Journal of Antibiotics最新文献

{"title":"Acknowledgments","authors":"Kazuro Shiomi","doi":"10.1038/s41429-024-00779-3","DOIUrl":"10.1038/s41429-024-00779-3","url":null,"abstract":"","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 12","pages":"783-785"},"PeriodicalIF":2.1,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41429-024-00779-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142714711","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":"Identification of nanaomycin A and its analogs by a newly established screening method for functional inhibitors of the type IX secretion system in Porphyromonas gingivalis.","authors":"Yuko Sasaki, Takehiro Matsuo, Yoshihiro Watanabe, Masato Iwatsuki, Yuki Inahashi, Satoshi Nishida, Mariko Naito, Mikio Shoji","doi":"10.1038/s41429-024-00790-8","DOIUrl":"https://doi.org/10.1038/s41429-024-00790-8","url":null,"abstract":"<p><p>Porphyromonas gingivalis, a Gram-negative anaerobic bacterium, is a key pathogen in chronic periodontitis. P. gingivalis has a type IX secretion system (T9SS) that secretes highly hydrolytic proteinases called gingipains for obtaining peptides as an energy source. Although most T9SS-related proteins have been identified, no specific inhibitor of T9SS has been reported. To screen T9SS inhibitors, we focused on and characterized a minimal liquid medium called mC medium that contains milk casein as the sole protein source. We found that P. gingivalis wild-type strain ATCC 33277 caused cloudiness of mC medium without growth. In mC medium, an alkylating agent, iodoacetamide (IAM) that is an inhibitor of gingipains, and a protonophore, carbonyl cyanide 3-chlorophenylhydrazone (CCCP) that dissipates the proton motive force required for T9SS-mediated secretion, clearly inhibited the increase in turbidity. Moreover, neither the gingipain-null mutant nor the T9SS-deficient mutant caused mC medium cloudiness, suggesting that mC medium cloudiness is dependent on gingipain activity and T9SS. These results indicated that mC medium can be used to assess P. gingivalis gingipain activity and its functional T9SS. Using an assay system with mC medium, we discovered that OM-173αA and OM-173βA in the Ōmura Natural Compound Library and nanaomycin A were probable T9SS inhibitors. The compounds need to be further investigated as tools for analyzing T9SS and as potential therapeutic agents for periodontal disease.</p>","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693525","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 new AMR drugs targeting modulators of antimicrobial activity using in vivo silkworm screening systems.","authors":"Fumiaki Tabuchi, Kazuhiro Mikami, Masanobu Miyauchi, Kazuhisa Sekimizu, Atsushi Miyashita","doi":"10.1038/s41429-024-00788-2","DOIUrl":"https://doi.org/10.1038/s41429-024-00788-2","url":null,"abstract":"<p><p>Global concerns about drug-resistant bacteria have underscored the need for new antimicrobial drugs. Emerging strategies in drug discovery include considering the third factors that influence drug activity. These factors include host-derived elements, adjuvants, and drug combinations, which are crucial in regulating antimicrobial efficacy. Traditional in vivo assessments have relied on animal models to study drug absorption, distribution, metabolism, excretion, and toxicity (ADMET). Alternative models, such as silkworms, are being explored to overcome the ethical and financial barriers associated with mammalian models. The silkworm has been proven effective in evaluating ADMET and in highlighting the therapeutic potential enhanced by third factors. Host factors (either mammalian or non-mammalian) enhance the antimicrobial activity of antimicrobial agents such as lysocin E. Additionally, using D-cycloserine to potentiate vancomycin has successfully combated vancomycin-resistant infections in silkworms. Leveraging silkworms in drug discovery could establish a novel screening method incorporating interactions with third factors, whether host related or non-host-related, thus promising new pathways for identifying antimicrobial drugs with unique mechanisms of action.</p>","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632972","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":"Structure-activity relationship studies of ME1111, a novel antifungal agent for topical treatment of onychomycosis.","authors":"Naomi Takei-Masuda, Maiko Iida, Makoto Ohyama, Kaori Kaneda, Kenji Ueda, Yuji Tabata","doi":"10.1038/s41429-024-00789-1","DOIUrl":"https://doi.org/10.1038/s41429-024-00789-1","url":null,"abstract":"<p><p>Onychomycosis is a prevalent disease in many areas of the world, affecting approximately 5.5% of the global population. Among several subtypes of onychomycosis, distal-lateral-subungual onychomycosis is the most common, and topical onychomycosis agents effective against this pathogenesis require properties such as high nail penetration and low affinity for keratin, the main component of the nail. To develop novel and highly effective antifungal agents with such properties, we first established an efficient ex vivo evaluation method using bovine hoof slices and human nails, and then used this method to screen an in-house compound library. Using this strategy, we identified 1, a structure with a phenyl-pyrazole skeleton. In subsequent analyses, we investigated the structure-activity relationship of 1, permitting the identification of 28 (Development Code ME1111).</p>","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632973","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":"Celludinone C, a new dihydroisobenzofuran isolated from Talaromyces cellulolyticus BF-0307.","authors":"Reiko Seki, Kenichiro Nagai, Keisuke Kobayashi, Satoru Shigeno, Tatsuya Shirahata, Yoshinori Kobayashi, Taichi Ohshiro, Hiroshi Tomoda","doi":"10.1038/s41429-024-00785-5","DOIUrl":"10.1038/s41429-024-00785-5","url":null,"abstract":"<p><p>Celludinones A and B, isolated from the fungus Talaromyces cellulolyticus BF-0307, were inhibitors of sterol O-acyltransferase (SOAT). Further searches for their congeners in the culture broth of the fungus by LC/UV and LC/MS analysis resulted in the discovery of four structurally related compounds, including a new dihydroisobenzofuran named celludinone C (1). The structure of 1, including its absolute stereochemistry, was elucidated by 1D/2D NMR and electronic circular dichroism (ECD) spectra. All of these compounds inhibited both SOAT1 and 2, with IC₅₀ values ranging from 8.5 to 30 µM.</p>","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632970","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":"Antimicrobial activity of α/β hybrid peptides incorporating tBu-β3,3Ac6c against methicillin-resistant Staphylococcus aureus","authors":"Aminur Rahman Sarkar,&nbsp;Jyoti Kumari,&nbsp;Arti Rathore,&nbsp;Rubina Chowdhary,&nbsp;Rakshit Manhas,&nbsp;Shifa Firdous,&nbsp;Avisek Mahapa,&nbsp;Rajkishor Rai","doi":"10.1038/s41429-024-00773-9","DOIUrl":"10.1038/s41429-024-00773-9","url":null,"abstract":"The incorporation of β-amino acids into peptides is a promising approach to develop proteolytically stable therapeutic agents. Short α/β hybrid peptides&nbsp;containing tBu-β3,3Ac6cː H2N-Lys-tBu-β3,3Ac6c-PEA, P1; H2N-Orn-tBu-β3,3Ac6c-PEA, P2; H2N-Arg-tBu-β3,3Ac6c-PEA, P3; LA-Lys-tBu-β3,3Ac6c-PEA, P4; LA-Orn-tBu-β3,3Ac6c-PEA, P5; LA-Arg-tBu-β3,3Ac6c-PEA, P6; LAu-Lys-tBu-β3,3Ac6c-PEA, P7; LAu-Orn-tBu-β3,3Ac6c-PEA, P8; and LAu-Arg-tBu-β3,3Ac6c-PEA, P9 were prepared. The antimicrobial efficacies of all the peptides were evaluated against ESKAPE pathogens, along with a small panel of multi-drug resistant (MDR) clinical isolates of S. aureus. Among all the peptides, P4, P6, and P7 showed significant efficacies against P. aeruginosa, S. aureus, and MRSA with an MIC value ranging from 6.25 to 12.5 μM. Further, in vitro, anti-staphylococcal assessment with their antimicrobial synergy of the peptides P4, P6, and P7 was carried out against MRSA, due to its better efficacy. The peptides P6 and P7 exhibited MRSA biofilm inhibition of 70% and 77%, respectively, at 4×MIC concentration. At its MIC concentration, about 19% hemolysis was observed for P4, P6, and P7.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 12","pages":"794-801"},"PeriodicalIF":2.1,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549004","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":"Thiazoplanomicin, a new thiazolyl peptide antibiotic from the leaf-litter actinomycete Actinoplanes sp. MM794L-181F6.","authors":"Yasuhiro Takehana, Hideyuki Muramatsu, Masaki Hatano, Yoshimasa Ishizaki, Maya Umekita, Yuko Shibuya, Chigusa Hayashi, Tomoyuki Kimura, Toshifumi Takeuchi, Ken Shimuta, Ryuichi Sawa, Masayuki Igarashi","doi":"10.1038/s41429-024-00783-7","DOIUrl":"https://doi.org/10.1038/s41429-024-00783-7","url":null,"abstract":"<p><p>A new bioactive substance was identified from a leaf-litter actinomycete strain by screening for antibacterial activity against Neisseria gonorrhoeae. The thiazolyl peptide antibiotic, named thiazoplanomicin, was isolated from the secondary metabolites of the leaf-litter actinomycetes Actinoplanes sp. MM794L-181F6 by extraction with n-butanol, silica gel column chromatography, Sephadex LH-20 column chromatography, and preparative HPLC. Thiazoplanomicin was characterized by LC-HR-ESI-MS, NMR, and X-ray analyses, along with analysis of the degradation products and chemical derivatives, and determined to be a nocathiacin-like multiple macrocyclic thiazolyl peptide. Thiazoplanomicin showed potent antimicrobial activity against gonococcal strains, including those resistant to known anti-gonococcal compounds such as telithromycin, azithromycin, and ceftriaxone, with MIC values ranging from 0.0312 to 0.125 µg ml^-1. Such anti-gonococcal activity has not been reported on nocathiacin-like thiazolyl peptide antibiotic so far. Similar to other thiazolyl peptide antibiotics, thiazoplanomicin also showed potent antibacterial activity against Gram-positive bacteria with MIC values ranging from 0.0005 to 0.0156 µg ml^-1 but showed no antibacterial activity against Escherichia coli.</p>","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142523721","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":"Sinulariapeptide F, a new peptide from culture broth of marine-derived fungus Simplicillium sp. SCSIO 41222.","authors":"Yan-Chun He, Meng-Qin Wang, Qing-Qing Tie, Xiao-Wen Huang, Yong-Hong Liu, Yun-Qiu Li, Bin Yang","doi":"10.1038/s41429-024-00780-w","DOIUrl":"https://doi.org/10.1038/s41429-024-00780-w","url":null,"abstract":"<p><p>One new compound named sinulariapeptide F (1) together with one known butyrolactone (2) and seven known peptides (3-9) were isolated from the fungus Simplicillium sp. SCSIO 41222. Their structures and absolute configurations were established using HRESIMS, NMR spectroscopy (¹H, ¹³C, HSQC, HMBC) and marfey's method. All of these compounds were assessed their inhibitory activity of acetylcholinesterase (AChE) and pancreatic lipase (PL). Compounds 4 and 6 were selected to test for the inhibitory activity against programmed cell death-1 (PD-1)/ programmed cell death-ligand 1 (PD-L1). The results indicated that compound 4 displayed potent inhibition activity against PD-1/ PD-L1 with an IC₅₀ value of 0.656 μM. Furthermore, the docking analysis demonstrated the interactions between 4 and proteins, suggesting PD-L1 to be a probable target for compound 4.</p>","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142513233","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":"Streptomyces yaizuensis sp. nov., a berninamycin C-producing actinomycete isolated from sponge.","authors":"Miku Takahashi, Kanata Hoshino, Moriyuki Hamada, Tomohiko Tamura, Ryota Moriuchi, Hideo Dohra, Youji Nakagawa, Susumu Kokubo, Motoyuki Yamazaki, Hiroyuki Nakagawa, Masayuki Hayakawa, Shinya Kodani, Hideki Yamamura","doi":"10.1038/s41429-024-00782-8","DOIUrl":"https://doi.org/10.1038/s41429-024-00782-8","url":null,"abstract":"<p><p>While screening for antibiotics in a marine sample, we discovered a berninamycin C-producing actinomycete, designated YSPA8^T, isolated from a sponge. A polyphasic approach was used to determine the taxonomic position of the strain. Strain YSPA8^T formed sympodially branched aerial mycelia that ultimately segment into chains of spores. Comparative and phylogenetic analyses of the 16S rRNA gene sequence showed that strain YSPA8^T were closely related to Streptomyces clavuligerus ATCC 27064^T (99.66%), Streptomyces amakusaensis NRRL B-3351^T (98.69%), Streptomyces inusitatus NBRC 13601^T (98.48%), and 'Streptomyces jumonjinensis' JCM 4947 (98.41%). The phylogenetic tree using the 16S rRNA gene sequences, and both phylogenomic trees suggested that the closest relative of strain YSPA8^T was S. clavuligerus ATCC 27064^T. The average nucleotide identity, digital DNA-DNA hybridization, and average amino acid identity values between strain YSPA8^T and S. clavuligerus ATCC 27064^T were 84.1%, 28.9%, and 82.5%, respectively, which were below the thresholds of 95%, 70%, and 95% for a prokaryotic conspecific assignment. The G + C of the strain YSPA8^T was 72.6%. Whole-cell hydrolysates of strain YSPA8^T contained LL-diaminopimelic acid. The predominant menaquinones were MK-9(H₆) (49%) and MK-9(H₈) (48%), and the major fatty acids were C_16:0 (26.8%), C_16:1 ω7c/ω6c (17.2%), iso-C_16:0 (16.0%), and iso-C_15:0 (12.5%). The major phospholipids were diphosphatidylglycerol, phosphatidylethanolamine, and other unidentified phospholipids. Based on the phenotypic, phylogenetic, genomic, and chemotaxonomic data, strain YSPA8^T represents a novel species of the genus Streptomyces, and the proposed name for this species is Streptomyces yaizuensis sp. nov. The type strain is YSPA8^T (=NBRC 115866^T = TBRC 17196^T).</p>","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142513234","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":"Resistance to linezolid in Staphylococcus aureus by mutation, modification, and acquisition of genes.","authors":"Wenjing Yang, Taoran Chen, Qi Zhou, Jiancheng Xu","doi":"10.1038/s41429-024-00778-4","DOIUrl":"https://doi.org/10.1038/s41429-024-00778-4","url":null,"abstract":"<p><p>Linezolid binds to the 50S subunit of the bacterial ribosome, inhibiting bacterial protein synthesis by preventing the formation of the initiation complex. Oxazolidinone antimicrobial drugs represent the last line of defense in treating Staphylococcus aureus infections; thus, resistance to linezolid in S. aureus warrants high priority. This article examines the major mechanisms of resistance to linezolid in S. aureus, which include: mutations in the domain V of 23S rRNA (primarily G2576); chromosomal mutations in the rplC, rplD, and rplV genes (encoding the ribosomal uL3, uL4, and uL22 proteins, respectively); the exogenous acquisition of the methylase encoded by the chloramphenicol-florfenicol resistance (cfr) gene; the endogenous methylation or demethylation of 23S rRNA; the acquisition of optrA and poxtA resistance genes; and the existence of the LmrS multidrug efflux pump. In conclusion, these mechanisms mediate resistance through mutations or modifications to the bacterial target, thereby reducing the affinity of linezolid for the peptidyl transferase center (PTC) binding site or by preventing the binding of linezolid to the PTC through a ribosomal protective effect. The existence of additional, unexplained resistance mechanisms requires further investigation and verification.</p>","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142481209","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}