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.

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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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.

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Chalcone derivative enhance poultry meat preservation through quorum sensing inhibition against Salmonella (Salmonella enterica serovar Typhi) contamination
S.P. Ramya Ranjan Nayak, Pratik Pohokar, Anamika Das, L.S. Dhivya, Mukesh Pasupuleti, Ilavenil Soundharrajan, Bader O. Almutairi, Kathiravan Muthu Kumaradoss, Jesu Arockiaraj
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Harnessing Cyclic di-GMP Signaling: A Strategic Approach to Combat Bacterial Biofilm-Associated Chronic Infections
P. Snega Priya, Ramu Meenatchi, Mukesh Pasupuleti, S. Karthick Raja Namasivayam, Jesu Arockiaraj
Current Microbiology.2025;[Epub] CrossRef
Targeted inhibition of PqsR in Pseudomonas aeruginosa PAO1 quorum-sensing network by chalcones as promising antibacterial compounds
Negin Arami, Amineh Sadat Tajani, Maryam Hashemi, Tahoura Rezaei, Razieh Ghodsi, Vahid Soheili, Bibi Sedigheh Fazly Bazzaz
Molecular Biology Reports.2025;[Epub] CrossRef
Exposure to bisphenol A and sodium nitrate found in processed meat induces endocrine disruption and dyslipidemia through PI3K/AKT/SREBP pathway in zebrafish larvae
S. P. Ramya Ranjan Nayak, Anamika Das, Karthikeyan Ramamurthy, Mukesh Pasupuleti, Rajakrishnan Rajagopal, Jesu Arockiaraj
The Journal of Nutritional Biochemistry.2025; : 109887. CrossRef
Testing of Anti-EMT, Anti-Inflammatory and Antibacterial Activities of 2′,4′-Dimethoxychalcone
Peiling Zhao, Mengzhen Xu, Kai Gong, Kaihui Lu, Chen Ruan, Xin Yu, Jiang Zhu, Haixing Guan, Qingjun Zhu
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Furan-based chalcone protects β-cell damage and improves glucose uptake in alloxan-induced zebrafish diabetic model via influencing Peroxisome Proliferator-Activated Receptor agonists (PPAR-γ) signaling
S.P. Ramya Ranjan Nayak, B. Haridevamuthu, Raghul Murugan, L.S. Dhivya, S. Venkatesan, Mikhlid H. Almutairi, Bader O. Almutairi, M.K. Kathiravan, S. Karthick Raja Namasivayam, Jesu Arockiaraj
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S. Madesh, Gokul Sudhakaran, Karthikeyan Ramamurthy, Avra Sau, Kathiravan Muthu Kumaradoss, Mikhlid H. Almutairi, Bader O. Almutairi, Senthilkumar Palaniappan, Jesu Arockiaraj
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Jun Hee Oh, Jonggwan Park, Hee Kyoung Kang, Hee Joo Park, Yoonkyung Park
Biomedicine & Pharmacotherapy.2024; 181: 117724. CrossRef
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B. Aswinanand, S.P. Ramya Ranjan Nayak, S. Madesh, Suthi Subbarayudu, S. Kaliraj, Rajakrishnan Rajagopal, Ahmed Alfarhan, Muthu Kumaradoss Kathiravan, Jesu Arockiaraj
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Characteristics of the gut microbiota colonization, inflammatory profile, and plasma metabolome in intrauterine growth restricted piglets during the first 12 hours after birth: Shimeng Huang , Na Li , Cong Liu , Tiantian Li , Wei Wang , Lili Jiang , Zhen Li , Dandan Han , Shiyu Tao , Junjun Wang; J. Microbiol. 2019;57(9):748-758. Published online June 11, 2019; DOI: https://doi.org/10.1007/s12275-019-8690-x

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Abstract

Intrauterine growth restriction (IUGR) predisposes newborns to inflammatory and metabolic disturbance. Disequilibrium of gut microbiota in early life has been implicated in the incidence of inflammation and metabolic diseases in adulthood. This study aimed to investigate the difference in gut microbiota colonization, cytokines and plasma metabolome between IUGR and normal birth weight (NBW) piglets in early life. At birth, reduced (P < 0.05) body, jejunum, and ileum weights, as well as decreased (P < 0.05) small intestinal villi and increased (P < 0.05) ileal crypt depth were observed in IUGR piglets compared with their NBW counterparts. Imbalanced inflammatory and plasma metabolome profile was observed in IUGR piglets. Furthermore, altered metabolites were mainly involved in fatty acid metabolism and inflammatory response. At 12 h after birth and after suckling colostrum, reduced (P < 0.05) postnatal growth and the small intestinal maturation retardation (P < 0.05) continued in IUGR piglets in comparison with those in NBW littermates. Besides, the gut microbiota structure was significantly altered by IUGR. Importantly, the disruption of the inflammatory profile and metabolic status mainly involved the pro-inflammatory cytokines (IL-1β and IFN-γ) and amino acid metabolism. Moreover, spearman correlation analysis showed that the increased abundance of Escherichia-Shigella and decreased abundance of Clostridium_sensu_stricto_1 in IUGR piglets was closely associated with the alterations of slaughter weight, intestinal morphology, inflammatory cytokines, and plasma metabolites. Collectively, IUGR significantly impairs small intestine structure, modifies gut microbiota colonization, and disturbs inflammatory and metabolic profiles during the first 12 h after birth. The unbalanced gut microbiota mediated by IUGR contributes to the development of inflammation and metabolic diseases.

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Role of putative virulence traits of Campylobacter jejuni in regulating differential host immune responses: Ankita Singh , Amirul Islam Mallick; J. Microbiol. 2019;57(4):298-309. Published online February 22, 2019; DOI: https://doi.org/10.1007/s12275-019-8165-0

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Abstract

Among the major enteric pathogens, Campylobacter jejuni is considered an important source of diarrheal illness in humans. In contrast to the acute gastroenteritis in humans, C. jejuni exhibits prolonged cecal colonization at a high level with little or no pathology in chickens. Although several known virulence determinants of C. jejuni have been found to be associated with a higher degree of pathogenesis in humans, to date, little is known about their functions in the persistent colonization of chickens. The present study was undertaken to assess the role of C. jejuni in imparting differential host immune responses in human and chicken cells. Based on the abundance of major genes encoding virulence factors (GEVFs), we used a particular isolate that harbors the cadF, flaA, peb1, racR, ciaB, cdtB, and hcp genes. This study showed that hypervirulent C. jejuni isolate that encodes a functional type VI secretion system (T6SS) has a greater ability to invade and create characteristic “attaching and effacing” lesions in human INT407 compared to primary chicken embryo intestinal cells (CEICs). Furthermore, we demonstrated that the higher bacterial invasion in human INT407 triggered higher levels of expression of major proinflammatory cytokines, such as IL- 1β and IL-6, and significant downregulation of IL-17A gene expression (P ≤ 0.05). The findings of the present study suggest that the enhanced ability of C. jejuni to invade human cells is tightly regulated by proinflammatory cytokines in the gut and possibly holds the keys to the observed differences in pathogenesis between human and chicken cells.

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Targeted Bioimaging of Microencapsulated Recombinant LAB Vector Expressing Fluorescent Reporter Protein: A Non-invasive Approach for Microbial Tracking
Prakash Biswas, Afruja Khan, Amirul Islam Mallick
ACS Biomaterials Science & Engineering.2024; 10(8): 5210. CrossRef
Identification and functional characterization of putative ligand binding domain(s) of JlpA protein of Campylobacter jejuni
Chandan Gorain, Subhadeep Gupta, S.S. Mahafujul Alam, Mehboob Hoque, Andrey V. Karlyshev, Amirul Islam Mallick
International Journal of Biological Macromolecules.2024; 264: 130388. CrossRef
Heterogeneity and Compositional Diversities of Campylobacter jejuni Outer Membrane Vesicles (OMVs) Drive Multiple Cellular Uptake Processes
Afruja Khan, Avijit Sardar, Pradip K. Tarafdar, Amirul I. Mallick
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Kashaf Javed, Farzana Gul, Rashda Abbasi, Sidra Batool, Zobia Noreen, Habib Bokhari, Sundus Javed
Current Microbiology.2022;[Epub] CrossRef
Gut Microbe-Derived Outer Membrane Vesicles: A Potential Platform to Control Cecal Load of Campylobacter jejuni
Ankita Singh, Afruja Khan, Tamal Ghosh, Samiran Mondal, Amirul I. Mallick
ACS Infectious Diseases.2021; 7(5): 1186. CrossRef
Mucosal delivery of live Lactococcus lactis expressing functionally active JlpA antigen induces potent local immune response and prevent enteric colonization of Campylobacter jejuni in chickens
Chandan Gorain, Ankita Singh, Sudipta Bhattacharyya, Anirban Kundu, Aritraa Lahiri, Subhadeep Gupta, Amirul I. Mallick
Vaccine.2020; 38(7): 1630. CrossRef
Immunopathological properties of the Campylobacter jejuni flagellins and the adhesin CadF as assessed in a clinical murine infection model
Anna-Maria Schmidt, Ulrike Escher, Soraya Mousavi, Nicole Tegtmeyer, Manja Boehm, Steffen Backert, Stefan Bereswill, Markus M. Heimesaat
Gut Pathogens.2019;[Epub] CrossRef
A One Health approach to prevention, treatment, and control of campylobacteriosis
Francesca Schiaffino, James Platts-Mills, Margaret N. Kosek
Current Opinion in Infectious Diseases.2019; 32(5): 453. CrossRef
Immunogenicity and protective efficacy of mucosal delivery of recombinant hcp of Campylobacter jejuni Type VI secretion system (T6SS) in chickens
Ankita Singh, Khairun Nisaa, Sudipta Bhattacharyya, Amirul Islam Mallick
Molecular Immunology.2019; 111: 182. CrossRef

Effect of dietary copper level on the gut microbiota and its correlation with serum inflammatory cytokines in Sprague-Dawley rats: Feng Zhang , Weijiang Zheng , Rong Guo , Wen Yao; J. Microbiol. 2017;55(9):694-702. Published online September 2, 2017; DOI: https://doi.org/10.1007/s12275-017-6627-9

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Abstract

In China’s swine industry, copper is generally supplemented above the National Research Council (NRC) requirement (2012) because of its antimicrobial properties and the potential for growth promotion. Yet few are concerned about whether this excess supplementation is necessary. In this study, the 16S rRNA pyrosequencing was designed and used to investigate the effect of dietary copper level on the diversity of the fecal microbial community and the correlation of copper level with the serum level of inflammatory cytokines in Sprague-Dawley rat models. The results showed that the diet containing a high level of Cu (120 and 240 mg/kg) changed the microbial richness and diversity of rat feces associated with the increased copper content in the rat ileac and colonic digesta. Furthermore, a Pearson’s correlation analysis indicated that an accumulation of unabsorbed copper in the chyme was correlated with the microbial composition of the rat feces, which was linked with TNF-α in serum. The results suggest that dietary copper level may have a direct impact on circulating inflammatory cytokines in the serum, perhaps inducing an inflammatory response by altering the microbial composition of rat feces. Serum TNF-α could be the chief responder to excessive copper exposure.

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Research Support, Non-U.S. Gov't

Comparative Analysis of Immune Responses to Mycobacterium abscessus Infection and Its Antigens in Two Murine Models: Bo-Young Jeon , Jeongyeon Kwak , Seung-Sub Lee , SangNae Cho , Chul Jae Won , Jin Man Kim , Sung Jae Shin; J. Microbiol. 2009;47(5):633-640. Published online October 24, 2009; DOI: https://doi.org/10.1007/s12275-009-0139-1

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Abstract: Mycobacterium abscessus has been identified as an emerging pulmonary pathogen in humans. Because little is known regarding immune responses elicited by M. abscessus or its antigens, immunological responses were studied in two murine models subjected to intravenous (high-dose or systemic infection) or pulmonary (low-dose or local infection) inoculation with M. abscessus ATCC 19977. An overall comparison between the two models showed similar patterns of bacterial survival and host immune responses. The colonization of M. abscessus was the highest at 5 days post-infection (dpi) and its elimination was positively correlated with cell-mediated immunity in both challenges. However, an inverse relationship was observed between progressive inflammation and mycobacterial colonization levels in mice infected with a high dose at 14 dpi. Regarding antigens, culture filtrate (CF) of M. abscessus strongly induced IFN-γ secretion, whereas cellular extract (CE) antigen elicited strong antibody responses. The antibody response to M. abscessus antigens in mice subjected to low-dose infection increased when the cellular immune response decreased over 14 dpi. However, the antibody response for the high-dose infection increased promptly after the infection. In comparison of cytokine expression in lung homogenates after M. abscessus infection, Th1 and Th2 cytokines increased simultaneously in the high-dose infection, whereas only cell-mediated immunity developed in the low-dose pulmonary infection. These findings not only enhance our understanding of the immune response to M. abscessus infection according to systemic or pulmonary infection, but may also aid in immunological diagnosis and vaccine development.

Anti-tumor Activity of the Fruitbody Extract of Basidiomycete, Phellinus linteus: Jong-Soon Lim , Seung-Hyung Kim , Jin-Seo Park , Jeong-Youl Choi , Seong Joo Park , Kwang-Soo Shin; J. Microbiol. 2001;39(2):121-125.

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Abstract: Methanol extract prepared from the fruitbody of Phellinus linteus (EPL) showed anti-tumor and immuno-stimulating activities. The invasion activity of B16-F10 melanoma cells through a reconstituted basement membrane to the collagen-coated lower surface of the filters was inhibited about 67% by EPL (100 ug/ml). Also, EPL inhibited the expression of the mRNA for MMP-2 and MMP-9. In vivo treatment of C57BL/6 mice (150 mg/kg) with EPL for 14 days, the pulmonary colonization was found to be inhibited about 75%. Using reverse transcriptionpolymerase chain reaction (RT-PCR) analysis, we found that cytokine IL-12 and INF-[gamma] genes were induced by EPL. Furthermore, EPL stimulated the proliferation of CD4^+ (33.5%) and CD8^+ (17.7%) in mouse splenocytes.

Cytokine-Inducing and T Cell Mitogenic Effects of Cordyceps hepialidicola: Jong-Soon Lim , Seung-Hyung Kim , Jeong-Youl Choi , Jin-Seo Park , Seong Joo Park , Kwang-Soo Shin; J. Microbiol. 2001;39(3):181-185.

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Abstract: The morphological characteristics of newly isolated Cordyceps hepialidicola were characterized, and the phylogenetic relationships with other Cordyceps species were investigated using a sequence analysis of the internal transcribed spacer (ITS). The PCR product of 592 bp showed a homology of 92 and 91% with C. militaris and C. nutans, respectively. In an in vitro model using mouse peripheral blood mononuclear cells (PBMC), a methanol extract of C. hepialidicola induced multiple cytokines, including IFN-[gamma], IL-4, and IL-18. The extract also enhanced the percentages of the CD4^+ and CD8^+ T cells in the healthy murine PBMCs to 56.1% and 13.0%, respectively. The percentages of CD4^+ and CD8^+ in the untreated controls were 28.4 and 7.3%, and concanavalin A-treated positive controls were 62.4 and 18.3%, respectively.

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