Journal of Microbiology

Volume 62(2); February 2024

Journal Articles

miR-135b Aggravates Fusobacterium nucleatum-Induced Cisplatin Resistance in Colorectal Cancer by Targeting KLF13: Wei Zeng , Jia Pan , Guannan Ye; J. Microbiol. 2024;62(2):63-73. Published online February 24, 2024; DOI: https://doi.org/10.1007/s12275-023-00100-1

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Abstract: Cisplatin resistance is the main cause of colorectal cancer (CRC) treatment failure, and the cause has been reported to be related to Fusobacterium nucleatum (Fn) infection. In this study, we explored the role of Fn in regulating cisplatin resistance of CRC cells and its underlying mechanism involved. The mRNA and protein expressions were examined by qRT-PCR and western blot. Cell proliferation and cell apoptosis were assessed using CCK8 and flow cytometry assays, respectively. Dual-luciferase reporter gene assay was adopted to analyze the molecular interactions. Herein, our results revealed that Fn abundance and miR-135b expression were markedly elevated in CRC tissues, with a favorable association between the two. Moreover, Fn infection could increase miR-135b expression via a concentration-dependent manner, and it also enhanced cell proliferation but reduced apoptosis and cisplatin sensitivity by upregulating miR-135b. Moreover, KLF13 was proved as a downstream target of miR-135b, of which overexpression greatly diminished the promoting effect of miR-135b or Fn-mediated cisplatin resistance in CRC cells. In addition, it was observed that upstream 2.5 kb fragment of miR-135b promoter could be interacted by β-catenin/TCF4 complex, which was proved as an effector signaling of Fn. LF3, a blocker of β-catenin/TCF4 complex, was confirmed to diminish the promoting role of Fn on miR-135b expression. Thus, it could be concluded that Fn activated miR-135b expression through TCF4/β-catenin complex, thereby inhibiting KLF13 expression and promoting cisplatin resistance in CRC.

Furan-based Chalcone Annihilates the Multi-Drug-Resistant Pseudomonas aeruginosa and Protects Zebra Fish Against its Infection: Santosh Pushpa Ramya Ranjan Nayak , Catharine Basty , Seenivasan Boopathi , Loganathan Sumathi Dhivya , Khaloud Mohammed Alarjani , Mohamed Ragab Abdel Gawwad , Raghda Hager , Muthu Kumaradoss Kathiravan , Jesu Arockiaraj; J. Microbiol. 2024;62(2):75-89. Published online February 21, 2024; DOI: https://doi.org/10.1007/s12275-024-00103-6

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Abstract: The emergence of carbapenem-resistant Pseudomonas aeruginosa, a multi-drug-resistant bacteria, is becoming a serious public health concern. This bacterium infects immunocompromised patients and has a high fatality rate. Both naturally and synthetically produced chalcones are known to have a wide array of biological activities. The antibacterial properties of synthetically produced chalcone were studied against P. aeruginosa. In vitro, study of the compound (chalcone derivative named DKO1), also known as (2E)-1-(5-methylfuran-2-yl)-3-(4-nitrophenyl) prop-2-en-1-one, had substantial antibacterial and biofilm disruptive action. DKO1 effectively shielded against P. aeruginosa-induced inflammation, oxidative stress, lipid peroxidation, and apoptosis in zebrafish larvae. In adult zebrafish, the treatment enhanced the chances of survivability and reduced the sickness-like behaviors. Gene expression, biochemical analysis, and histopathology studies found that proinflammatory cytokines (TNF-α, IL-1β, IL-6, iNOS) were down regulated; antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT) levels increased, and histoarchitecture was restored in zebrafish. The data indicate that DKO1 is an effective antibacterial agent against P. aeruginosa demonstrated both in vitro and in vivo.

Lactobacillus acidophilus KBL409 Ameliorates Atopic Dermatitis in a Mouse Model: Woon-ki Kim , You Jin Jang , SungJun Park , Sung-gyu Min , Heeun Kwon , Min Jung Jo , GwangPyo Ko; J. Microbiol. 2024;62(2):91-99. Published online February 22, 2024; DOI: https://doi.org/10.1007/s12275-024-00104-5

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Abstract: Atopic dermatitis (AD) is a chronic inflammatory skin disease with repeated exacerbations of eczema and pruritus. Probiotics can prevent or treat AD appropriately via modulation of immune responses and gut microbiota. In this study, we evaluated effects of Lactobacillus acidophilus (L. acidophilus) KBL409 using a house dust mite (Dermatophagoides farinae)-induced in vivo AD model. Oral administration of L. acidophilus KBL409 significantly reduced dermatitis scores and decreased infiltration of immune cells in skin tissues. L. acidophilus KBL409 reduced in serum immunoglobulin E and mRNA levels of T helper (Th)1 (Interferon-γ), Th2 (Interleukin [IL]-4, IL-5, IL-13, and IL-31), and Th17 (IL-17A) cytokines in skin tissues. The anti-inflammatory cytokine IL-10 was increased and Foxp3 expression was up-regulated in AD-induced mice with L. acidophilus KBL409. Furthermore, L. acidophilus KBL409 significantly modulated gut microbiota and concentrations of short-chain fatty acids and amino acids, which could explain its effects on AD. Our results suggest that L. acidophilus KBL409 is the potential probiotic for AD treatment by modulating of immune responses and gut microbiota of host.

Exploring the Therapeutic Potential of Scorpion‑Derived Css54 Peptide Against Candida albicans: Jonggwan Park , Hyeongsun Kim , Da Dam Kang , Yoonkyung Park; J. Microbiol. 2024;62(2):101-112. Published online April 8, 2024; DOI: https://doi.org/10.1007/s12275-024-00113-4

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Abstract: Candida albicans (C. albicans) is one of the most common opportunistic fungi worldwide, which is associated with a high mortality rate. Despite treatment, C. albicans remains the leading cause of life-threatening invasive infections. Consequently, antimicrobial peptides (AMPs) are potential alternatives as antifungal agents with excellent antifungal activity. We previously reported that Css54, found in the venom of Centrurodies suffusus suffusus (C. s. suffusus) showed antibacterial activity against zoonotic bacteria. However, the antifungal activity of Css54 has not yet been elucidated. The obj!ective of this study was to identify the antifungal activity of Css54 against C. albicans and analyze its mechanism. Css54 showed high antifungal activity against C. albicans. Css54 also inhibited biofilm formation in fluconazole-resistant fungi. The antifungal mechanism of action of Css54 was investigated using membrane-related assays, including the membrane depolarization assay and analysis of the membrane integrity of C. albicans after treatment with Css54. Css54 induced reactive oxygen species (ROS) production in C. albicans, which affected its antifungal activity. Our results indicate that Css54 causes membrane damage in C. albicans, highlighting its value as a potential therapeutic agent against C. albicans infection.

Biosynthesis of Chryseno[2,1,c]oxepin‑12‑Carboxylic Acid from Glycyrrhizic Acid in Aspergillus terreus TMZ05‑2, and Analysis of Its Anti‑inflammatory Activity: Liangliang Chen , Lin Zhao , Ju Han , Ping Xiao , Mingzhe Zhao , Sen Zhang , Jinao Duan; J. Microbiol. 2024;62(2):113-124. Published online February 27, 2024; DOI: https://doi.org/10.1007/s12275-024-00105-4

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Abstract: Glycyrrhizic acid, glycyrrhetinic acid, and their oxo, ester, lactone, and other derivatives, are known for their anti-inflammatory, anti-oxidant, and hypoglycemic pharmacological activities. In this study, chryseno[2,1-c]oxepin-12-carboxylic acid (MG) was first biosynthesized from glycyrrhizic acid through sequential hydrolysis, oxidation, and esterification using Aspergillus terreus TMZ05-2, providing a novel in vitro biosynthetic pathway for glycyrrhizic acid derivatives. Assessing the influence of fermentation conditions and variation of strains during culture under stress-induction strategies enhanced the final molar yield to 88.3% (5 g/L glycyrrhizic acid). CCK8 assays showed no cytotoxicity and good cell proliferation, and anti-inflammatory experiments demonstrated strong inhibition of NO release (36.3%, low-dose MG vs. model), transcriptional downregulation of classical effective cellular factors tumor necrosis factor-α (TNF-α; 72.2%, low-dose MG vs. model), interleukin-6 (IL-6; 58.3%, low-dose MG vs. model) and interleukin-1β (IL-1β; 76.4%, low-dose MG vs. model), and decreased abundance of P-IKK-α, P-IKB-α, and P-P65 proteins, thereby alleviating inflammatory responses through the NF-κB pathway in LPS-induced RAW264.7 cells. The findings provide a reference for the biosynthesis of lactone compounds from medicinal plants.

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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Abstract: 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.

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