethylating agent, 5-aza-2􍿁-deoxycytidine. Hypomethylation of CpG islands in promoter-A was observed only in EBV type III latent infected BL cell lines (LCL and Mutu III). Similarly, during EBV infection to Akata-4E3 cells, IRF-5 was observed at early time periods (2 days to 8 weeks), concomitant unmethylation of promoter-A, but suppressed in later infection periods as observed in latency I BL cell lines. Moreover, hypermethylation in IRF-5 promoter-A region was also observed in EBV-associated gastric carcinoma (EBVaGC) cell lines or primary gastric carcinoma tissues, which show type I latent infection. In summary, IRF-5 is suppressed by hypermethylation of its promoter-A in most of EBV-infected transformed cells, especially BLs and EBVaGC. EBV-induced carcinogenesis takes an advantage of proliferative effects of TLR signaling, while limiting IRF-5 mediated negative effects in the establishment of EBVaGCs.

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Prediction of Bacterial Proteins Carrying A Nuclear Localization Signal and Nuclear Targeting of HsdM from Klebsiella pneumoniae: Je Chul Lee , Dong Sun Kim , Dong Chan Moon , Jung-Hwa Lee , Mi Jin Kim , Su Man Lee , Yong Seok Lee , Se-Won Kang , Eun Jung Lee , Sang Sun Kang , Eunpyo Lee , Sung Hee Hyun; J. Microbiol. 2009;47(5):641-645. Published online October 24, 2009; DOI: https://doi.org/10.1007/s12275-009-0217-4

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Abstract: Nuclear targeting of bacterial proteins is an emerging pathogenic mechanism whereby bacterial proteins can interact with nuclear molecules and alter the physiology of host cells. The fully sequenced bacterial genome can predict proteins that target the nuclei of host cells based on the presence of nuclear localization signal (NLS). In the present study, we predicted bacterial proteins with the NLS sequences from Klebsiella pneumoniae by bioinformatic analysis, and 13 proteins were identified as carrying putative NLS sequences. Among them, HsdM, a subunit of KpnAI that is a type I restriction-modification system found in K. pneumoniae, was selected for the experimental proof of nuclear targeting in host cells. HsdM carried the NLS sequences, 7KKAKAKK13, in the N-terminus. A transient expression of HsdM-EGFP in COS-1 cells exhibited exclusively a nuclear localization of the fusion proteins, whereas the fusion proteins of HsdM with substitutions in residues lysine to alanine in the NLS sequences, 7AAAKAAA13, were localized in the cytoplasm. HsdM was co-localized with importin α in the nuclei of host cells. Recombinant HsdM alone methylated the eukaryotic DNA in vitro assay. Although HsdM tested in this study has not been considered to be a virulence factor, the prediction of NLS motifs from the full sequenced genome of bacteria extends our knowledge of functional genomics to understand subcellular targeting of bacterial proteins.

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