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RISS 인기검색어
- 검색키워드
- 저자 : Mylonakis, (검색결과 3 건)
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The effect and irritation of adapalene on Cutibacterium acnes via HTS
( Xiaowen Huang ),( Wen Pan ),( Kang Zeng ),( Eleftherios Mylonakis ) 대한피부과학회 2019 대한피부과학회 학술발표대회집 Vol.71 No.2
Cutibacterium acnes is involved in acne as an opportunistic pathogen. Contrary to the previously thought, the proliferation of C. acnes is not pathogenic crucially. Instead, activation of the innate immunity induced by C. acnes might lead to this chronic inflammation. This research was to establish the screening platform of acne by nematodes and detect the anti-inflammatory activity and stimulation of adapalene. High throughput liquid screening assay was developed here to identify effective anti-infective compounds in 96-well assay plates of worms. Tetracycline was as the positive control to save infected worms in the liquid assay. Minimum inhibitory concentration was presented for visible growth of C. acnes in different conditions. The membrane permeability of C. acnes was detected by monitoring the uptake of SYTOX Green after treating with compounds. We provided results from HTS in nematodes Caenorhabditis elegans that led to the better characterization of adapalene treating acne. Compared to tetracycline, adarotene inhibited the growth of C. acnes significantly (P < 0.01), while adapalene didn’t show anti-C. acnes effect, even under high concentration. Then we found that adapalene reduced the production of pro-inflammatory cytokines (IL-6, IL-8) on PMA stimulated human epidermoid carcinoma cells. But when exposure of human keratinocytes to adapalene, it resulted in the activation of the cells and the secretion of IL-6 and IL-8. The liquid C. elegans - C. acnes assay established here allows screening for anti-acne compounds that are not toxic to hosts. We confirm the utility of C. elegans as a screening platform for acne treatment, and adapalene can rescue C. acnes infected worms. Although it has anti-inflammation effects, adapalene changes the expression of IL-6 and IL-8 depending on the host inflammation conditions. Normal human keratinocytes could be triggered by the stimulation of adapalene.
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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 한국미생물학회 2020 The journal of microbiology Vol.58 No.6
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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AcuD Gene Knockout Attenuates the Virulence of Talaromyces marneffei in a Zebrafish Model
( Jiao Feng ),( Zhiwen Chen ),( Liya He ),( Xing Xiao ),( Chunmei Chen ),( Jieming Chu ),( Eleftherios Mylonakis ),( Liyan Xi ) 한국균학회 2019 Mycobiology Vol.47 No.2
Talaromyces marneffei is the only dimorphic species in its genus and causes a fatal systemic mycosis named talaromycosis. Our previous study indicated that knockdown of AcuD gene (encodes isocitrate lyase of glyoxylate bypass) of T. marneffei by RNA interference approach attenuated the virulence of T. marneffei, while the virulence of the AcuD knockout strains was not studied. In this study, T. marneffei-zebrafish infection model was successfully established through hindbrain microinjection with different amounts of T. marneffei yeast cells. After co-incubated at 28_C, the increasing T. marneffei inoculum doses result in greater larval mortality; and hyphae generation might be one virulence factor involved in T. marneffeizebrafish infection. Moreover, the results demonstrated that the virulence of the DAcuD was significantly attenuated in this Zebrafish infection model.
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