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Seo, Hoonhee,Al mahmud, Hafij,Kim, Sukyung,Islam, Md Imtiazul,Lee, Kee-In,Gil, Young Sig,Song, Ho-Yeon Elsevier 2018 Regulatory toxicology and pharmacology Vol.95 No.-
<P><B>Abstract</B></P> <P>The infectious disease tuberculosis remains a serious global health issue and is responsible for nearly 1.8 million deaths every year. In our previous study, DFC-2 was confirmed to show anti-tubercular activity against drug-susceptible and drug-resistant strains of <I>Mycobacterium tuberculosis</I>. To support the safety-in-use of DFC-2 as an anti-tubercular drug, DFC-2 was tested via single- and 28-day repeated-dose oral toxicity study and mutagenicity assays. In the oral toxicity study, a single oral dose of DFC-2 at 2000 mg/kg did not produce deaths or abnormal lesions in the internal organs of rats. The results of a 28-day orally repeated dose of DFC-2 did not show treatment-related deaths or obvious toxicity symptoms in the animals treated with a dose of 300 mg/kg/day during the experimental period. Therefore, the no-observed-adverse-effect level (NOAEL) of DFC-2 was determined as 300 mg/kg/day for both male and female rats. In addition, DFC-2 showed no genetic toxicity in <I>in vitro</I> bacterial reverse mutation test, <I>in vitro</I> chromosomal aberration test, and in vivo mouse bone marrow micronucleus formation test. These results indicate that DFC-2 is a promising anti-tubercular drug candidate with a favorable safety profile.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Oral toxicity (acute, subchronic) and genotoxicity of a new antitubercular drug candidate, DFC-2, was investigated in rats. </LI> <LI> No acute oral toxicity or adverse effects were observed at dosages up to 2000 mg/kg body weight. </LI> <LI> NOAEL (No observed adverse effect level) for subchronic toxicity (28 days) in rats is 300 mg/kg/day. </LI> <LI> Negative outcomes obtained in the genotoxicity tests. </LI> </UL> </P>
이영경,Seo Hoonhee,Kim Sukyung,Rahim MD Abdur,Yoon Youjin,Jung Jehee,Lee Saebim,Ryu Chang Beom,Song Ho-Yeon 한국미생물학회 2021 The journal of microbiology Vol.59 No.11
Tuberculosis, an infectious disease, is caused by Mycobacterium tuberculosis. It remains a significant public health issue around the globe, causing about 1.8 million deaths every year. Drug-resistant M. tuberculosis, including multi-drug-resistant (MDR), extremely-drug-resistant (XDR), and totally drugresistant (TDR) M. tuberculosis, continues to be a threat to public health. In the case of antibiotic-resistant tuberculosis, the treatment effect of conventional antibiotics is low. Side effects caused by high doses over a long period are causing severe problems. To overcome these problems, there is an urgent need to develop a new anti-tuberculosis drug that is different from the existing compound-based antibiotics. Probiotics are defined as live microorganisms conferring health benefits. They can be potential therapeutic agents in this context as the effectiveness of probiotics against different infectious diseases has been well established. Here, we report that Lactobacillus crispatus PMC201 shows a promising effect on tuberculosis isolated from vaginal fluids of healthy Korean women. Lactobacillus crispatus PMC201 reduced M. tuberculosis H37Rv under co-culture conditions in broth and reduced M. tuberculosis H37Rv and XDR M. tuberculosis in macrophages. Lactobacillus crispatus PMC201 was not toxic to a guinea pig model and did not induce dysbiosis in a human intestinal microbial ecosystem simulator. Taken together, these results indicate that L. crispatus PMC201 can be a promising alternative drug candidate in the current tuberculosis drug regime. Further study is warranted to assess the in vivo efficacy and confirm the mode of action of L. crispatus PMC201.
( Sukyung Kim ),( Hoonhee Seo ),( Hafij Al Mahmud ),( Md Imtiazul Islam ),( Omme Fatema Sultana ),( Youngkyoung Lee ),( Minhee Kim ),( Ho-yeon Song ) 한국미생물 · 생명공학회 2020 Journal of microbiology and biotechnology Vol.30 No.7
Overproduction and accumulation of melanin in the skin will darken the skin and cause skin disorders. So far, components that can inhibit tyrosinase, a melanin synthase of melanocytes, have been developed and used as ingredients of cosmetics or pharmaceutical products. However, most of existing substances can only inhibit the biosynthesis of melanin while melanin that is already synthesized and deposited is not directly decomposed. Thus, their effects in decreasing melanin concentration in the skin are weak. To overcome the limitation of existing therapeutic agents, we started to develop a substance that could directly biodegrade melanin. We screened traditional fermented food microorganisms for their abilities to direct biodegrade melanin. As a result, we found that a kimchi-derived Pediococcus acidilactici PMC48 had a direct melanin-degrading effect. This PMC48 strain is a new strain, different from P. acidilactici strains reported so far. It not only directly degrades melanin, but also has tyrosinase-inhibiting effect. It has a direct melanin-decomposition effect. It exceeds existing melanin synthesis-inhibiting technology. It is expected to be of high value as a raw material for melanin degradation drugs and cosmetics.
( Hanieh Tajdozian ),( Hoonhee Seo ),( Sukyung Kim ),( Md Abdur Rahim ),( Saebim Lee ),( Ho-yeon Song ) 한국미생물 · 생명공학회 2021 Journal of microbiology and biotechnology Vol.31 No.10
Carbapenem-resistant Enterobacteriaceae (CRE) that produce Klebsiella pneumoniae carbapenemase are increasingly reported worldwide and have become more and more resistant to nearly all antibiotics during the past decade. The emergence of K. pneumoniae strains with decreased susceptibility to carbapenems, which are used as a last resort treatment option, is a significant threat to hospitalized patients worldwide as K. pneumoniae infection is responsible for a high mortality rate in the elderly and immunodeficient individuals. This study used Lactobacillus fermentum as a candidate probiotic for treating CRE-related infections and investigated its effectiveness. We treated mice with L. fermentum originating from the vaginal fluid of a healthy Korean woman and evaluated the Lactobacilli’s efficacy in preventive, treatment, nonestablishment, and colonization mouse model experiments. Compared to the control, pre-treatment with L. fermentum significantly reduced body weight loss in the mouse models, and all mice survived until the end of the study. The oral administration of L. fermentum after carbapenemresistant Klebsiella (CRK) infection decreased mortality and illness severity during a 2-week observation period and showed that it affects other strains of CRK bacteria. Also, the number of Klebsiella bacteria was decreased to below 5.5 log10 CFU/ml following oral administration of L. fermentum in the colonization model. These findings demonstrate L. fermentum’s antibacterial activity and its potential to treat CRE infection in the future.
Changes in the Microbiome of Vaginal Fluid after Menopause in Korean Women
( Sukyung Kim ),( Hoonhee Seo ),( Md Abdur Rahim ),( Saebim Lee ),( Yun-sook Kim ),( Ho-yeon Song ) 한국미생물 · 생명공학회 2021 Journal of microbiology and biotechnology Vol.31 No.11
Various microorganisms reside in the human vagina; the vaginal microbiome is closely linked to both vaginal and general health, and for this reason, microbiome studies of the vagina are an area of research. In this study, we analyzed the vaginal microbiome of women before and after menopause to further increase our understanding of the vaginal microbiome and its contribution to general health. We did a 16s rRNA gene-based metagenomic analysis on the vaginal fluids of 11 premenopausal and 19 postmenopausal women in Korea. We confirmed that the taxonomic composition was significantly different between the two groups. In postmenopausal women, species richness was significantly decreased, but species diversity was significantly increased. In particular, among the taxonomic components corresponding to all taxon ranks of the vaginal microbiome, a reduction in Lactobacillus taxa after menopause contributed the most to the difference between the two groups. In addition, we confirmed through metabolic analysis that the lactic-acid concentration was also decreased in the vaginal fluid of women after menopause. Our findings on the correlation between menopause and the microbiome could help diagnose menopause and enhance the prevention and treatment diseases related to menopause.
( Youjin Yoon ),( Hoonhee Seo ),( Sukyung Kim ),( Youngkyoung Lee ),( Md Abdur Rahim ),( Saebim Lee ),( Ho-yeon Song ) 한국미생물 · 생명공학회 2021 Journal of microbiology and biotechnology Vol.31 No.12
Tuberculosis is a highly contagious disease caused by Mycobacterium tuberculosis. It affects about 10 million people each year and is still one of the leading causes of death worldwide. About 2 to 3 billion people (equivalent to 1 in 3 people in the world) are infected with latent tuberculosis. Moreover, as the number of multidrug-resistant, extensively drug-resistant, and totally drug-resistant strains of M. tuberculosis continues to increase, there is an urgent need to develop new anti-tuberculosis drugs that are different from existing drugs to combat antibiotic-resistant M. tuberculosis. Against this background, we aimed to develop new anti-tuberculosis drugs using probiotics. Here, we report the anti-tuberculosis effect of Pediococcus acidilactici PMC202 isolated from young radish kimchi, a traditional Korean fermented food. Under coculture conditions, PMC202 inhibited the growth of M. tuberculosis. In addition, PMC202 inhibited the growth of drug-sensitive and -resistant M. tuberculosis- infected macrophages at a concentration that did not show cytotoxicity and showed a synergistic effect with isoniazid. In a 2-week, repeated oral administration toxicity study using mice, PMC202 did not cause weight change or specific clinical symptoms. Furthermore, the results of 16S rRNA-based metagenomics analysis confirmed that dysbiosis was not induced in bronchoalveolar lavage fluid after oral administration of PMC202. The anti-tuberculosis effect of PMC202 was found to be related to the reduction of nitric oxide. Our findings indicate that PMC202 could be used as an anti-tuberculosis drug candidate with the potential to replace current chemical-based drugs. However, more extensive toxicity, mechanism of action, and animal efficacy studies with clinical trials are needed.
Kim, Sukyung,Seo, Hoonhee,Mahmud, Hafij Al,Islam, Md Imtiazul,Lee, Byung-Eui,Cho, Myoung-Lae,Song, Ho-Yeon Elsevier 2018 Phytomedicine Vol.46 No.-
<P>Conclusions: Collinin extracted from the leaves of Z. schinifolium significantly inhibits the growth of MDR and XDR M. tuberculosis in the culture broth. In addition, it also inhibits the growth of intracellular drug-susceptible and drug-resistant tuberculosis in Raw264.7 and A549 cells. To our knowledge, this is the first report on the in vitro anti-tubercular activity of collinin, and our data suggest collinin as a potential drug to treat drug-resistant tuberculosis. Further studies are warranted to assess the in vivo efficacy and therapeutic potential of collinin.</P>
In Vitro Effect of DFC-2 on Mycolic Acid Biosynthesis in Mycobacterium tuberculosis
( Sukyung Kim ),( Hoonhee Seo ),( Hafij Al Mahmud ),( Md Imtiazul Islam ),( Yong-sik Kim ),( Jiwon Lyu ),( Kung-woo Nam ),( Byung-eui Lee ),( Kee-in Lee ),( Ho-yeon Song ) 한국미생물생명공학회(구 한국산업미생물학회) 2017 Journal of microbiology and biotechnology Vol.27 No.11
DFC-2, a methyl 5-[2-(dimethylamino)ethoxy]-7,12-dioxo-7,12-dihydrodinaphtho[1,2-b:2’,3’- d]furan-6-carboxylate, is reported to have antitubercular effects against Mycobacterium tuberculosis. At concentrations ranging from 0.19 to 0.39 μg/ml, DFC-2 inhibited both drugsusceptible and -resistant strains of M. tuberculosis. Microarray analyses were employed to gain insights into the molecular mechanisms of DFC-2’s action in M. tuberculosis. The most affected functional gene category was “lipid biosynthesis,” which is involved in mycolic acid synthesis. The decrease in transcription of genes related to mycolic acid synthesis was confirmed by RT-PCR. Furthermore, we found that DFC-2 triggered a reduction in mycolic acid levels, showing a similar pattern to that of mycolic acid synthesis inhibitor isoniazid. These results may explain how this compound kills mycobacteria efficiently by inhibiting mycolic acid synthesis.