Haeun Kwon, Hee Woon Ann, Sojung Park, Jaeyoung Kwon, Keunwan Park, Seung Mok Ryu, Yuanqiang Guo, Jae-Jin Kim, Joung Han Yim, Il-Chan Kim, Sang Hee Shim, Sullim Lee, Dongho Lee
{"title":"Mass spectrometry-guided isolation of thiodiketopiperazines from an EtOAc-extract of Setosphaeria rostrata culture medium and their anti-skin aging effects on TNF-α-induced human dermal fibroblasts","authors":"Haeun Kwon, Hee Woon Ann, Sojung Park, Jaeyoung Kwon, Keunwan Park, Seung Mok Ryu, Yuanqiang Guo, Jae-Jin Kim, Joung Han Yim, Il-Chan Kim, Sang Hee Shim, Sullim Lee, Dongho Lee","doi":"10.1038/s41429-023-00702-2","DOIUrl":"10.1038/s41429-023-00702-2","url":null,"abstract":"Using mass spectrometry (MS)-guided isolation methods, a new thiodiketopiperazine derivative (1) and exserohilone (2) were isolated from an EtOAc-extract of Setosphaeria rostrata culture medium. The chemical structure of the new compound was elucidated by MS and NMR spectroscopy, and the absolute configurations were established by the quantum mechanical calculations of electronic circular dichroism. All isolated compounds were examined for their effects on reactive oxygen species (ROS) production, matrix metalloproteinase 1 (MMP-1) secretion, and procollagen type I α1 secretion in tumor necrosis factor (TNF)-α-induced human dermal fibroblasts. Compound 1 and exserohilone (2) exhibited the inhibition of TNF-α-induced ROS generation and MMP-1 secretion. Additionally, compound 1 and exserohilone (2) increased the procollagen type I α1 secretion. Compound 1 docked computationally into the active site of MMP-1 (−6.0 kcal/mol).","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 4","pages":"257-263"},"PeriodicalIF":3.3,"publicationDate":"2024-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139500738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hannah J. T. Nonarath, Michael A. Jackson, Renee M. Penoske, Thomas C. Zahrt, Neil P. J. Price, Brian A. Link
{"title":"The tunicamycin derivative TunR2 exhibits potent antibiotic properties with low toxicity in an in vivo Mycobacterium marinum-zebrafish TB infection model","authors":"Hannah J. T. Nonarath, Michael A. Jackson, Renee M. Penoske, Thomas C. Zahrt, Neil P. J. Price, Brian A. Link","doi":"10.1038/s41429-023-00694-z","DOIUrl":"10.1038/s41429-023-00694-z","url":null,"abstract":"Tunicamycins (TUN) are well-defined, Streptomyces-derived natural products that inhibit protein N-glycosylation in eukaryotes, and by a conserved mechanism also block bacterial cell wall biosynthesis. TUN inhibits the polyprenylphosphate-N-acetyl-hexosamine-1-phospho-transferases (PNPT), an essential family of enzymes found in both bacteria and eukaryotes. We have previously published the development of chemically modified TUN, called TunR1 and TunR2, that have considerably reduced activity on eukaryotes but that retain the potent antibacterial properties. A mechanism for this reduced toxicity has also been reported. TunR1 and TunR2 have been tested against mammalian cell lines in culture and against live insect cells but, until now, no in vivo evaluation has been undertaken for vertebrates. In the current work, TUN, TunR1, and TunR2 are investigated for their relative toxicity and antimycobacterial activity in zebrafish using a well-established Mycobacterium marinum (M. marinum) infection system, a model for studying human Mycobacterium tuberculosis infections. We also report the relative ability to activate the unfolded protein response (UPR), the known mechanism for the eukaryotic toxicity observed with TUN treatment. Importantly, TunR1 and TunR2 retained their antimicrobial properties, as evidenced by a reduction in M. marinum bacterial burden, compared to DMSO-treated zebrafish. In summary, findings from this study highlight the characteristics of recently developed TUN derivatives, mainly TunR2, and its potential for use as a novel anti-bacterial agent for veterinary and potential medical purposes.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 4","pages":"245-256"},"PeriodicalIF":3.3,"publicationDate":"2024-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41429-023-00694-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139492841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Design, biological characteristics, and antibacterial mechanism of high therapeutic index antimicrobial peptides with PRRP as central axis","authors":"Shuang Yu, Boyan Jia, Ying Zhang, Yue Yu, Zhihua Pei, Hongxia Ma","doi":"10.1038/s41429-023-00697-w","DOIUrl":"10.1038/s41429-023-00697-w","url":null,"abstract":"As the important components of biological innate immunity, antimicrobial peptides (AMPs) were found in a variety of organisms including insects, plants, animals, bacteria, fungi, etc. However, high hemolytic activity, high toxicity, and poor stability of natural AMPs hinder serious their application as therapeutic agents. To overcome these problems, in this study we use PRRP as a central axis, and peptides were designed based on the sequence template XRRXXRXPRRPXRXXRRX-NH2, where X represents a hydrophobic amino acid like Phe (F), Ile (I), Val (V), and Leu (L). The designed peptides LR18, FR18, and IR18 showed effective antimicrobial activity against some Gram-positive bacteria and Gram-negative bacteria, low cytotoxicity to mammalian cells, and had a tendency to form α-helical structures in membrane-mimetic environments. Among them, peptide LR18 (X: L) showed the highest geometric mean average treatment index (GMTI = 42.7) against Gram-negative bacteria, and FR18 (X: L) showed the highest GMTI (22.86) against Gram-positive bacteria. LR18 and FR18 also showed better salt, temperature, pH, and trypsin stability. LR18 and FR18 exert their antimicrobial effects mainly through destroying bacteria cell membrane. Briefly, peptide LR18 and FR18 have the potential to serve as a therapeutic agent to reduce antibiotic resistance owing to its high therapeutic index and great stability.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 3","pages":"170-181"},"PeriodicalIF":3.3,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139482664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jun Li, Zhenye Yang, Chuanling Shi, Xiaoyun Wu, Le Zhou, Yongqian Liang, Qinglian Li, Jianhua Ju
{"title":"Semi-synthesis and structure-activity relationship study yield antibacterial vicenistatin derivatives with low cytotoxicity","authors":"Jun Li, Zhenye Yang, Chuanling Shi, Xiaoyun Wu, Le Zhou, Yongqian Liang, Qinglian Li, Jianhua Ju","doi":"10.1038/s41429-023-00701-3","DOIUrl":"10.1038/s41429-023-00701-3","url":null,"abstract":"Vicenistatin (1) is a 20-membered polyketide macrocyclic antibiotic with potent antimicrobial and cytotoxic activities. In this study, to further explore the potential of 1 as candidates of antibacterial drug development, 4’-N-demethyl vicenistatin (2), a secondary metabolite obtained from the ∆vicG mutant strain of Monodonata labio-associated Streptomyces parvus SCSIO Mla-L010, was utilized as a starting material for modifications of 4’-amino group of vicenistatin. Six new vicenistatin derivatives (3–8) were semi-synthesized through a concise route of amino modification with various aliphatic and aromatic aldehydes. Our study reveals that the bioactivity of vicenistatin is closely related to amino modification in sugar moiety, which results from the length of alkyl side chain as well as the presence of electron withdrawing/denoting group on the benzene ring. Importantly, compounds 4 with a butyl group and 8 with a 3,5-dihydroxyl-benzyl group at 4’-amino group, respectively, exhibited good antimicrobial activities, with MIC values spanning 0.5–4 μg ml−1 to Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, Micrococcus luteus and Bacillus subtilis, with low cytotoxicity. This research promotes the further exploration of structure-activity relationships of vicenistatin and provides new vicenistatin derivatives for development of future anti-infectious agents with reduced cytotoxicity.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 4","pages":"221-227"},"PeriodicalIF":3.3,"publicationDate":"2024-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139474951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Antifungal profile against Candida auris clinical isolates of tyroscherin and its new analog produced by the deep-sea-derived fungal strain Scedosporium apiospermum FKJ-0499","authors":"Haruki Azami, Yoshihiro Watanabe, Kazunari Sakai, Hiroki Nakahara, Hiroki Kojima, Toshiyuki Tokiwa, Kenichi Nonaka, Yoshihiko Noguchi, Yuriko Nagano, Tomoyasu Hirose, Toshiaki Sunazuka, Hidehito Matsui, Naoaki Arima, Kazutoyo Abe, Hideaki Hanaki, Masato Iwatsuki","doi":"10.1038/s41429-023-00696-x","DOIUrl":"10.1038/s41429-023-00696-x","url":null,"abstract":"A new antifungal compound, named N-demethyltyroscherin (1), was discovered from the static fungal cultured material of Scedosporium apiospermum FKJ-0499 isolated from a deep-sea sediment sample together with a known compound, tyroscherin (2). The structure of 1 was elucidated as a new analog of 2 by MS and NMR analyses. The absolute configuration of 1 was determined by chemical derivatization. Both compounds showed potent in vitro antifungal activity against clinically isolated Candida auris strains, with MIC values ranging from 0.0625 to 4 µg ml–1.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 3","pages":"156-162"},"PeriodicalIF":3.3,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139418647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Di Mao, Pengwei Yu, Naoya Shinzato, Lei Zhang, Weiping Zheng, Shan Lu, Hideaki Kakeya
{"title":"Precezomycin, a novel antibiotic biosynthetic precursor of cezomycin, from actinomycete Kitasatospora putterlickiae 10–13","authors":"Di Mao, Pengwei Yu, Naoya Shinzato, Lei Zhang, Weiping Zheng, Shan Lu, Hideaki Kakeya","doi":"10.1038/s41429-023-00695-y","DOIUrl":"10.1038/s41429-023-00695-y","url":null,"abstract":"A novel antibiotic biosynthetic precursor of cezomycin, named precezomycin (1), was isolated from culture broth of actinomycete Kitasatospora putterlickiae 10–13. The planar structure was determined by 1D/2D NMR and HR(ESI)MS data analyses, and the absolute configurations were established by TDDFT calculation of ECD spectra. Precezomycin (1) exhibited moderate antibacterial activity against gram-positive bacteria including Staphylococcus aureus and Bacillus subtilis. The discovery of 1 extends the natural product family of cezomycin and provides a new insight into understanding the biosynthetic process of these polyether ionophore metabolites.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 3","pages":"189-192"},"PeriodicalIF":3.3,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139410854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Identification of a new oligomycin derivative as a specific inhibitor of the alternative peptidoglycan biosynthetic pathway","authors":"Shuhei Umetsu, Takeshi Tsunoda, Haruka Kiyanagi, Yuki Inahashi, Kenichi Nonaka, Tohru Dairi, Yasushi Ogasawara","doi":"10.1038/s41429-023-00693-0","DOIUrl":"10.1038/s41429-023-00693-0","url":null,"abstract":"Peptidoglycan is an important macromolecule in bacterial cell walls to maintain cell integrity, and its biosynthetic pathway has been well studied. Recently, we demonstrated that some bacteria such as Xanthomonas oryzae, a pathogen causing bacterial blight of rice, used an alternative pathway for peptidoglycan biosynthesis. In this pathway, MurD2, a MurD homolog, catalyzed the attachment of l-Glu to UDP-MurNAc-l-Ala and MurL, which did not show homology to any known protein, catalyzed epimerization of the terminal l-Glu of the MurD2 product to generate UDP-MurNAc-l-Ala-d-Glu. Because the alternative pathway also operates in some other plant pathogens and opportunistic pathogens, specific inhibitors of the alternative pathway could function as pesticides and antibiotics for these pathogens. In this study, we searched for specific inhibitors of the alternative pathway from metabolites produced by actinomycetes and identified a new oligomycin-class polyketide, which was revealed to inhibit the MurD2 reaction, in culture broth of Micromonospora sp. K18-0097.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 3","pages":"182-184"},"PeriodicalIF":3.3,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41429-023-00693-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139418648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The potentiation activity of β-lactam by phomoidrides and oxasetin against methicillin-resistant Staphylococcus aureus","authors":"Masako Honsho, Aoi Kimishima, Akari Ikeda, Masato Iwatsuki, Kenichi Nonaka, Hidehito Matsui, Hideaki Hanaki, Yukihiro Asami, Toshiaki Sunazuka","doi":"10.1038/s41429-023-00691-2","DOIUrl":"10.1038/s41429-023-00691-2","url":null,"abstract":"Antimicrobial resistance (AMR) causes a global health threat and enormous damage for humans. Among them, Methicillin-resistant Staphylococcus aureus (MRSA) resistant to first-line therapeutic β-lactam drugs such as meropenem (MEPM) is problematic. Therefore, we focus on combination drug therapy and have been seeking new potentiators of MEPM to combat MRSA. In this paper, we report the isolation of phomoidrides A–D and its new analog, phomoidride H along with a polyketide compound, oxasetin from the culture broth of Neovaginatispora clematidis FKI-8547 strain as potentiators of MEPM against MRSA.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 3","pages":"185-188"},"PeriodicalIF":3.3,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139093803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Le Wang, Yao Xiao, Wenxin Lai, Ru Jia, Qinglin Deng, Xin Wang, Hongqiu Shi, Yiwen Yang, Binghuo Zhang
{"title":"Micrococcus lacusdianchii sp. nov., an attached bacterium inhibited by metabolites from its symbiotic algae","authors":"Le Wang, Yao Xiao, Wenxin Lai, Ru Jia, Qinglin Deng, Xin Wang, Hongqiu Shi, Yiwen Yang, Binghuo Zhang","doi":"10.1038/s41429-023-00690-3","DOIUrl":"10.1038/s41429-023-00690-3","url":null,"abstract":"A novel actinobacterial strain, designated as JXJ CY 30 T, was isolated from the phycosphere of Microcystis aeruginosa FACHB-905 (Maf) collected from Lake Dianchi, China. The strain was a Gram-stain-positive, aerobic and coccus-shaped actinobacterium. It had alanine, glutamic acid, aspartic acid, and lysine in the peptidoglycan, and mannose, ribose and arabinose in its cell wall sugars, anteiso-C15:0 and iso-C15:0 as the main cellular fatty acids, MK-7 and MK-8 as the major respiratory quinones, and phosphatidylglycerol, diphosphatidylglycerol, phosphatidylinositol, glycolipid, and an unidentified phospholipid as the polar lipids. The DNA G + C content was 73.08%. Its 16 S rRNA gene sequence shared 99.14%, and 98.75% similarities with Micrococcus flavus DSM 19079 T and M. porci KD337-16T, respectively, and ≤98.41% similarities with other type strains of the genus Micrococcus. It formed independent clade with M. flavus DSM 19079 T on the phylogenetic trees. The digital DNA-DNA hybridization and average nucleotide identity values between strain JXJ CY 30 T and M. flavus DSM 19079 T and M. porci KD337-16T were 48.0% and 92.1%, 25.5% and 83.2%, respectively. These data above indicated that strain JXJ CY 30 T represented a new species of the genus Micrococcus, and the species epithet is proposed as Micrococcus lacusdianchii sp. nov. (type strain JXJ CY 30 T = KCTC 49378 T = CGMCC 1.17508 T). Strain JXJ CY 30 T can potentially provide Maf with various nutrients such as available phosphorus and nitrogen, plant hormones, various vitamins and carotenoids for growth, while it was inhibited by metabolites from its symbiotic algae Maf.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 3","pages":"163-169"},"PeriodicalIF":3.3,"publicationDate":"2023-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139040950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Discovery of antifungal secondary metabolites from an intestinal fungus Fusarium sp.","authors":"Mingkai Zhang, Baosong Chen, Huanqin Dai, Jingzu Sun, Hongwei Liu, Junjie Han","doi":"10.1038/s41429-023-00692-1","DOIUrl":"10.1038/s41429-023-00692-1","url":null,"abstract":"Intestinal fungi, which are important parts of the gut microbiota, have the ability to produce specialized metabolites that significantly contribute to maintaining the balance of the gut microbiota and promoting the health of the host organism. In the present study, two new glycosides, including fusintespyrone A (1) and cerevisterolside A (4), as well as ten known compounds were isolated from the intestinal fungus Fusarium sp. LE06. The structures of the new compounds were elucidated by a combination of spectroscopic methods, such as mass spectrometry (MS) and nuclear magnetic resonance (NMR), along with chemical reactions and calculations of NMR and ECD spectra. Compounds 1–3 showed significant growth inhibition against Aspergillus fumigatus, Fusarium oxysporum, and Verticillium dahliae with MIC values in the range of 1.56–6.25 μg ml−1.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 3","pages":"193-198"},"PeriodicalIF":3.3,"publicationDate":"2023-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139040949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}