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- [MINIREIVEW] Anti-MRSA agent discovery using Caenorhabditis elegans-based high-throughput screening
- Soo Min Kim , Iliana Escorbar , Kiho Lee , Beth Burgwyn Fuchs , Eleftherios Mylonakis , Wooseong Kim
- J. Microbiol. 2020;58(6):431-444. Published online May 27, 2020
- DOI: https://doi.org/10.1007/s12275-020-0163-8
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- 0 Download
- 9 Web of Science
- 9 Crossref
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Abstract
- Staphylococcus aureus is a leading cause of hospital- and community- acquired infections. Despite current advances in antimicrobial chemotherapy, the infections caused by S. aureus remain challenging due to their ability to readily develop resistance. Indeed, antibiotic resistance, exemplified by methicillin- resistant S. aureus (MRSA) is a top threat to global health security. Furthermore, the current rate of antibiotic discovery is much slower than the rate of antibiotic-resistance development. It seems evident that the conventional in vitro bacterial growth-based screening strategies can no longer effectively supply new antibiotics at the rate needed to combat bacterial antibiotic-resistance. To overcome this antibiotic resistance crisis, screening assays based on host–pathogen interactions have been developed. In particular, the free-living nematode Caenorhabditis elegans has been used for drug screening against MRSA. In this review, we will discuss the general principles of the C. elegans-based screening platform and will highlight its unique strengths by comparing it with conventional antibiotic screening platforms. We will outline major hits from high-throughput screens of more than 100,000 small molecules using the C. elegans–MRSA infection assay and will review the mode-of-action of the identified hit compounds. Lastly, we will discuss the potential of a C. elegansbased screening strategy as a paradigm shift screening platform.
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Citations
Citations to this article as recorded by
- Investigation of anti-aging and anti-infection properties of Jingfang Granules using the Caenorhabditis elegans model
Xin Yin, Yiwei Meng, Chenghong Sun, Yanqiu Zhao, Weitao Wang, Peipei Zhao, Mengmeng Wang, Jingli Ren, Jingchun Yao, Lixin Zhang, Xuekui Xia
Biogerontology.2024; 25(3): 433. CrossRef - Alternatives to animal models to study bacterial infections
Chengming Hu, Wenlong Yang
Folia Microbiologica.2023; 68(5): 703. CrossRef - Gold nanoparticle-DNA aptamer-assisted delivery of antimicrobial peptide effectively inhibits Acinetobacter baumannii infection in mice
Jaeyeong Park, Eunkyoung Shin, Ji-Hyun Yeom, Younkyung Choi, Minju Joo, Minho Lee, Je Hyeong Kim, Jeehyeon Bae, Kangseok Lee
Journal of Microbiology.2022; 60(1): 128. CrossRef - Antimicrobial activity of the membrane-active compound nTZDpa is enhanced at low pH
Soo Min Kim, Guijin Zou, Hyerim Kim, Minjeong Kang, Soyeon Ahn, Hee Young Heo, Jae-Seok Kim, Kyung-Min Lim, Frederick M. Ausubel, Eleftherios Mylonakis, Huajian Gao, Wooseong Kim
Biomedicine & Pharmacotherapy.2022; 150: 112977. CrossRef - Antibiotic resistant bacteria: current situation and treatment options to accelerate the development of a new antimicrobial arsenal
Antonio Tarín-Pelló, Beatriz Suay-García, María-Teresa Pérez-Gracia
Expert Review of Anti-infective Therapy.2022; 20(8): 1095. CrossRef - Therapeutic potentials of endophytes for healthcare sustainability
Ayodeji O. Falade, Kayode E. Adewole, Temitope C. Ekundayo
Egyptian Journal of Basic and Applied Sciences.2021; 8(1): 117. CrossRef -
Novel Immune Modulators Enhance
Caenorhabditis elegans
Resistance to Multiple Pathogens
Nicholas A. Hummell, Alexey V. Revtovich, Natalia V. Kirienko, Paul Dunman
mSphere.2021;[Epub] CrossRef - Caenorhabditis elegans, a Host to Investigate the Probiotic Properties of Beneficial Microorganisms
Cyril Poupet, Christophe Chassard, Adrien Nivoliez, Stéphanie Bornes
Frontiers in Nutrition.2020;[Epub] CrossRef - New Antimicrobial Bioactivity against Multidrug-Resistant Gram-Positive Bacteria of Kinase Inhibitor IMD0354
Iliana E Escobar, Alexis White, Wooseong Kim, Eleftherios Mylonakis
Antibiotics.2020; 9(10): 665. CrossRef
- Investigation of anti-aging and anti-infection properties of Jingfang Granules using the Caenorhabditis elegans model
Journal Article
- Cyclooxygenase Inhibitors Reduce Biofilm Formation and Yeast-Hypha Conversion of Fluconazole Resistant Candida albicans
- E. Abdelmegeed , Mona Ibrahim Shaaban
- J. Microbiol. 2013;51(5):598-604. Published online September 14, 2013
- DOI: https://doi.org/10.1007/s12275-013-3052-6
- 52 View
- 0 Download
- 26 Crossref
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Abstract
- The incidence of fluconazole-resistant Candida albicans has been increasing worldwide. Both biofilm and fungal morphogenesis are main virulence factors of C. albicans cells. Extracellular fungal prostaglandins are synthesized during biofilm adhesion and development and through yeast-hypha conversion. Hence, we targeted prostaglandin synthesis with various cyclooxygenase (COX) inhibitors (aspirin, diclofenac, ketoprofen, tenoxicam, and ketorolac) and assessed their effect on fungal adhesion, biofilm formation, and yeast-hypha conversion in clinical isolates of Fluconazole resistant C. albicans. Significant reduction in fungal adhesion and detachment of mature biofilm was attained down to 1 mM concentrations of anti-inflammatory agents. Microscopical examination of fungal cells in the presence of the tested drugs showed significant reduction of germ tube formation. Therefore, COX inhibitors have a significant effect on reduction of Candida adhesion and biofilm development in correlation with fungal morphogenesis. Moreover, inhibition of C. albicans by COX inhibitors gave synergistic activity with fluconazole suggesting that combination therapeutic strategies may be fruitful for management of infection of Fluconazole resistant C. albicans.
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Citations
Citations to this article as recorded by- Hyphal‐associated protein expression is crucial for Candida albicans‐induced eicosanoid biosynthesis in immune cells
Jana Schimanski, Mark S. Gresnigt, Elena Brunner, Oliver Werz, Bernhard Hube, Ulrike Garscha
European Journal of Immunology.2024;[Epub] CrossRef - Can nonsteroidal anti-inflammatory drugs (NSAIDs) be repurposed for fungal infection?
Fatemeh Babaei, Mohammadreza Mirzababaei, Alireza Tavakkoli, Marjan Nassiri-Asl, Hossein Hosseinzadeh
Naunyn-Schmiedeberg's Archives of Pharmacology.2024; 397(1): 59. CrossRef - Elucidation of the mechanisms of fluconazole resistance and repurposing treatment options against urinary Candida spp. isolated from hospitalized patients in Alexandria, Egypt
Hend Zeitoun, Rawan A. Salem, Nadia M. El-Guink, Nesrin S. Tolba, Nelly M. Mohamed
BMC Microbiology.2024;[Epub] CrossRef - An integrated transcriptomic and metabolomic approach to investigate the heterogeneous Candida albicans biofilm phenotype
Christopher Delaney, Bryn Short, Ranjith Rajendran, Ryan Kean, Karl Burgess, Craig Williams, Carol A. Munro, Gordon Ramage
Biofilm.2023; 5: 100112. CrossRef -
Targeting Adhesion in Fungal Pathogen
Candida Albicans
Harlei Martin, Kevin Kavanagh, Trinidad Velasco-Torrijos
Future Medicinal Chemistry.2021; 13(3): 313. CrossRef - Design, synthesis and biological evaluation of a series of iron and copper chelating deferiprone derivatives as new agents active against Candida albicans
Martina Bortolami, Fabiana Pandolfi, Antonella Messore, Daniele Rocco, Marta Feroci, Roberto Di Santo, Daniela De Vita, Roberta Costi, Paola Cascarino, Giovanna Simonetti, Luigi Scipione
Bioorganic & Medicinal Chemistry Letters.2021; 42: 128087. CrossRef - Aspirin as an Antifungal-Lock Agent in Inhibition of Candidal Biofilm Formation in Surgical Catheters
Alice Kit Ying Chan, Yiu Cheung Tsang, Chun Hung Chu, Chiu Shun Peter Tsang
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Qian Zhang, Fangyan Liu, Meng Zeng, Yingyu Mao, Zhangyong Song
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Franz de Assis Graciano dos Santos, Melyna Chaves Leite-Andrade, Ildnay de Sousa Brandão, Adryelle Idalina da Silva Alves, Maria Daniela Silva Buonafina, Michellangelo Nunes, Luiz Nascimento de Araújo-Neto, Maria Audilene de Freitas, Fábio André Brayner,
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Biofouling.2020; 36(5): 528. CrossRef - Drug Repurposing Strategy against Fungal Biofilms
Thaís Pereira de Mello, Laura Nunes Silva, Lívia de Souza Ramos, Heloísa Freire Frota, Marta Helena Branquinha, André Luis Souza dos Santos
Current Topics in Medicinal Chemistry.2020; 20(7): 509. CrossRef - Aspirin alleviates orthopedic implant‑associated infection
Yi Jiang, Sheng‑Nan Wang, Hang‑Tian Wu, Han‑Jun Qin, Ming‑Liang Ren, Jian‑Chun Lin, Bin Yu
International Journal of Molecular Medicine.2019;[Epub] CrossRef - Metabolomic analysis of low and high biofilm-forming Helicobacter pylori strains
Eric Hong Jian Wong, Chow Goon Ng, Khean Lee Goh, Jamuna Vadivelu, Bow Ho, Mun Fai Loke
Scientific Reports.2018;[Epub] CrossRef - Effects of Rhodomyrtus tomentosa extract on virulence factors of Candida albicans and human neutrophil function
Jutharat Hmoteh, Khadar Syed Musthafa, Supayang Piyawan Voravuthikunchai
Archives of Oral Biology.2018; 87: 35. CrossRef -
Prostaglandin E
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Receptor Antagonist with Antimicrobial Activity against Methicillin-Resistant Staphylococcus aureus
Mélanie A. C. Ikeh, Paul L. Fidel, Mairi C. Noverr
Antimicrobial Agents and Chemotherapy.2018;[Epub] CrossRef - Oral hygiene might prevent cancer
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Francisco Madariaga-Venegas, Roberto Fernández-Soto, Luisa Fernanda Duarte, Nicole Suarez, Daniela Delgadillo, José A. Jara, Ricardo Fernández-Ramires, Blanca Urzúa, Alfredo Molina-Berríos, Sompop Bencharit
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Xinning Liu, Decai Wang, Cuixiang Yu, Tao Li, Jianqiao Liu, Shujuan Sun
Frontiers in Microbiology.2016;[Epub] CrossRef - Neutrophils influx and proinflammatory cytokines inhibition by sodium salicylate, unlike aspirin, in Candida albicans-induced peritonitis model
Priscilla Aparecida Tártari Pereira, Daniel Bini, Fernanda Bovo, Lucia Helena Faccioli, Marta Chagas Monteiro
Folia Microbiologica.2016; 61(4): 337. CrossRef - New frontiers for anti-biofilm drug development
Suzana M. Ribeiro, Mário R. Felício, Esther Vilas Boas, Sónia Gonçalves, Fabrício F. Costa, Ramar Perumal Samy, Nuno C. Santos, Octávio L. Franco
Pharmacology & Therapeutics.2016; 160: 133. CrossRef - Effect of tyrosol on Staphylococcus aureus antimicrobial susceptibility, biofilm formation and virulence factors
H Abdel Rhman Shaymaa, E Rizk Dina
African Journal of Microbiology Research.2016; 10(20): 687. CrossRef - Effect of non-steroidal anti-inflammatory drugs and dexamethazone on the biofilm formation and expression of some adhesion-related genes of Candida albicans and Staphylococcus aureus
Mahmoud Abd El Baky Rehab, G El Gendy Sherein
African Journal of Microbiology Research.2016; 10(20): 694. CrossRef - The roles of CDR1, CDR2, and MDR1 in kaempferol-induced suppression with fluconazole-resistant Candida albicans
Jing Shao, MengXiang Zhang, TianMing Wang, Yue Li, ChangZhong Wang
Pharmaceutical Biology.2016; 54(6): 984. CrossRef - Potent Synergy between Spirocyclic Pyrrolidinoindolinones and Fluconazole against Candida albicans
Ilandari Dewage Udara Anulal Premachandra, Kevin A. Scott, Chengtian Shen, Fuqiang Wang, Shelley Lane, Haoping Liu, David L. Van Vranken
ChemMedChem.2015; 10(10): 1672. CrossRef - Th17 response and its regulation in inflammatory upper airway diseases
Y. Liu, M. Zeng, Z. Liu
Clinical & Experimental Allergy.2015; 45(3): 602. CrossRef -
Role of Pathogen-Derived Cell Wall Carbohydrates and Prostaglandin E
2
in Immune Response and Suppression of Fish Immunity by the Oomycete Saprolegnia parasitica
Rodrigo Belmonte, Tiehui Wang, Gary J. Duncan, Ida Skaar, Hugo Mélida, Vincent Bulone, Pieter van West, Christopher J. Secombes, J. A. Appleton
Infection and Immunity.2014; 82(11): 4518. CrossRef
- Hyphal‐associated protein expression is crucial for Candida albicans‐induced eicosanoid biosynthesis in immune cells
- Partial purification and characterization of β-ketothiolase from Alcaligenes sp. SH-69
- Oh, Deok Hwan , Chung, Chung Wook , Kim, Jeong Yoon , Rhee, Young Ha
- J. Microbiol. 1997;35(4):360-364.
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- 0 Download
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Abstract
- A β-ketothiolase was purified 180-fold from the cell extracts of Alcaligenes sp. SH-69 by a series of chromatography on DEAE-Dephadex A-50, Sephacryl S-200, and hydrozyapatitie columns, The optimum pH values of the partially purified enzyme were 7.5 for condensation reaction and 8.3 for thiolysis reaction. The K_m valued for acetoacetyl-CoA and free CoASH in the thiolusis in the condensation reaction was 0.70mM. The condensation reaction of the β-ketothiolase was inhibited even by low concentrations of free CoASH(K_I= 30.4 uM). Pretreatment of the enzyme with NADH and NADPH markedly inhibited the thiolysis reaction of the enzyme. The potent inhibition of the enzyme by sulfhydryl reagents suggests the involvement of cystein residue in the active site.
- A Recombinant Human [alpha]_1-Antitrypsin Variant, M_malton, Undergoes a Spontaneous Conformational Conversion into a Latent Form
- Chan-Hun Jung , Hana Im
- J. Microbiol. 2003;41(4):335-339.
- 37 View
- 0 Download
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Abstract
- Many genetic variants of [alpha]_1-antitrypsin have been associated with early onset emphysema and liver cirrhosis. However, the detailed structural basis of pathogenic [alpha]_1-antitrypsin molecules is rarely known. Here we found that a recombinant M_malton variant (Phe52-deleted) lost inhibitory activity by spontaneous conformational conversion into a more stable, inactive form under physiological conditions. Biochemical and spectroscopic data suggested that the variant converts into a reactive center loop-inserted conformation, resembling the latent form of plasminogen activator inhibitor-1.
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