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Hydroxychloroquine an Antimalarial Drug, Exhibits Potent Antifungal Efficacy Against Candida albicans Through Multitargeting
Sargun Tushar Basrani, Tanjila Chandsaheb Gavandi, Shivani Balasaheb Patil, Nandkumar Subhash Kadam, Dhairyasheel Vasantrao Yadav, Sayali Ashok Chougule, Sankunny Mohan Karuppayil, Ashwini Khanderao Jadhav
J. Microbiol. 2024;62(5):381-391.   Published online April 8, 2024
DOI: https://doi.org/10.1007/s12275-024-00111-6
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AbstractAbstract
Candida albicans is the primary etiological agent associated with candidiasis in humans. Unrestricted growth of C. albicans can progress to systemic infections in the worst situation. This study investigates the antifungal activity of Hydroxychloroquine (HCQ) and mode of action against C. albicans. HCQ inhibited the planktonic growth and yeast to hyphal form morphogenesis of C. albicans significantly at 0.5 mg/ml concentration. The minimum inhibitory concentrations (MIC(50)) of HCQ for C. albicans adhesion and biofilm formation on the polystyrene surface was at 2 mg/ml and 4 mg/ml respectively. Various methods, such as scanning electron microscopy, exploration of the ergosterol biosynthesis pathway, cell cycle analysis, and assessment of S oxygen species (ROS) generation, were employed to investigate HCQ exerting its antifungal effects. HCQ was observed to reduce ergosterol levels in the cell membranes of C. albicans in a dose-dependent manner. Furthermore, HCQ treatment caused a substantial arrest of the C. albicans cell cycle at the G0/G1 phase, which impeded normal cell growth. Gene expression analysis revealed upregulation of SOD2, SOD1, and CAT1 genes after HCQ treatment, while genes like HWP1, RAS1, TEC1, and CDC 35 were downregulated. The study also assessed the in vivo efficacy of HCQ in a mice model, revealing a reduction in the pathogenicity of C. albicans after HCQ treatment. These results indicate that HCQ holds for the development of novel antifungal therapies.
Microbial co-occurrence network in the rhizosphere microbiome: its association with physicochemical properties and soybean yield at a regional scale
Sarbjeet Niraula , Meaghan Rose , Woo-Suk Chang
J. Microbiol. 2022;60(10):986-997.   Published online September 27, 2022
DOI: https://doi.org/10.1007/s12275-022-2363-x
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AbstractAbstract
Microbial communities in the rhizosphere play a crucial role in determining plant growth and crop yield. A few studies have been performed to evaluate the diversity and co-occurrence patterns of rhizosphere microbiomes in soybean (Glycine max) at a regional scale. Here, we used a culture-independent
method
to compare the bacterial communities of the soybean rhizosphere between Nebraska (NE), a high-yield state, and Oklahoma (OK), a low-yield state. It is well known that the rhizosphere microbiome is a subset of microbes that ultimately get colonized by microbial communities from the surrounding bulk soil. Therefore, we hypothesized that differences in the soybean yield are attributed to the variations in the rhizosphere microbes at taxonomic, functional, and community levels. In addition, soil physicochemical properties were also evaluated from each sampling site for comparative study. Our result showed that distinct clusters were formed between NE and OK in terms of their soil physicochemical property. Among 3 primary nutrients (i.e., nitrogen, phosphorus, and potassium), potassium is more positively correlated with the high-yield state NE samples. We also attempted to identify keystone communities that significantly affected the soybean yield using co-occurrence network patterns. Network analysis revealed that communities formed distinct clusters in which members of modules having significantly positive correlations with the soybean yield were more abundant in NE than OK. In addition, we identified the most influential bacteria for the soybean yield in the identified modules. For instance, included are class Anaerolineae, family Micromonosporaceae, genus Plantomyces, and genus Nitrospira in the most complex module (ME9) and genus Rhizobium in ME23. This research would help to further identify a way to increase soybean yield in low-yield states in the U.S. as well as worldwide by reconstructing the microbial communities in the rhizosphere.

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Citations to this article as recorded by  
  • The rhizosphere microbiome of 51 potato cultivars with diverse plant growth characteristics
    Benoit Renaud Martins, Viviane Radl, Krzysztof Treder, Dorota Michałowska, Karin Pritsch, Michael Schloter
    FEMS Microbiology Ecology.2024;[Epub]     CrossRef
  • Response of Soil Microorganisms and Phenolic to Pseudostelariae heterophylla Cultivation in Different Soil Types
    Yingying Liu, Dan Wu, Yongjun Kan, Li Zhao, Chang Jiang, Wensheng Pang, Juan Hu, Meilan Zhou
    Eurasian Soil Science.2024; 57(3): 446.     CrossRef
  • Analysis of the rhizosphere bacterial diversity of Angelica dahurica var. formosana from different experimental sites and varieties (strains)
    Meiyan Jiang, Fei Yao, Yunshu Yang, Yang Zhou, Kai Hou, Yinyin Chen, Dongju Feng, Wei Wu
    PeerJ.2023; 11: e15997.     CrossRef
  • Long-term fertilization coupled with rhizobium inoculation promotes soybean yield and alters soil bacterial community composition
    Wanling Wei, Dawei Guan, Mingchao Ma, Xin Jiang, Fenliang Fan, Fangang Meng, Li Li, Baisuo Zhao, Yubin Zhao, Fengming Cao, Huijun Chen, Jun Li
    Frontiers in Microbiology.2023;[Epub]     CrossRef
Lipocalin2 as a potential antibacterial drug against Acinetobacter baumannii infection
Daejin Lim , Su-Jin Park , Ha Young Kim , Minsang Shin , Miryoung Song
J. Microbiol. 2022;60(4):444-449.   Published online March 28, 2022
DOI: https://doi.org/10.1007/s12275-022-2007-1
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AbstractAbstract
Available antibiotics to treat Acinetobacter baumannii infection is limited due to increasing resistance and the emergence of multiple drug-resistant strains. Hence, discovering effective agents against A. baumannii to reduce the number of infectionrelated deaths is imperative. In search of novel and alternative antibiotics, the antibacterial function of lipocalin2 (Lcn2) was investigated to treat systemic infections of A. baumannii using a mouse neutropenia model. We observed a significant increase in serum Lcn2 levels upon bacterial injection into the mouse, and the administration of recombinant Lcn2 (rmLcn2) extended their survival. Such protective effects were also observed in rmLcn2-pretreated macrophages, where rmLcn2 reduced the survival of the pathogen inside the macrophages. The underlying molecular mechanism of Lcn2 protection was also investigated. We observed that pretreatment of the Raw- 264.7 macrophages with rmLcn2 markedly altered the expression of tonB3, which encodes a component of the transporter for ferrisiderophores in A. baumannii. However, the expression of katG, the gene encoding catalase, remained unaffected. These indicate that Lcn2-mediated defense against the pathogen is related to nutritional immunity rather than reactive oxygen species (ROS) production. Furthermore, the addition of rmLcn2 in infected mice diminished bacterial burden in multiple organs and enhanced the expression of tonB3 in the liver, spleen, and lungs of the infected mice. Increased survival rate due to rmLcn2 treatment declined when the infection model was established using lcn2-defective (lcn2-/-) mice, which indicated the necessity of endogenous Lcn2. Therefore, the antibacterial function of Lcn2 can be exploited to develop an alternative therapeutic agent against A. baumannii.

Citations

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  • Antimicrobial peptide thanatin fused endolysin PA90 (Tha-PA90) for the control of Acinetobacter baumannii infection in mouse model
    Jeonghyun Lim, Heejoon Myung, Daejin Lim, Miryoung Song
    Journal of Biomedical Science.2024;[Epub]     CrossRef
  • Dynamic changes and clinical value of lipocalin 2 in liver diseases caused by microbial infections
    Feng Chen, Shan-Shan Wu, Chao Chen, Cheng Zhou
    World Journal of Hepatology.2024; 16(2): 177.     CrossRef
  • Lipocalin-2 is an essential component of the innate immune response to Acinetobacter baumannii infection
    Jessica R. Sheldon, Lauren E. Himmel, Dillon E. Kunkle, Andrew J. Monteith, K. Nichole Maloney, Eric P. Skaar, David S. Weiss
    PLOS Pathogens.2022; 18(9): e1010809.     CrossRef
Antiviral effects of human placenta hydrolysate (Laennec) against SARS-CoV-2 in vitro and in the ferret model
Eun-Ha Kim , Young-il Kim , Seung-Gyu Jang , Minju Im , Kyeongsoo Jeong , Young Ki Choi , Hae-Jung Han
J. Microbiol. 2021;59(11):1056-1062.   Published online October 6, 2021
DOI: https://doi.org/10.1007/s12275-021-1367-2
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  • 6 Web of Science
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AbstractAbstract
The COVID-19 pandemic has caused unprecedented health, social, and economic crises worldwide. However, to date, there is an only a limited effective treatment for this disease. Human placenta hydrolysate (hPH) has previously been shown to be safe and to improve the health condition in patients with hyperferritinemia and COVID-19. In this study, we aimed to determine the antiviral effects of hPH against SARS-CoV-2 in vitro and in vivo models and compared with Remdesivir, an FDA-approved drug for COVID-19 treatment. To assess whether hPH inhibited SARS-CoV-2 replication, we determined the CC50, EC50, and selective index (SI) in Vero cells by infection with a SARS-CoV-2 at an MOI of 0.01. Further, groups of ferrets infected with 105.8 TCID50/ml of SARS-CoV-2 and treated with hPH at 2, 4, 6 dpi, and compared their clinical manifestation and virus titers in respiratory tracts with PBS control-treated group. The mRNA expression of immunerelated cytokines was determined by qRT-PCR. hPH treatment attenuated virus replication in a dose-dependent manner in vitro. In a ferret infection study, treatment with hPH resulted in minimal bodyweight loss and attenuated virus replication in the nasal wash, turbinates, and lungs of infected ferrets. In addition, qRT-PCR results revealed that the hPH treatment remarkably upregulated the gene expression of type I (IFN-α and IFN-β) and II (IFN-γ) IFNs in SARS-CoV-2 infected ferrets. Our data collectively suggest that hPH has antiviral efficacy against SARS-CoV-2 and might be a promising therapeutic agent for the treatment of SARS-CoV-2 infection.

Citations

Citations to this article as recorded by  
  • Perinatal Hypoxia and Immune System Activation in Schizophrenia Pathogenesis: Critical Considerations During COVID-19 Pandemic
    I Kawikova, K Hakenova, M Lebedeva, L Kleteckova, L Jakob, V Spicka, L Wen, F Spaniel, K Vales
    Physiological Research.2024; : S615.     CrossRef
  • Human Placenta Extract (HPH) Suppresses Inflammatory Responses in TNF-α/IFN-γ-Stimulated HaCaT Cells and a DNCB Atopic Dermatitis (AD)-Like Mouse Model
    Jung Ok Lee, Youna Jang, A Yeon Park, Jung Min Lee, Kyeongsoo Jeong, So-Hyun Jeon, Hui Jin, Minju Im, Jae-Won Kim, Beom Joon Kim
    Journal of Microbiology and Biotechnology.2024; 34(10): 1969.     CrossRef
  • Systematic analysis of the pharmacology of standardized extracts of human placenta
    T. E. Bogacheva, I. Yu. Torshin, O. A. Gromova
    Pharmacokinetics and Pharmacodynamics.2024; (4): 3.     CrossRef
  • Distinctive Combinations of RBD Mutations Contribute to Antibody Evasion in the Case of the SARS-CoV-2 Beta Variant
    Tae-Hun Kim, Sojung Bae, Sunggeun Goo, Jinjong Myoung
    Journal of Microbiology and Biotechnology.2023; 33(12): 1587.     CrossRef
  • Current state-of-the-art and potential future therapeutic drugs against COVID-19
    Ailong Sha, Yi Liu, Haiyan Hao
    Frontiers in Cell and Developmental Biology.2023;[Epub]     CrossRef
  • SARS-CoV-2 Aerosol and Intranasal Exposure Models in Ferrets
    Elizabeth E. Zumbrun, Samantha E. Zak, Eric D. Lee, Philip A. Bowling, Sara I. Ruiz, Xiankun Zeng, Jeffrey W. Koehler, Korey L. Delp, Russel R. Bakken, Shannon S. Hentschel, Holly A. Bloomfield, Keersten M. Ricks, Tamara L. Clements, April M. Babka, John
    Viruses.2023; 15(12): 2341.     CrossRef
  • Human placenta hydrolysates: from V.P. Filatov to the present day: Review
    Olga A. Gromova, Ivan Yu. Torshin, Alexander G. Chuchalin, Valeriy А. Maximov
    Terapevticheskii arkhiv.2022; 94(3): 434.     CrossRef

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