Journal of Microbiology

Volume 61(8); August 2023

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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Abstract: 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.

Journal Articles

Mycorrhizal Fungal Diversity Associated with Six Understudied Ectomycorrhizal Trees in the Republic of Korea: Ki Hyeong Park , Seung-Yoon Oh , Yoonhee Cho , Chang Wan Seo , Ji Seon Kim , Shinnam Yoo , Jisun Lim , Chang Sun Kim , Young Woon Lim; J. Microbiol. 2023;61(8):729-739. Published online September 4, 2023; DOI: https://doi.org/10.1007/s12275-023-00073-1

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Abstract: Mycorrhizal fungi are key components of forest ecosystems and play essential roles in host health. The host specificity of mycorrhizal fungi is variable and the mycorrhizal fungi composition for the dominant tree species is largely known but remains unknown for the less common tree species. In this study, we collected soil samples from the roots of six understudied ectomycorrhizal tree species from a preserved natural park in the Republic of Korea over four seasons to investigate the host specificity of mycorrhizal fungi in multiple tree species, considering the abiotic factors. We evaluated the mycorrhizal fungal composition in each tree species using a metabarcoding approach. Our results revealed that each host tree species harbored unique mycorrhizal communities, despite close localization. Most mycorrhizal taxa belonged to ectomycorrhizal fungi, but a small proportion of ericoid mycorrhizal fungi and arbuscular mycorrhizal fungi were also detected. While common mycorrhizal fungi were shared between the plant species at the genus or higher taxonomic level, we found high host specificity at the species/OTU (operational taxonomic unit) level. Moreover, the effects of the seasons and soil properties on the mycorrhizal communities differed by tree species. Our results indicate that mycorrhizal fungi feature host-specificity at lower taxonomic levels.

Fresh Washed Microbiota Transplantation Alters Gut Microbiota Metabolites to Ameliorate Sleeping Disorder Symptom of Autistic Children: Nai-Hua Liu , Hong-Qian Liu , Jia-Yi Zheng , Meng-Lu Zhu , Li-Hao Wu , Hua-Feng Pan , Xing-Xiang He; J. Microbiol. 2023;61(8):741-753. Published online September 4, 2023; DOI: https://doi.org/10.1007/s12275-023-00069-x

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Abstract: Accumulating studies have raised concerns about gut dysbiosis associating autism spectrum disorder (ASD) and its related symptoms. However, the effect of gut microbiota modification on the Chinese ASD population and its underlying mechanism were still elusive. Herein, we enrolled 24 ASD children to perform the first course of fresh washed microbiota transplantation (WMT), 18 patients decided to participate the second course, 13 of which stayed to participate the third course, and there were 8 patients at the fourth course. Then we evaluated the effects of fresh WMT on these patients and their related symptoms. Our results found that the sleeping disorder symptom was positively interrelated to ASD, fresh WMT significantly alleviated ASD and its sleeping disorder and constipation symptoms. In addition, WMT stably and continuously downregulated Bacteroides/ Flavonifractor/Parasutterella while upregulated Prevotella_9 to decrease toxic metabolic production and improve detoxification by regulating glycolysis/myo-inositol/D-glucuronide/D-glucarate degradation, L-1,2-propanediol degradation, fatty acid β-oxidation. Thus, our results suggested that fresh WMT moderated gut microbiome to improve the behavioral and sleeping disorder symptoms of ASD via decrease toxic metabolic production and improve detoxification. Which thus provides a promising gut ecological strategy for ASD children and its related symptoms treatments.

Crystal Structures of Plk1 Polo‑Box Domain Bound to the Human Papillomavirus Minor Capsid Protein L2‑Derived Peptide: Sujin Jung , Hye Seon Lee , Ho-Chul Shin , Joon Sig Choi , Seung Jun Kim , Bonsu Ku; J. Microbiol. 2023;61(8):755-764. Published online September 8, 2023; DOI: https://doi.org/10.1007/s12275-023-00071-3

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Abstract: Human papillomaviruses (HPVs) can increase the proliferation of infected cells during HPV-driven abnormalities, such as cervical cancer or benign warts. To date, more than 200 HPV genotypes have been identified, most of which are classified into three major genera: Alphapapillomavirus, Betapapillomavirus, and Gammapapillomavirus. HPV genomes commonly encode two structural (L1 and L2) and seven functional (E1, E2, E4–E7, and E8) proteins. L2, the minor structural protein of HPVs, not only serves as a viral capsid component but also interacts with various human proteins during viral infection. A recent report revealed that L2 of HPV16 recruits polo-like kinase 1 (Plk1), a master regulator of eukaryotic mitosis and cell cycle progression, for the delivery of viral DNA to mitotic chromatin during HPV16 infection. In this study, we verified the direct and potent interactions between the polo-box domain (PBD) of Plk1 and PBD-binding motif (S–S–pT–P)-containing phosphopeptides derived from L2 of HPV16/HPV18 (high-risk alphapapillomaviruses), HPV5b (low-risk betapapillomavirus), and HPV4 (low-risk gammapapillomavirus). Subsequent structural determination of the Plk1 PBD bound to the HPV18 or HPV4 L2-derived phosphopeptide demonstrated that they interact with each other in a canonical manner, in which electrostatic interactions and hydrogen bonds play key roles in sustaining the complex. Therefore, our structural and biochemical data imply that Plk1 is a broad binding target of L2 of various HPV genotypes belonging to the Alpha-, Beta-, and Gammapapillomavirus genera.

The Regulation of Phosphorus Release by Penicillium chrysogenum in Different Phosphate via the TCA Cycle and Mycelial Morphology: Liyan Wang , Da Tian , Xiaoru Zhang , Mingxue Han , Xiaohui Cheng , Xinxin Ye , Chaochun Zhang , Hongjian Gao , Zhen Li; J. Microbiol. 2023;61(8):765-775. Published online September 4, 2023; DOI: https://doi.org/10.1007/s12275-023-00072-2

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Abstract: Phosphate-solubilizing fungi (PSF) efficiently dissolve insoluble phosphates through the production of organic acids. This study investigates the mechanisms of organic acid secretion by PSF, specifically Penicillium chrysogenum, under tricalcium phosphate ( Ca3(PO4)2, Ca–P) and ferric phosphate ( FePO4, Fe–P) conditions. Penicillium chrysogenum exhibited higher phosphorus (P) release efficiency from Ca-P (693.6 mg/L) than from Fe–P (162.6 mg/L). However, Fe–P significantly enhanced oxalic acid (1193.7 mg/L) and citric acid (227.7 mg/L) production by Penicillium chrysogenum compared with Ca–P (905.7 and 3.5 mg/L, respectively). The presence of Fe–P upregulated the expression of genes and activity of enzymes related to the tricarboxylic acid cycle, including pyruvate dehydrogenase and citrate synthase. Additionally, Fe–P upregulated the expression of chitinase and endoglucanase genes, inducing a transformation of Penicillium chrysogenum mycelial morphology from pellet to filamentous. The filamentous morphology exhibited higher efficiency in oxalic acid secretion and P release from Fe–P and Ca–P. Compared with pellet morphology, filamentous morphology enhanced P release capacity by > 40% and > 18% in Ca–P and Fe–P, respectively. This study explored the strategies employed by PSF to improve the dissolution of different insoluble phosphates.

NEDD4 Regulated Pyroptosis Occurred from Co‑infection between Influenza A Virus and Streptococcus pneumoniae: Jiangzhou You , Linlin Zhou , Xudong San , Hailing Li , Mingyuan Li , Baoning Wang; J. Microbiol. 2023;61(8):777-789. Published online October 4, 2023; DOI: https://doi.org/10.1007/s12275-023-00076-y

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Abstract: Co-infection of respiratory tract viruses and bacteria often result in excess mortality, especially pneumonia caused by influenza viruses and Streptococcus pneumoniae. However, the synergistic mechanisms remain poorly understood. Therefore, it is necessary to develop a clearer understanding of the molecular basis of the interaction between influenza virus and Streptococcus pneumonia. Here, we developed the BALB/c mouse model and the A549 cell model to investigate inflammation and pyroptotic cell death during co-infection. Co-infection significantly activated the NLRP3 inflammasome and induced pyroptotic cell death, correlated with excess mortality. The E3 ubiquitin ligase NEDD4 interacted with both NLRP3 and GSDMD, the executor of pyroptosis. NEDD4 negatively regulated NLRP3 while positively regulating GSDMD, thereby modulating inflammation and pyroptotic cell death. Our findings suggest that NEDD4 may play a crucial role in regulating the GSDMD-mediated pyroptosis signaling pathway. Targeting NEDD4 represents a promising approach to mitigate excess mortality during influenza pandemics by suppressing synergistic inflammation during co-infection of influenza A virus and Streptococcus pneumoniae.

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