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( Md Imtiazul Islam ),( Hoonhee Seo ),( Asma Redwan ),( Sukyung Kim ),( Saebim Lee ),( Mashuk Siddiquee ),( Ho-yeon Song ) 한국미생물 · 생명공학회 2022 Journal of microbiology and biotechnology Vol.32 No.1
Clostridioides difficile infection (CDI) is a significant cause of hospital-acquired and antibiotic-mediated intestinal diseases and is a growing global public health concern. Overuse of antibiotics and their effect on normal intestinal flora has increased the incidence and severity of infections. Thus, the development of new, effective, and safe treatment options is a high priority. Here, we report a new probiotic strain, Bacillus amyloliquefaciens (BA PMC-80), and its in vitro/in vivo anti-C. difficile effect as a prospective novel candidate for replacing conventional antibiotics. BA PMC-80 showed a significant anti-C. difficile effect in coculture assay, and its cell-free supernatant (CFS) also exhibited a considerable anti-C. difficile effect with an 89.06 μg/ml 50% minimal inhibitory concentration (MIC) in broth microdilution assay. The CFS was stable and equally functional under different pHs, heat, and proteinase treatments. It also exhibited a high sensitivity against current antibiotics and no toxicity in subchronic toxicity testing in hamsters. Finally, BA PMC-80 showed a moderate effect in a hamster CDI model with reduced infection severity and delayed death. However, further studies are required to optimize the treatment condition of the hamster CDI model for better efficacy and identify the antimicrobial compound produced by BA PMC-80.
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.
( 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.
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>