Journal of Microbiology

Journal Articles

Genetically Engineered CLDN18.2 CAR-T Cells Expressing Synthetic PD1/CD28 Fusion Receptors Produced Using a Lentiviral Vector.: Heon Ju Lee, Seo Jin Hwang, Eun Hee Jeong, Mi Hee Chang; J. Microbiol. 2024;62(7):555-568. Published online May 3, 2024; DOI: https://doi.org/10.1007/s12275-024-00133-0

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Abstract: This study aimed to develop synthetic Claudin18.2 (CLDN18.2) chimeric antigen receptor (CAR)-T (CAR-T) cells as a treatment for advanced gastric cancer using lentiviral vector genetic engineering technology that targets the CLDN18.2 antigen and simultaneously overcomes the immunosuppressive environment caused by programmed cell death protein 1 (PD-1). Synthetic CAR T cells are a promising approach in cancer immunotherapy but face many challenges in solid tumors. One of the major problems is immunosuppression caused by PD-1. CLDN18.2, a gastric-specific membrane protein, is considered a potential therapeutic target for gastric and other cancers. In our study, CLDN18.2 CAR was a second-generation CAR with inducible T-cell costimulatory (CD278), and CLDN18.2-PD1/CD28 CAR was a third-generation CAR, wherein the synthetic PD1/CD28 chimeric-switch receptor (CSR) was added to the second-generation CAR. In vitro, we detected the secretion levels of different cytokines and the killing ability of CAR-T cells. We found that the secretion of cytokines such as interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) secreted by three types of CAR-T cells was increased, and the killing ability against CLDN18.2-positive GC cells was enhanced. In vivo, we established a xenograft GC model and observed the antitumor effects and off-target toxicity of CAR-T cells. These results support that synthetic anti-CLDN18.2 CAR-T cells have antitumor effect and anti-CLDN18.2-PD1/CD28 CAR could provide a promising design strategy to improve the efficacy of CAR-T cells in advanced gastric cancer.

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.

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.

Editorial

Editorial] Bacterial Regulatory Mechanisms for the Control of Cellular Processes: Simple Organisms’ Complex Regulation: Jin-Won Lee; J. Microbiol. 2023;61(3):273-276. Published online April 3, 2023; DOI: https://doi.org/10.1007/s12275-023-00036-6

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Abstract: Bacteria employ a diverse array of cellular regulatory mechanisms to successfully adapt and thrive in ever-changing environments, including but not limited to temperature changes, fluctuations in nutrient availability, the presence or absence of electron acceptors such as oxygen, the availability of metal ions crucial for enzyme activity, and the existence of antibiotics. Bacteria can virtually modulate any step of gene expression from transcr!ptional initiation to posttranslational modification of a protein for the control of cellular processes. Furthermore, one gene regulator often controls another in a complex gene regulatory network. Thus, it is not easy to fully understand the intricacies of bacterial regulatory mechanisms in various environments. In this special issue, while acknowledging the challenge of covering all aspects of bacterial regulatory mechanisms across diverse environments, seven review articles are included to provide insight into the recent progress in understanding such mechanisms from different perspectives: positive regulatory mechanisms by secondary messenger (cAMP receptor protein), two-component signal transduction mechanisms (Rcs and Cpx), diverse regulatory mechanisms by a specific environmental factor in specific bacteria (oxygen availability in Mycobacterium and manganese ion availability in Salmonella), diverse regulatory mechanisms by a specific environmental factor (temperature and antibiotics), and regulatory mechanisms by antibiotics in cell wall synthesis. Bacteria, as ubiquitous organisms that can be found in almost every environment, carry out complex cellular processes that allow them to survive and thrive in a variety of different conditions despite their small size and relative simplicity. One of the key factors that allows bacteria to carry out these complex processes is their ability to regulate gene expression through various mechanisms. Gene expression is a fundamental biological process by which the genetic information encoded in a gene is transcribed into an RNA molecule and subsequently translated into a functional gene product, often a protein. Furthermore, the activity levels of proteins may further be altered by posttranslational modification. Regulation of gene expression refers to the control of the amount and timing of gene expression, and thus it can be divided into transcr!ptional, translational, and posttranslational levels.

Journal Article

Characterization and bioefficacy of green nanosilver particles derived from fungicide-tolerant Tricho-fusant for efficient biocontrol of stem rot (Sclerotium rolfsii Sacc.) in groundnut (Arachis hypogaea L.): Darshna G. Hirpara , Harsukh P. Gajera , Disha D. Savaliya , Rushita V. Bhadani; J. Microbiol. 2021;59(11):1031-1043. Published online October 6, 2021; DOI: https://doi.org/10.1007/s12275-021-1344-9

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Abstract: An efficient and eco-friendly bioefficacy of potent Trichofusant (Fu21) and its green nanosilver formulation against stem rot (Sclerotium rolfsii) in groundnut was established. Fu21 demonstrated higher in-vitro growth inhibition of pathogen with better fungicide tolerance than the parental strains. The green nanosilver particles were synthesized from the extracellular metabolites of Fu21 and characterized for shape (spherical, 59.34 nm in scanning electron microscope), purity (3.00 KeV, energy dispersive X-ray analysis), size (54.3 nm in particle size analyzer), and stability (53.7 mv, zeta). The field efficacy study exhibited that the seedling emergence was high in seeds treated with green nanosilver (minimum inhibitory concentration-[MIC] 20 μg Ag/ml), and a low disease severity index of stem rot during the crop growth was followed by the live antagonist (Fu21) in addition to seed treatment with a fungicide mix under pathogen infestation. The seed quality analysis of harvested pods revealed a high oil content with balanced fatty acid composition (3.10 oleic/linoleic acid ratio) in green nanosilver treatment under pathogen infestation. The residual analysis suggested that green nanosilver applied at the MIC level as seed treatment yielded similar effects as the control for silver residue in the harvested groundnut seeds. The green nanosilver at MIC has a high pod-yield under S. rolfsii infestation, demonstrating green chemistry and sustainability of the nanoproduct.

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