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- Extracellular vesicles derived from Lactobacillus plantarum restore chemosensitivity through the PDK2-mediated glucose metabolic pathway in 5-FU-resistant colorectal cancer cells
- JaeJin An , Eun-Mi Ha
- J. Microbiol. 2022;60(7):735-745. Published online July 4, 2022
- DOI: https://doi.org/10.1007/s12275-022-2201-1
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- 20 Web of Science
- 16 Crossref
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Abstract
- Metabolic abnormalities are one of the main hallmarks of cancer and are associated with chemoresistance. Therefore, targeting the metabolic reprogramming of cancer cells has the potential to overcome chemoresistance. Probiotic-derived extracellular vesicles (EVs) play important roles in biological function and intracellular communication. However, the inhibitory effect of Lactobacillus plantarum-derived EVs (LpEVs) on colorectal cancer (CRC) cells has not yet been elucidated. This study clearly revealed that increased glycolysis in 5-fluorouracil (5-FU)-resistant CRC cells (CRC/5FUR) is directly related to chemoresistance and that the metabolic shift reversed by LpEVs inhibits cancer cell proliferation and eventually leads to apoptosis. Pyruvate dehydrogenase kinase 2 (PDK2), one of the crucial enzymes for enhancing glycolysis, was upregulated in CRC/5FUR cells. In our study, LpEVs sensitized CRC/5FUR cells to 5-FU by attenuating PDK2 expression in p53-p21-dependent metabolic signaling, thereby circumventing 5-FU resistance. We demonstrated the effect of cellular responses to 5-FU by modifying the PDK2 expression level in both 5-FU-sensitive parental CRC and 5- FU resistant CRC cell lines. Finally, we revealed that the PDK2 signaling pathway can potentially be targeted using LpEVs treatment to overcome chemoresistant CRC, thereby providing a potential strategy for CRC treatment by intervening in tumor metabolism.
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Citations
Citations to this article as recorded by
- Effect of probiotic extracellular vesicles and their applications on health and disease
Guangzhao Wang, Yang Wang, Kangliang Sheng, Yongzhong Wang
Journal of the Science of Food and Agriculture.2025;[Epub] CrossRef - Incorporation of recombinant proteins into extracellular vesicles by Lactococcus cremoris
Tina Vida Plavec, Kristina Žagar Soderžnik, Giulia Della Pelle, Špela Zupančič, Robert Vidmar, Aleš Berlec
Scientific Reports.2025;[Epub] CrossRef - The benefits of Lactiplantibacillus plantarum: From immunomodulator to vaccine vector
Joshua Tobias, Stefan Heinl, Kristina Dendinovic, Ajša Ramić, Anna Schmid, Catherine Daniel, Ursula Wiedermann
Immunology Letters.2025; 272: 106971. CrossRef - Interconnections within the tumor microenvironment: extracellular vesicles as critical players of metabolic reprogramming in tumor cells
Carol Costa Encarnação, Giselle Marianne Faria, Victor Aguiar Franco, Luiz Gabriel Xavier Botelho, João Alfredo Moraes, Mariana Renovato-Martins
Journal of Cancer Metastasis and Treatment.2024;[Epub] CrossRef - Review of METTL3 in colorectal cancer: From mechanisms to the therapeutic potential
Lexuan Zhang, Zhenwei Mao, Kai Yin, Shengjun Wang
International Journal of Biological Macromolecules.2024; 277: 134212. CrossRef -
Extracellular Vesicles from
Lacticaseibacillus Paracasei
PC-H1 Inhibit HIF-1α-Mediated Glycolysis of Colon Cancer
Yangqian Shi, Chunliang Zhang, Wanyu Cao, Luyi Li, Kaili Liu, Hanyue Zhu, Fikadu Balcha, Yong Fang
Future Microbiology.2024; 19(3): 227. CrossRef - Role of probiotic extracellular vesicles in inter-kingdom communication and current technical limitations in advancing their therapeutic utility
Rahul Sanwlani, Kyle Bramich, Suresh Mathivanan
Extracellular Vesicles and Circulating Nucleic Acids.2024; : 609. CrossRef - Beneficial microbiome and diet interplay in early-onset colorectal cancer
Zhengyuan Zhou, Linda Kleis, Ana Depetris-Chauvin, Stefanie Jaskulski, Victoria Damerell, Karin B Michels, Biljana Gigic, Ute Nöthlings, Gianni Panagiotou
EMBO Molecular Medicine.2024; 17(1): 9. CrossRef - Deciphering the role of host-gut microbiota crosstalk via diverse sources of extracellular vesicles in colorectal cancer
Yun Song, Min Shi, Yugang Wang
Molecular Medicine.2024;[Epub] CrossRef - Targeting the gut and tumor microbiome in cancer treatment resistance
Sona Ciernikova, Aneta Sevcikova, Michal Mego
American Journal of Physiology-Cell Physiology.2024; 327(6): C1433. CrossRef - Lactobacillus plantarum Metabolites Elicit Anticancer Effects by Inhibiting Autophagy-Related Responses
Sihyun Jeong, Yuju Kim, Soyeong Park, Doyeon Lee, Juho Lee, Shwe Phyu Hlaing, Jin-Wook Yoo, Sang Hoon Rhee, Eunok Im
Molecules.2023; 28(4): 1890. CrossRef - Extracellular Vesicles of Probiotics: Shedding Light on the Biological Activity and Future Applications
Paweł Krzyżek, Beatrice Marinacci, Irene Vitale, Rossella Grande
Pharmaceutics.2023; 15(2): 522. CrossRef - Isolation and Characterization of Cow-, Buffalo-, Sheep- and Goat-Milk-Derived Extracellular Vesicles
Monisha Samuel, Rahul Sanwlani, Mohashin Pathan, Sushma Anand, Ella L. Johnston, Ching-Seng Ang, Maria Kaparakis-Liaskos, Suresh Mathivanan
Cells.2023; 12(20): 2491. CrossRef - Gut microbiota in colorectal cancer development and therapy
Chi Chun Wong, Jun Yu
Nature Reviews Clinical Oncology.2023; 20(7): 429. CrossRef - Phytochemicals targeting glycolysis in colorectal cancer therapy: effects and mechanisms of action
Lu Zhan, Fangting Su, Qiang Li, Yueqiang Wen, Feng Wei, Zhelin He, Xiaoyan Chen, Xiang Yin, Jian Wang, Yilin Cai, Yuxia Gong, Yu Chen, Xiao Ma, Jinhao Zeng
Frontiers in Pharmacology.2023;[Epub] CrossRef - Crosstalk between gut microbiota and RNA N6-methyladenosine modification in cancer
Hao Su, Henley Cheung, Harry Cheuk-Hay Lau, Hongyan Chen, Xiaoting Zhang, Na Qin, Yifei Wang, Matthew Tak Vai Chan, William Ka Kei Wu, Huarong Chen
FEMS Microbiology Reviews.2023;[Epub] CrossRef
- Effect of probiotic extracellular vesicles and their applications on health and disease
- Geographic diversity in Helicobacter pylori oipA genotype between Korean and United States isolates
- Aeryun Kim , Jing Lai , D. Scott Merrell , Ji-Hye Kim , Hanfu Su , Jeong-Heon Cha
- J. Microbiol. 2021;59(12):1125-1132. Published online October 31, 2021
- DOI: https://doi.org/10.1007/s12275-021-1450-8
- 65 View
- 0 Download
- 4 Web of Science
- 3 Crossref
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Abstract
- Helicobacter pylori outer membrane inflammatory protein A (OipA) was originally named for its role in inducing inflammation in the host, as evidenced by high mucosal IL-8 levels. Expression of OipA is regulated by phase variation of a CT dinucleotide-repeat located in the 5region of the gene. However, little is known about OipA geographic diversity across isolates. To address this gap, we conducted a large-scale molecular epidemiologic analysis using H. pylori clinical isolates obtained from two geographically distinct populations: Korea and the United States (US). Most Korean isolates (98.7%) possessed two copies of oipA located at two specific loci (A and B) while all US isolates contained only one copy of oipA at locus A. Furthermore, most Korean oipA (94.8%) possessed three or less CT repeats while most US oipA (96.6%) contained five or more CT repeats. Among the two copies, all Korean H. pylori possessed at least one oipA ‘on’ phase variant while the single copy of oipA in US isolates showed 56.2% ‘on’ and 43.8% ‘off.’ Thus, host differences seem to have driven geographic diversification of H. pylori across these populations such that OipA expression in US isolates is still regulated by phase variation with 5 or more CT repeats, while Korean isolates always express OipA; duplication of the oipA combined with a reduction of CT repeats to three or less ensures continued expression. En masse, these findings suggest that diversity in the oipA gene copy number, CT repeats, and phase variation among H. pylori from different populations may confer a benefit in adaptation to particular host populations.
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Citations
Citations to this article as recorded by-
Pathogenicity and virulence of
Helicobacter pylori
: A paradigm of chronic infection
Marguerite Clyne, Tadhg Ó Cróinín
Virulence.2025;[Epub] CrossRef - Genetic diversity of the oipA gene among Helicobacter pylori isolates and clinical outcome in Vietnam
Thi Hong Nhung Thai, Hong Phong Nguyen, Thi Hai Yen Nguyen, Thi Be Hai Nguyen, Thai Hoa Nguyen, Thi Mai Ngan Nguyen, Thi Minh Thi Ha
Infection, Genetics and Evolution.2023; 112: 105438. CrossRef - Characterization of East-Asian Helicobacter pylori encoding Western EPIYA-ABC CagA
Kavinda Tissera, Myeong-A Kim, Jing Lai, Sacheera Angulmaduwa, Aeryun Kim, D. Scott Merrell, Ji-Hye Kim, Hanfu Su, Jeong-Heon Cha
Journal of Microbiology.2022; 60(2): 207. CrossRef
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Pathogenicity and virulence of
Helicobacter pylori
: A paradigm of chronic infection
- Flavihumibacter profundi sp. nov., isolated from eutrophic freshwater sediment
- Ting-Ting Ren , Chun-Zhi Jin , Feng-Jie Jin , Taihua Li , Chang-Jin Kim , Hee-Mock Oh , Hyung-Gwan Lee , Long Jin
- J. Microbiol. 2018;56(7):467-471. Published online June 28, 2018
- DOI: https://doi.org/10.1007/s12275-018-7567-8
- 54 View
- 0 Download
- 11 Crossref
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Abstract
- A Gram-stain-positive, aerobic, non-motile, non-spore-forming, and rod-shaped bacterium, designated strain CHu64- 6-1T, was isolated from a 67-cm-long sediment core collected from the Daechung Reservoir at a water depth of 17-m in Daejeon, Republic of Korea. Comparative 16S rRNA gene sequence studies placed the new isolate in the class Sphingobacteriia, and the isolate is notably most closely related to Flavihumibacter sediminis CJ663T (98.1% similarity), Flavihumibacter solisilvae 3-3T (97.8%), Flavihumibacter petaseus T41T (97.5%), Flavihumibacter cheonanensis WS16T (97.4%), and Flavihumibacter stibioxidans YS-17T (97.2%). The cells of strain CHu64-6-1T formed yellow colonies on R2A agar and contained MK-7 as the only menaquinone, phosphatidylethanolamine, an unidentified phospholipid, and two unidentified aminolipids as the major polar lipids, and C15:0 iso, C17:0 iso 3-OH, C15:1 iso G, and C16:1 ω5c as the major fatty acids (> 5%). The DNA G + C content of the genome was determined to be 46.5 mol%. The DNA-DNA hybridization values of strain CHu64-6-1T with F. sediminis CJ663T, F. solisilvae 3-3T, F. petaseus T41T, F. cheonanensis WS16T, and F. stibioxidans YS-17T were 12.4–33.2%. Based on the combined genotypic and phenotypic data, we propose that strain CHu64-6-1T represents a novel species of the genus Flavihumibacter, for which the name Flavihumibacter profundi sp. nov. is proposed. The type strain is CHu64-6-1T (= KCTC 62290T = CCTCC AB 2018060T).
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Citations
Citations to this article as recorded by-
Flavihumibacter fluminis sp. nov., a novel thermotolerant bacterium isolated from river silt
Bai Guo, Weidong Mu, Sidi Mao, Shucheng Li, Shaomei Yang, Aijv Liu, Shuzhen Wei, Xiuyun Li, Feng Sang, Hongkuan Deng, Yuling Dong, Hongliang Liu, Zhiwei Chen
International Journal of Systematic and Evolutionary Microbiology .2023;[Epub] CrossRef -
Lacibacter sediminis sp. nov., isolated from contaminated freshwater sediment
Ye Zhuo, Chun-Zhi Jin, Feng-Jie Jin, Hee-Mock Oh, Hyung-Gwan Lee, Taihua Li, Long Jin
International Journal of Systematic and Evolutionary Microbiology .2023;[Epub] CrossRef - Flavihumibacter fluminis sp. nov. and Flavihumibacter rivuli sp. nov., isolated from a freshwater stream
Miri S. Park, Hyeonuk Sa, Ilnam Kang, Jang-Cheon Cho
Journal of Microbiology.2022; 60(8): 806. CrossRef - Responses of bacterial communities and organic matter degradation in surface sediment to Macrobrachium nipponense bioturbation
Yiran Hou, Bing Li, Gongcheng Feng, Chengfeng Zhang, Jie He, Haidong Li, Jian Zhu
Science of The Total Environment.2021; 759: 143534. CrossRef - Description of desferrioxamine-producing bacterium Chitinophaga agrisoli sp. nov., isolated from soil
Chun-Zhi Jin, Long Jin, Dong Hyo Kang, Min-Jiao Liu, Jong Min Lee, Dong-Jin Park, Chang-Jin Kim
Antonie van Leeuwenhoek.2021; 114(6): 741. CrossRef - Reactivation of Frozen Stored Microalgal-Bacterial Granular Sludge under Aeration and Non-Aeration Conditions
Yao Shen, Lin Zhu, Bin Ji, Siqi Fan, Yabin Xiao, Yingqun Ma
Water.2021; 13(14): 1974. CrossRef - Positive effects of zeolite powder on aerobic granulation: Nitrogen and phosphorus removal and insights into the interaction mechanisms
Huihua Lin, Rui Ma, Junhao Lin, Shichang Sun, Xiangli Liu, Peixin Zhang
Environmental Research.2020; 191: 110098. CrossRef -
Caulobacter soli sp. nov., isolated from soil sampled at Jiri Mountain, Republic of Korea
Yuanyuan Yang, Chun-Zhi Jin, Feng-Jie Jin, Taihua Li, Jong-Min Lee, Chang-Jin Kim, Hyung-Gwan Lee, Long Jin
International Journal of Systematic and Evolutionary Microbiology .2020; 70(7): 4158. CrossRef -
Lysobacter profundi sp. nov., isolated from freshwater sediment and reclassification of Lysobacter panaciterrae as Luteimonas panaciterrae comb. nov.
Chun-Zhi Jin, Xiuli Song, Yun Ju Sung, Feng-Jie Jin, Taihua Li, Hee-Mock Oh, Hyung-Gwan Lee, Long Jin
International Journal of Systematic and Evolutionary Microbiology .2020; 70(6): 3878. CrossRef - Lacisediminihabitans profunda gen. nov., sp. nov., a member of the family Microbacteriaceae isolated from freshwater sediment
Ye Zhuo, Chun-Zhi Jin, Feng-Jie Jin, Taihua Li, Dong Hyo Kang, Hee-Mock Oh, Hyung-Gwan Lee, Long Jin
Antonie van Leeuwenhoek.2020; 113(3): 365. CrossRef - List of new names and new combinations that have appeared in effective publications outside of the IJSEM and are submitted for valid publication
Aharon Oren, George M. Garrity
International Journal of Systematic and Evolutionary Microbiology .2019;[Epub] CrossRef
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Flavihumibacter fluminis sp. nov., a novel thermotolerant bacterium isolated from river silt
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