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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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  • 1 Web of Science
  • 1 Crossref
AbstractAbstract PDF
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.

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  • Impact of high SAP2 expression on the invasion and adhesion abilities of Candida albicans in vaginal epithelial cells
    Lan Xue, Lu Yang, Xize Fu, Wenli Feng, Jing Yang, Yan Ma, Zhiqin Xi
    Biochemical and Biophysical Research Communications.2025; 777: 152147.     CrossRef
Effect of biostimulation and bioaugmentation on hydrocarbon degradation and detoxification of diesel-contaminated soil: a microcosm study
Patricia Giovanella , Lídia de Azevedo Duarte , Daniela Mayumi Kita , Valéria Maia de Oliveira , Lara Durães Sette
J. Microbiol. 2021;59(7):634-643.   Published online May 15, 2021
DOI: https://doi.org/10.1007/s12275-021-0395-2
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  • 8 Web of Science
  • 7 Crossref
AbstractAbstract PDF
Soil contamination with diesel oil is quite common during processes of transport and storage. Bioremediation is considered a safe, economical, and environmentally friendly approach for contaminated soil treatment. In this context, studies using hydrocarbon bioremediation have focused on total petroleum hydrocarbon (TPH) analysis to assess process effectiveness, while ecotoxicity has been neglected. Thus, this study aimed to select a microbial consortium capable of detoxifying diesel oil and apply this consortium to the bioremediation of soil contaminated with this environmental pollutant through different bioremediation approaches. Gas chromatography (GC-FID) was used to analyze diesel oil degradation, while ecotoxicological bioassays with the bioindicators Artemia sp., Aliivibrio fischeri (Microtox), and Cucumis sativus were used to assess detoxification. After 90 days of bioremediation, we found that the biostimulation and biostimulation/ bioaugmentation approaches showed higher rates of diesel oil degradation in relation to natural attenuation (41.9 and 26.7%, respectively). Phytotoxicity increased in the biostimulation and biostimulation/bioaugmentation treatments during the degradation process, whereas in the Microtox test, the toxicity was the same in these treatments as that in the natural attenuation treatment. In both the phytotoxicity and Microtox tests, bioaugmentation treatment showed lower toxicity. However, compared with natural attenuation, this approach did not show satisfactory hydrocarbon degradation. Based on the microcosm experiments results, we conclude that a broader analysis of the success of bioremediation requires the performance of toxicity bioassays.

Citations

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  • Heavy fuel oil-contaminated soil remediation by individual and bioaugmentation-assisted phytoremediation with Medicago sativa and with cold plasma-treated M. sativa
    Jūratė Žaltauskaitė, Rimas Meištininkas, Austra Dikšaitytė, Laima Degutytė-Fomins, Vida Mildažienė, Zita Naučienė, Rasa Žūkienė, Kazunori Koga
    Environmental Science and Pollution Research.2024; 31(20): 30026.     CrossRef
  • Soil Corrosivity Under Natural Attenuation
    Larissa O. da Silva, Sara H. de Oliveira, Rafael G. C. da Silva, Magda R. S. Vieira, Ivanilda R. de Melo, Severino L. Urtiga Filho
    Materials Research.2024;[Epub]     CrossRef
  • Updating risk remediation-endpoints for petroleum-contaminated soils? A case study in the Ecuadorian Amazon region
    Daniel Hidalgo-Lasso, Karina García-Villacís, Jeaneth Urvina Ulloa, Darwin Marín Tapia, Patricio Gómez Ortega, Frederic Coulon
    Heliyon.2024; 10(9): e30395.     CrossRef
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    Yingying Li, Yuankun Zhao, Yiyang Du, Xuechun Ren, He Ding, Zhimin Wang
    Luminescence.2024;[Epub]     CrossRef
  • Oil biodegradation studies with an immobilized bacterial consortium in plant biomass for the construction of bench-scale bioreactor
    Rachel M. Ferreira, Bernardo D. Ribeiro, Danielle.M.A. Stapelfeldt, Rodrigo P. do Nascimento, Maria de.F.R. Moreira
    Cleaner Chemical Engineering.2023; 6: 100107.     CrossRef
  • Application of Luminescent Bacteria Bioassay in the Detection of Pollutants in Soil
    Kai Zhang, Meng Liu, Xinlong Song, Dongyu Wang
    Sustainability.2023; 15(9): 7351.     CrossRef
  • Salicylate or Phthalate: The Main Intermediates in the Bacterial Degradation of Naphthalene
    Vasili M. Travkin, Inna P. Solyanikova
    Processes.2021; 9(11): 1862.     CrossRef
Extended stability of cyclin D1 contributes to limited cell cycle arrest at G1-phase in BHK-21 cells with Japanese encephalitis virus persistent infection
Ji Young Kim , Soo Young Park , Hey Rhyoung Lyoo , Eung Seo Koo , Man Su Kim , Yong Seok Jeong
J. Microbiol. 2015;53(1):77-83.   Published online January 4, 2015
DOI: https://doi.org/10.1007/s12275-015-4661-z
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AbstractAbstract PDF
There is increasing evidence that many RNA viruses manipulate cell cycle control to achieve favorable cellular environments for their efficient replication during infection. Although virus-induced G0/G1 arrest often delays early apoptosis temporarily, a prolonged replication of the infected virus leads host cells to eventual death. In contrast, most mammalian cells with RNA virus persistent infection often escape cytolysis in the presence of productive viral replication. In this study, we demonstrated that the extended endurance of cyclin D1 was clearly associated with the suppression of glycogen synthase kinase-3β (GSK-3β) expression in BHK-21 cells that are persistently infected with Japanese encephalitis virus (JEV). The G0/G1 arrest of these cells turned much loose compared to the normal BHK-21 cells with JEV acute infection. After cycloheximide treatment, cyclin D1 in the persistently infected cells lasted several hours longer than those in acutely infected cells. Furthermore, both p21Cip1 and p27Kip1, positive regulators for cyclin D1 accumulation in the nucleus, were suppressed in their expression, which contrasts with those in JEV acute infection. Inhibition of the GSK-3β by lithium chloride treatment rescued a significant number of cells from cytolysis in JEV acute infection, which coincided with the levels of cyclin D1 that escaped from proteolysis. Therefore, the limitation of G1/S arrest in the BHK-21 cells with JEV persistent infection is associated with the suppression of GSK-3β expression, resulting in the extended duration of cyclin D1.

Citations

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    Frontiers in Immunology.2020;[Epub]     CrossRef
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    Yao Wang, Shuoxuan Zhao, Yang Chen, Tianying Wang, Chaorun Dong, Xiaoman Wo, Jian Zhang, Yanyan Dong, Weizhen Xu, Xiaofeng Feng, Cong Qu, Yan Wang, Zhaohua Zhong, Wenran Zhao
    Frontiers in Microbiology.2019;[Epub]     CrossRef
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    Luis Filgueira, Nils Lannes
    Pathogens.2019; 8(3): 111.     CrossRef
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    Yi-Lin Chan, Ching-Len Liao, Yi-Ling Lin
    Frontiers in Cellular and Infection Microbiology.2018;[Epub]     CrossRef
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    Ying Fan, Sumana Sanyal, Roberto Bruzzone
    Frontiers in Cellular and Infection Microbiology.2018;[Epub]     CrossRef
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    Yuan Wang, Qing‐Jie Kong, Jin‐Chuan Sun, Xi‐Ming Xu, Yong Yang, Ning Liu, Jian‐Gang Shi
    Journal of Cellular Physiology.2018; 233(7): 5361.     CrossRef
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    Chun-Chun Liu, Yun-Na Zhang, Zhao-Yao Li, Jin-Xiu Hou, Jing Zhou, Lin Kan, Bin Zhou, Pu-Yan Chen, Julie K. Pfeiffer
    Journal of Virology.2017;[Epub]     CrossRef
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    Hao Xu, Zhi-Feng Miao, Zhen-Ning Wang, Ting-Ting Zhao, Ying-Ying Xu, Yong-Xi Song, Jin-Yu Huang, Jun-Yan Zhang, Xing-Yu Liu, Jian-Hua Wu, Hui-Mian Xu
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    Li Liu, Xiao-Ming Zhou, Fang-Fei Yang, Yuan Miao, Yan Yin, Xue-Jun Hu, Gang Hou, Qiu-Yue Wang, Jian Kang
    Oncotarget.2017; 8(37): 62069.     CrossRef
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    Sangmin Kang, Jinjong Myoung
    Journal of Microbiology.2017; 55(5): 319.     CrossRef
Research Support, Non-U.S. Gov't
Helicobacter pylori γ-Glutamyltranspeptidase Induces Cell Cycle Arrest at the G1-S Phase Transition
Kyung-Mi Kim , Seung-Gyu Lee , Jung-Min Kim , Do-Su Kim , Jea-Young Song , Hyung-Lyun Kang , Woo-Kon Lee , Myung-Je Cho , Kwang-Ho Rhee , Hee-Shang Youn , Seung-Chul Baik
J. Microbiol. 2010;48(3):372-377.   Published online June 23, 2010
DOI: https://doi.org/10.1007/s12275-010-9293-8
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AbstractAbstract PDF
In our previous study, we showed that Helicobacter pylori γ-glutamyltranspeptidase (GGT) is associated with H. pylori-induced apoptosis through a mitochondrial pathway. To better understand the role of GGT in apoptosis, we examined the effect of GGT on cell cycle regulation in AGS cells. To determine the effect of recombinant GGT (rGGT) on cell cycle distribution and apoptosis, rGGT-treated and untreated AGS cells were analyzed in parallel by flow cytometry using propidium iodide (PI). We found that rGGT inhibited the growth of AGS cells in a time-dependent manner, and that the pre-exposure of cells to a caspase-3 inhibitor (z-DEVD-fmk) effectively blocked GGT-induced apoptosis. Cell cycle analysis showed G1 phase arrest and apoptosis in AGS cells following rGGT treatment. The rGGT-mediated G1 phase arrest was found to be associated with down-regulation of cyclin E, cyclin A, Cdk 4, and Cdk 6, and the up-regulation of the cyclindependent kinase (Cdk) inhibitors p27 and p21. Our results suggest that H. pylori GGT induces cell cycle arrest at the G1-S phase transition.

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    Lei Zhang, Fei Yu, Yue Zhang, Peifeng Li
    Frontiers in Cellular and Infection Microbiology.2024;[Epub]     CrossRef
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    György Miklós Buzás
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High Dosage of Rok1p, a Putative ATP-dependent RNA Helicase, Leads to a Cell Cycle Arrest at G1/S Stage in Saccharomyces cerevisiae
jeong, Hyun Sook , Oh, Jae Young , Kim, Jin Mi
J. Microbiol. 1998;36(2):139-144.
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AbstractAbstract PDF
The ROK1 gene encodes a putative ATP-dependent RNA helicase which is essential for mitotic cell growth. ROK1 has been thought to affect microtubule and spindle pole body (SPB) functions in Saccharomyces cerevisiae. To investigate the intracellular functions of ROK1, we varied the Rok1 protein dosage in a cell and analyzed its phenotypic effects. Overexpression of the ROK1 gene by using a strong GAL1 promoter was lethal, leading cells to arrest at the unbudded stage. This arrest phenotype is very similar to that of the rok1 null mutation. Indirect immunofluorescence revealed that the majority of arrested cells contained a single SPB. Normas development of microtubules between the duplicated SPSs was rarely observed. Multinuclear cells with abnormal microtubule array were detected in small fraction. Taken together with the phenotype of the rlk1 null mutation, these results imply that ROK1 is required for cell cycle progression at the G1/S stage.
Cell Cycle-dependent Expression of Chitin Synthase Genes in Aspergillus nidulans
Bum-Chan Park , Pil-Jae Maeng , Hee-Moon Park
J. Microbiol. 2001;39(1):74-78.
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AbstractAbstract PDF
The transcription of the chitin synthase genes (chss) was cell cycle-regulated in Aspergillus nidulans and the expression pattern was classified into two groups. Group one, containing chsA and chsC, showed decreasing transcription level upon entry into the S-phase and no further variation during the remainder of the cell cycle. However, group two, containing chsB, chsD, and csmA, showed a sharp decrease of mRNA level upon entry into the G2-phase and an increase during the M-phase. Our results suggested that the chss, belonging to same group with the similar expression pattern during the cell cycle are functionally linked and that chsD may play a role in hyphal growth and development in A. nidulans.

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