Journal of Antibiotics最新文献

{"title":"Herbidomicins, two pairs of polyketide tautomers produced by an actinomycete of the genus Herbidospora","authors":"Feffiana M. Amin, Enjuro Harunari, Naoya Oku, Yasuhiro Igarashi","doi":"10.1038/s41429-024-00760-0","DOIUrl":"10.1038/s41429-024-00760-0","url":null,"abstract":"Herbidospora is one of the underexplored actinomycete genera from which only a limited number of secondary metabolites are reported. In our continuing investigation on less explored actinomycetes, a liquid culture of Herbidospora sp. RD 11066 was found to contain unknown metabolites that had no match in our in-house UV database. Chromatographic separation and following structural analysis using NMR and MS identified these metabolites to be chromanone and chromene derivatives, which were respectively composed of an inseparable mixture of two isomeric forms. The former polyketides, designated to be herbidomicins A1 (1) and A2 (2), are positional isomers in terms of a methyl substituent on an aromatic ring that mutually interconvert by acetal exchange by two phenolic hydroxy groups. The latter pair, herbidomicins B1 (3) and B2 (4), is Z/E-isomers regarding an enol ether double bond. Herbidomicins 1–4 were weakly antifungal against a dermatophytic fungus Trichophyton rubrum and were moderately cytotoxic against murine leukemia P388 cells.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 10","pages":"647-652"},"PeriodicalIF":2.1,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141581556","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":"Repurposing of dibucaine and niflumic acid as antimicrobial agents in combination with antibiotics against Staphylococcus aureus","authors":"Joydeep Chakraborty, Rittick Mondal, Jasmine Sultana, Saptak Banerjee, Amit Kumar Mandal, Hironmoy Sarkar","doi":"10.1038/s41429-024-00759-7","DOIUrl":"10.1038/s41429-024-00759-7","url":null,"abstract":"The versatile human commensal bacteria and pathogen Staphylococcus aureus cause several community and hospital-acquired illnesses associated with significant morbidity and death. Antibiotic therapy for S. aureus infections has grown increasingly difficult as the organism has developed a wide spectrum of antibiotic resistance mechanisms. This situation emphasizes the significance of developing and advocating new antimicrobials for preventative and therapeutic measures. Our study aimed to identify and evaluate new therapeutic options against S. aureus. We investigated the efficacy of two drugs, dibucaine, and niflumic acid, as potential adjuvant for anti-staphylococcal therapeutics. Dibucaine and niflumic acid found to have bactericidal activity against S. aureus. These drugs acted synergistically with antibiotics reducing the required dose of antibiotics up to 4 times. In combination with antibiotics, they were effectively and synergistically inhibited the formation of biofilms of S. aureus. The best synergistic partner of dibucaine was with kanamycin and tetracycline, whereas niflumic acid was with streptomycin and ampicillin. Both the drugs showed significant efflux inhibition in the bacteria. Moreover, the drugs are found to be safe at synergistic doses. Our findings suggest that dibucaine and niflumic acid could be potential adjuvant with antibiotics for the treatment of S. aureus infections. Their ability to significantly enhance the efficacy of antibiotics highlights their potential clinical significance as adjunct therapies.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 11","pages":"746-756"},"PeriodicalIF":2.1,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141536023","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":"Minimum inhibitory concentrations of aztreonam–avibactam, ceftazidime–avibactam and meropenem in clinical isolates of Klebsiella pneumoniae harboring carbapenemase genes","authors":"Vladimir Ageevets, Ofelia Sulian, Alisa Avdeeva, Polina Chulkova, Irina Ageevets, Vladimir Gostev, Kamilla Alieva, Maria Golikova, Sergey Sidorenko","doi":"10.1038/s41429-024-00758-8","DOIUrl":"10.1038/s41429-024-00758-8","url":null,"abstract":"This study was aimed at understanding the distributions of the MICs (minimum inhibitory concentrations) of aztreonam–avibactam, ceftazidime–avibactam and meropenem with respect to Klebsiella pneumoniae isolates producing different types of carbapenemases and their combinations. K. pneumoniae isolates were collected between 2019 and 2022 from 37 hospitals. PCR was used to screen for blaKPC-, blaNDM- and blaOXA-48-like genes. MICs were determined by the broth microdilution method for meropenem, aztreonam–avibactam and ceftazidime–avibactam at a constant avibactam concentration of 4 mg l−1. MIC distributions were analyzed for groups of isolates based on the identified carbapenemases including their combinations. The AZT/AVI MIC50 and MIC90 for all NDM-positive isolates were 0.25 and 0.5, respectively, and for serine-carbapenemase-only producers, they were 0.25 and 1 mg l−1, respectively. The CZD/AVI MIC50 and MIC90 values for serine-carbapenemase-only producers were 1 and 4 mg l−1, respectively. The AZT/AVI MIC50 and MIC90 values for co-producers and single carbapenemase producers were the same (i.e., 0.25 and 1 mg l−1, respectively). The total proportion of meropenem-susceptible isolates (≤8 mg l−1) among all the carbapenemase producers was 25.1% (31.1% among single-carbapenemase producers and 9.2% among co-producers). The results support the use of aztreonam–avibactam for the empirical treatment of infections caused by any carbapenemase producers.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 10","pages":"706-710"},"PeriodicalIF":2.1,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477996","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":"Actinoplanes kirromycinicus sp. nov., isolated from soil","authors":"Jiahao Zeng, Yohei Iizaka, Moriyuki Hamada, Aya Iwai, Riku Takeuchi, Atsushi Fukumoto, Tomohiko Tamura, Yojiro Anzai","doi":"10.1038/s41429-024-00756-w","DOIUrl":"10.1038/s41429-024-00756-w","url":null,"abstract":"A novel actinomycete, designated as TPMA0078T, was isolated from a soil sample collected in Shinjuku, Tokyo, Japan. 16S rRNA gene sequence analysis indicated that strain TPMA0078T belongs to the genus Actinoplanes and is closely related to Actinoplanes regularis IFO 12514T (99.86% 16S rRNA gene sequence similarity). The spores of strain TPMA0078T were motile, and the sporangia were cylindrical. The diamino acids in the cell wall peptidoglycan of strain TPMA0078T were meso-diaminopimelic acid and 3OH-meso-diaminopimelic acid. Whole-cell sugars were glucose and mannose, with galactose as a minor component. The major cellular fatty acids identified were iso-C15:0, iso-C16:0, and anteiso-C17:0. The predominant menaquinone was MK-9(H4), and the principal polar lipid was phosphatidylethanolamine. These chemotaxonomic properties of strain TPMA0078T were consistent with those of Actinoplanes. Meanwhile, digital DNA–DNA hybridization and average nucleotide identity values showed low relatedness between strain TPMA0078T and A. regularis NBRC 12514T. Furthermore, several phenotypic properties of strain TPMA0078T distinguished it from those of closely related species. Based on its genotypic and phenotypic characteristics, strain TPMA0078T represents a novel species of the genus Actinoplanes, for which the name Actinoplanes kirromycinicus sp. nov. is proposed. The type strain is TPMA0078T (=NBRC 116422T = TBRC 18262T).","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 10","pages":"657-664"},"PeriodicalIF":2.1,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41429-024-00756-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141460856","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":"Geministatins: new depside antibiotics from the fungus Austroacremonium gemini","authors":"Andrew Crombie, John A. Kalaitzis, Rachel Chen, Daniel Vuong, Alastair E. Lacey, Ernest Lacey, Roger G. Shivas, Yu Pei Tan, Nicolau Sbaraini, Yit-Heng Chooi, Andrew M. Piggott","doi":"10.1038/s41429-024-00755-x","DOIUrl":"10.1038/s41429-024-00755-x","url":null,"abstract":"Two new depside antibiotics, geministatins A (1) and B (2), were isolated from the fungus Austroacremonium gemini MST-FP2131 (Sordariomycetes, Ascomycota), which was recovered from rotting wood in the wet tropics of northern Australia. The structures of the geministatins were elucidated by detailed spectroscopic analysis, chemical degradation and comparison with literature values. Chemical degradation of 1 and 2 yielded three new analogues, geministatins C–E (3–5), as well as a previously reported compound dehydromerulinic acid A (6). Compounds 1, 2 and 6 exhibited antibacterial activity against the Gram-positive bacteria Bacillus subtilis (MIC 0.2–1.6 µg mL−1) and Staphylococcus aureus (MIC 0.78–6.3 µg mL−1), including methicillin-resistant S. aureus (MRSA), while 4 exhibited antifungal activity against the yeast Saccharomyces cerevisiae (MIC 13 µg mL−1).","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 10","pages":"639-646"},"PeriodicalIF":2.1,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41429-024-00755-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141460857","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 novel antistaphylococcal hit compounds","authors":"Galyna P. Volynets, Olga S. Iungin, Olga I. Gudzera, Hanna V. Vyshniakova, Mariia Yu. Rybak, Olena V. Moshynets, Anatoliy O. Balanda, Oleksiy V. Borovykov, Andrii O. Prykhod’ko, Sergiy S. Lukashov, Taras H. Maiula, Larysa V. Pletnova, Sergiy M. Yarmoluk, Michael A. Tukalo","doi":"10.1038/s41429-024-00752-0","DOIUrl":"10.1038/s41429-024-00752-0","url":null,"abstract":"Staphylococcus aureus is one of the most common nosocomial biofilm-forming pathogens worldwide that has developed resistance mechanisms against majority of the antibiotics. Therefore, the search of novel antistaphylococcal agents with unexploited mechanisms of action, especially with antibiofilm activity, is of great interest. Seryl-tRNA synthetase is recognized as a promising drug target for the development of antibacterials. We have carried out molecular docking of compounds with antistaphycoccal activity, which were earlier found by us using phenotypic screening, into synthetic site of S. aureus SerRS and found seven hit compounds with low inhibitory activity. Further, we have performed search of S. aureus SerRS inhibitors among compounds which were previously tested by us for inhibitory activity toward S. aureus ThrRS, that belong to the same class of aminoacyl-tRNA synthetases. Among them six hits were identified. We have selected four compounds for antibacterial study and found that the most active compound 1-methyl-3-(1H-imidazol-1-methyl-2-yl)-5-nitro-1H-indazole has MIC values toward S. aureus multidrug-resistant clinical isolates ranging from 78.12 to 156.2 µg/ml. However, this compound precipitated during anti-biofilm study. Therefore, we used 3-[N’-(2-hydroxy-3-methoxybenzylidene)hydrazino]-6-methyl-4H-[1,2,4]triazin-5-one with better solubility (ClogS value = 2.9) among investigated compounds toward SerRS for anti-biofilm study. It was found that this compound has a significant inhibitory effect on the growth of planktonic and biofilm culture of S. aureus 25923 with MIC value of 32 µg ml−1. At the same time, this compound does not reveal antibacterial activity toward Esherichia coli ATCC 47076. Therefore, this compound can be proposed as effective antiseptic toward multidrug-resistant biofilm-forming S. aureus isolates.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 10","pages":"665-678"},"PeriodicalIF":2.1,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141447649","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":"Synthesis and biochemical characterization of naphthoquinone derivatives targeting bacterial histidine kinases","authors":"Teruhiko Ishikawa, Yoko Eguchi, Masayuki Igarashi, Toshihide Okajima, Kohei Mita, Yuri Yamasaki, Kaho Sumikura, Taisei Okumura, Yuna Tabuchi, Chigusa Hayashi, Martina Pasqua, Marco Coluccia, Gianni Prosseda, Bianca Colonna, Chie Kohayakawa, Akiyoshi Tani, Jun-ichi Haruta, Ryutaro Utsumi","doi":"10.1038/s41429-024-00726-2","DOIUrl":"10.1038/s41429-024-00726-2","url":null,"abstract":"Waldiomycin is an inhibitor of histidine kinases (HKs). Although most HK inhibitors target the ATP-binding region, waldiomycin binds to the intracellular dimerization domain (DHp domain) with its naphthoquinone moiety presumed to interact with the conserved H-box region. To further develop inhibitors targeting the H-box, various 2-aminonaphthoquinones with cyclic, aliphatic, or aromatic amino groups and naphtho [2,3-d] isoxazole-4,9-diones were synthesized. These compounds were tested for their inhibitory activity (IC50) against WalK, an essential HK for Bacillus subtilis growth, and their minimum inhibitory concentrations (MIC) against B. subtilis. As a result, 11 novel HK inhibitors were obtained as naphthoquinone derivatives (IC50: 12.6–305 µM, MIC: 0.5–128 µg ml−1). The effect of representative compounds on the expression of WalK/WalR regulated genes in B. subtilis was investigated. Four naphthoquinone derivatives induced the expression of iseA (formerly yoeB), whose expression is negatively regulated by the WalK/WalR system. This suggests that these compounds inhibit WalK in B. subtilis cells, resulting in antibacterial activity. Affinity selection/mass spectrometry analysis was performed to identify whether these naphthoquinone derivatives interact with WalK in a manner similar to waldiomycin. Three compounds were found to competitively inhibit the binding of waldiomycin to WalK, suggesting that they bind to the H-box region conserved in HKs and inhibit HK activity.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 8","pages":"522-532"},"PeriodicalIF":2.1,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11284088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141452217","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":"Inhibition of the ATP synthase increases sensitivity of Escherichia coli carrying mcr-1 to polymyxin B","authors":"Zheng Fan, Zhoufei Li, Tongtong Fu, Yanling Feng, Yuchen Chen, Hongbo Liu, Bing Du, Xiaohu Cui, Hanqing Zhao, Guanhua Xue, Jinghua Cui, Chao Yan, Lin Gan, Junxia Feng, Ziying Xu, Zihui Yu, Jing Yuan","doi":"10.1038/s41429-024-00753-z","DOIUrl":"10.1038/s41429-024-00753-z","url":null,"abstract":"Bacterial infections caused by multidrug-resistant (MDR) gram-negative strains carrying the mobile colistin resistance gene mcr-1 are serious threats to world public health due to the lack of effective treatments. Inhibition of the ATP synthase makes bacteria such as Staphylococcus aureus and Klebsiella pneumoniae more sensitive to polymyxin. This provides new strategies for treating infections caused by polymyxins-resistant bacteria carrying mcr-1. Six mcr-1-positive strains were isolated from clinical samples, and all were identified as Escherichia coli. Here we investigated several ATP synthase inhibitors, N,N’-dicyclohexylcarbodiimide (DCCD), resveratrol, and piceatannol, for their antibacterial effects against the mcr-1-positive strains combined with polymyxin B (POL). Checkerboard assay, time-kill assay, biofilm inhibition and eradication assay indicated the significant synergistic effect of ATP synthase inhibitors/POL combination in vitro. Meanwhile, mouse infection model experiment was also performed, showing a 5 log10 reduction of the pathogen after treatment with the resveratrol/POL combination. Moreover, adding adenosine disodium triphosphate (Na2ATP) could inhibit the antibacterial effect of the ATP synthase inhibitors/POL combination. In conclusion, our study confirmed that inhibition of ATP production could increase the susceptibility of bacteria carrying mcr-1 to polymyxins. This provides a new strategy against polymyxins-resistant bacteria infection.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 10","pages":"685-696"},"PeriodicalIF":2.1,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141447650","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":"Two new aromatic tenvermectins from mutant Streptomyces avermitilis HU02-06","authors":"Hui Zhang, Zhen-yu Wang, Huan Qi, Shao-yong Zhang, Jun Huang, Ji-dong Wang, Wen-sheng Xiang","doi":"10.1038/s41429-024-00754-y","DOIUrl":"10.1038/s41429-024-00754-y","url":null,"abstract":"Two new aromatic tenvermectins (TVMs), 13-oleandrosyl-oleandrosyloxy ST906 (1) and aromatic TVM B (2), were isolated from the fermentation broth of Streptomyces avermitilis HU02-06. Their structures were established by extensive spectroscopic analysis, including 1D and 2D NMR and HRESIMS data. Bioassay test showed that these two new tenvermectins exhibited weak nematocidal activity against Bursaphelenchus xylophilus and moderate cytotoxic activity against tumor cell lines HepG2 and HCT116.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 10","pages":"653-656"},"PeriodicalIF":2.1,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141447651","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":"Ceftazidime is a potential drug to inhibit cell proliferation by increasing cellular p27","authors":"Tingting Zhang, Caixia Qiao, Yunshan Yang, Yukang Yuan, Zhenglan Zhao, Ying Miao, Qian Zhao, Renxia Zhang, Hui Zheng","doi":"10.1038/s41429-024-00751-1","DOIUrl":"10.1038/s41429-024-00751-1","url":null,"abstract":"The development of new therapeutic uses for existing drugs is important for the treatment of some diseases. Cephalosporin antibiotics stand as the most extensively utilized antibiotics in clinical practice, effectively combating bacterial infections. Here, we found that the antimicrobial drug ceftazidime strongly upregulates p27 protein levels by inhibiting p27 ubiquitination. The p27 protein is a classic negative regulator of the cell cycle. Next, we demonstrated that ceftazidime can impede the cell cycle from G1 to S phase, thus inhibiting cell proliferation. Furthermore, we found that ceftazidime promotes p27 expression and inhibits cell proliferation by reducing Skp2, which is a substrate recognition component of the Skp2-Cullin-F-box (SCF) ubiquitin ligase. Moreover, ceftazidime downregulates transcriptional expression of Skp2. Importantly, we demonstrated that ceftazidime inhibited the proliferation of tumor cells in vivo. These findings reveal ceftazidime-mediated inhibition of cell proliferation through the Skp2-p27 axis, and could provide a potential strategy for anti-tumor therapy.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 10","pages":"697-705"},"PeriodicalIF":2.1,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141428357","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}