Pub Date : 2025-04-07DOI: 10.1038/s41429-025-00819-6
Takayoshi Awakawa
As research into the biosynthesis of natural products has matured, the biosynthetic pathways of common skeletons have been identified one after another, and attention is now being focused on research into the biosynthetic machineries of compounds with rare skeletons. Such research has the potential for leading to the discovery of new biosynthetic enzymes and artificial biosynthesis of unnatural compounds. In this study, I introduce the biosynthetic research on altemicidin, SB-203207, and SB-203208, which are rare natural products containing sulfonamide and azaindane skeletons. Further, self-resistance gene mining, the biosynthetic machineries of aminoacyl transferases, the synthesis of sulfonamides and azaindanes, and the structural basis and reaction mechanism of the biosynthetic enzyme SzbP, which uses beta-nicotinamide adenine dinucleotide (β-NAD) and S-adenosylmethionine (SAM) as substrates to create the first intermediate in the biosynthesis, are discussed in detail.
{"title":"Biosynthesis of antibiotics with sulfonamide and azaindane moieties","authors":"Takayoshi Awakawa","doi":"10.1038/s41429-025-00819-6","DOIUrl":"10.1038/s41429-025-00819-6","url":null,"abstract":"As research into the biosynthesis of natural products has matured, the biosynthetic pathways of common skeletons have been identified one after another, and attention is now being focused on research into the biosynthetic machineries of compounds with rare skeletons. Such research has the potential for leading to the discovery of new biosynthetic enzymes and artificial biosynthesis of unnatural compounds. In this study, I introduce the biosynthetic research on altemicidin, SB-203207, and SB-203208, which are rare natural products containing sulfonamide and azaindane skeletons. Further, self-resistance gene mining, the biosynthetic machineries of aminoacyl transferases, the synthesis of sulfonamides and azaindanes, and the structural basis and reaction mechanism of the biosynthetic enzyme SzbP, which uses beta-nicotinamide adenine dinucleotide (β-NAD) and S-adenosylmethionine (SAM) as substrates to create the first intermediate in the biosynthesis, are discussed in detail.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"78 6","pages":"341-349"},"PeriodicalIF":2.7,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143804890","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}
Pub Date : 2025-03-31DOI: 10.1038/s41429-025-00816-9
Hanxiang Jiang, Jiangfeng Qi, Jiwen Wang, Jiaqin Chen, Dong Feng, Junbiao Yang, Xinna Liu, Mengqun Liu, Xvzhe Zhou, Zhilong An, Yuanyuan Lu, Chun Ge, Ying Wang
Acetobacter baumannii poses escalating clinical challenges due to its exceptional adaptability, demanding innovative antimicrobial strategies. This study pioneers an investigation into the antibacterial efficacy and molecular mechanism of Terramide A, a hydroxamate siderophore isolated from Aspergillus terreus, against notorious A. baumannii. Employing a multidisciplinary approach integrating phenotypic characterization with mechanistic interrogation, we demonstrate that Terramide A exerts significant inhibitory effects against A. baumannii and P. aeruginosa, pathogens critically dependent on siderophore-mediated iron acquisition for survival and virulence. Structural characterization underlines the hydroxamate moieties of Terramide A presumably supports its hypothesized role as a fungal siderophore, involving competitive iron sequestration and bacterial homeostasis. Subsequently, multi-omics investigation of susceptible strain AB19606 delineated a metabolic collapse cascade due to iron acquisition competition: (1) impairment of central metabolism and energy production through oxidative phosphorylation (OXPHO) inhibitions; (2) compromised stress adaptation and bacterial flexibility; (3) compensatory overactivation of siderophores biosynthesis and transportation, depleting metabolic intermediates and exacerbating stress; (4) coordinated suppression of virulence determinants, such as secretory systems and biofilm formation. These molecular derangements translated into phenotypic deficits, including quorum sensing, diminished autoinducer peptides production, and morphological/functional abnormalities. In vivo evaluation in a rat skin wound infection model further demonstrated that Terramide A promotes wound healing and mitigates inflammation, supporting its antibacterial efficacy. These findings establish Terramide A as a promising antibacterial agent and provide critical insights into iron-competitive antimicrobial strategies to exploit micro-nutrient deprivation and metabolic dysfunction. However, further research is needed to optimize the siderophore-based scaffold, clarify its mechanisms, and assess therapeutic potential.
{"title":"Terramide A: a novel ironophore targeting Acinetobacter baumannii with mechanistic insights into bacterial iron deprivation","authors":"Hanxiang Jiang, Jiangfeng Qi, Jiwen Wang, Jiaqin Chen, Dong Feng, Junbiao Yang, Xinna Liu, Mengqun Liu, Xvzhe Zhou, Zhilong An, Yuanyuan Lu, Chun Ge, Ying Wang","doi":"10.1038/s41429-025-00816-9","DOIUrl":"10.1038/s41429-025-00816-9","url":null,"abstract":"Acetobacter baumannii poses escalating clinical challenges due to its exceptional adaptability, demanding innovative antimicrobial strategies. This study pioneers an investigation into the antibacterial efficacy and molecular mechanism of Terramide A, a hydroxamate siderophore isolated from Aspergillus terreus, against notorious A. baumannii. Employing a multidisciplinary approach integrating phenotypic characterization with mechanistic interrogation, we demonstrate that Terramide A exerts significant inhibitory effects against A. baumannii and P. aeruginosa, pathogens critically dependent on siderophore-mediated iron acquisition for survival and virulence. Structural characterization underlines the hydroxamate moieties of Terramide A presumably supports its hypothesized role as a fungal siderophore, involving competitive iron sequestration and bacterial homeostasis. Subsequently, multi-omics investigation of susceptible strain AB19606 delineated a metabolic collapse cascade due to iron acquisition competition: (1) impairment of central metabolism and energy production through oxidative phosphorylation (OXPHO) inhibitions; (2) compromised stress adaptation and bacterial flexibility; (3) compensatory overactivation of siderophores biosynthesis and transportation, depleting metabolic intermediates and exacerbating stress; (4) coordinated suppression of virulence determinants, such as secretory systems and biofilm formation. These molecular derangements translated into phenotypic deficits, including quorum sensing, diminished autoinducer peptides production, and morphological/functional abnormalities. In vivo evaluation in a rat skin wound infection model further demonstrated that Terramide A promotes wound healing and mitigates inflammation, supporting its antibacterial efficacy. These findings establish Terramide A as a promising antibacterial agent and provide critical insights into iron-competitive antimicrobial strategies to exploit micro-nutrient deprivation and metabolic dysfunction. However, further research is needed to optimize the siderophore-based scaffold, clarify its mechanisms, and assess therapeutic potential.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"78 5","pages":"295-313"},"PeriodicalIF":2.7,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756026","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}
Sporogen-AO1, a sporulation-promoting substance of Aspergillus oryzae was found to be a nonspecific translation inhibitor during screening of 22400 compounds. Sporogen-AO1 inhibited protein synthesis in cell-free protein synthesis (CFPS) systems derived from HeLa cell, wheat germ and yeast extracts, but not from E. coli S30 extracts. Sporogen-AO1 inhibited translation initiated from the cricket paralysis virus internal ribosome entry site, which does not require any translation initiation factor. Inhibition of translation due to sporogen-AO1was also observed in a CFPS system reconstituted with human translation factors and ribosomes; sporogen-AO1 decreased translation in the reconstituted CFPS system lacking aminoacyl-tRNA synthetases or translation termination factors. Thus, sporogen-AO1 targets the translation elongation phase comprising the ribosome and translation elongation factors. The IC50 values of sporogen-AO1 and cycloheximide were 7.44 ± 1.63 μM and 0.17 ± 0.05 μM, respectively, meaning that sporogen-AO1 can act as a relatively mild inhibitor against eukaryotic translation elongation.
{"title":"Sporogen-AO1 inhibits eukaryotic translation elongation","authors":"Kodai Machida, Shotaro Noseda, Seraya Miki, Mayumi Yuasa-Sunagawa, Hiroaki Imataka","doi":"10.1038/s41429-025-00817-8","DOIUrl":"10.1038/s41429-025-00817-8","url":null,"abstract":"Sporogen-AO1, a sporulation-promoting substance of Aspergillus oryzae was found to be a nonspecific translation inhibitor during screening of 22400 compounds. Sporogen-AO1 inhibited protein synthesis in cell-free protein synthesis (CFPS) systems derived from HeLa cell, wheat germ and yeast extracts, but not from E. coli S30 extracts. Sporogen-AO1 inhibited translation initiated from the cricket paralysis virus internal ribosome entry site, which does not require any translation initiation factor. Inhibition of translation due to sporogen-AO1was also observed in a CFPS system reconstituted with human translation factors and ribosomes; sporogen-AO1 decreased translation in the reconstituted CFPS system lacking aminoacyl-tRNA synthetases or translation termination factors. Thus, sporogen-AO1 targets the translation elongation phase comprising the ribosome and translation elongation factors. The IC50 values of sporogen-AO1 and cycloheximide were 7.44 ± 1.63 μM and 0.17 ± 0.05 μM, respectively, meaning that sporogen-AO1 can act as a relatively mild inhibitor against eukaryotic translation elongation.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"78 5","pages":"288-294"},"PeriodicalIF":2.7,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143722672","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}
Pub Date : 2025-03-24DOI: 10.1038/s41429-025-00818-7
Chengfeng Hou, Yuqing Wang, Xiangling Meng, Ling Lu, Peng Fu, Weiming Zhu, Yi Wang
Two new hydrogenated azaphilones (1 and 2), together with the known azaphilone (3) were isolated from the red soil-derived acid-tolerant fungus Penicillium purpureum OUCMDZ-019 by OSMAC (one strain many compounds) strategy. Their structures were determined by nuclear magnetic resonance (NMR) spectroscopy analysis and electronic circular dichroism (ECD) calculations. Compound 1 was the first reported azaphilone that salified with pyridine and chlorination occurred at C-1, and it exhibited potential inhibitory activity on melanin production as tyrosinase inhibitor in vivo. Furthermore, (+)-mitorubrinol acetate (3) showed significantly inhibitory activity against H1N1 with IC50 values of 58.6 μM (ribavirin, IC50 85.0 μM) as the first report.
{"title":"Bioactive hydrogenated azaphilones from acid-tolerant fungus Penicillium purpureum OUCMDZ-019","authors":"Chengfeng Hou, Yuqing Wang, Xiangling Meng, Ling Lu, Peng Fu, Weiming Zhu, Yi Wang","doi":"10.1038/s41429-025-00818-7","DOIUrl":"10.1038/s41429-025-00818-7","url":null,"abstract":"Two new hydrogenated azaphilones (1 and 2), together with the known azaphilone (3) were isolated from the red soil-derived acid-tolerant fungus Penicillium purpureum OUCMDZ-019 by OSMAC (one strain many compounds) strategy. Their structures were determined by nuclear magnetic resonance (NMR) spectroscopy analysis and electronic circular dichroism (ECD) calculations. Compound 1 was the first reported azaphilone that salified with pyridine and chlorination occurred at C-1, and it exhibited potential inhibitory activity on melanin production as tyrosinase inhibitor in vivo. Furthermore, (+)-mitorubrinol acetate (3) showed significantly inhibitory activity against H1N1 with IC50 values of 58.6 μM (ribavirin, IC50 85.0 μM) as the first report.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"78 5","pages":"281-287"},"PeriodicalIF":2.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702361","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}
Pub Date : 2025-03-19DOI: 10.1038/s41429-025-00815-w
Masaya Imoto, Yinzhi Lin, Siro Simizu
{"title":"Remembering Professor Kazuo Umezawa (6 December 1946– 12 January 2024)","authors":"Masaya Imoto, Yinzhi Lin, Siro Simizu","doi":"10.1038/s41429-025-00815-w","DOIUrl":"10.1038/s41429-025-00815-w","url":null,"abstract":"","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"78 5","pages":"336-338"},"PeriodicalIF":2.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41429-025-00815-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145123079","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":"Correction: New potentiators of amphotericin B activity, shodoamides A to C produced by Pseudophialophora sp. BF-0158","authors":"Akiho Yagi, Masahiro Kashima, Hiroyuki Ishijima, Hiroshi Tomoda, Ryuji Uchida","doi":"10.1038/s41429-025-00814-x","DOIUrl":"10.1038/s41429-025-00814-x","url":null,"abstract":"","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"78 5","pages":"339-340"},"PeriodicalIF":2.7,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41429-025-00814-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617793","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}
Pub Date : 2025-03-07DOI: 10.1038/s41429-025-00813-y
Shanshan Chang, Xinyue Huang, Meng Liu, Ning He, Yan Li, Hu Li, Yihong Li, Mengna Luo, Mengyuan Wang, Xichi Hu, Yunying Xie
Targeting drug-resistant Acinetobacter baumannii, two fungal strains, Epicoccum sp. 1-042 and Penicillium sp. 19-115, were identified from 35 fungi isolated from Tibet. Bioassay-guided isolation from Epicoccum sp. 1-042 yielded a novel cyclohexenone, epiconone (1), and parasitenone (2), while patulin (3) was isolated from Penicillium sp. 19-115. Structural elucidation was accomplished through comprehensive spectroscopic analysis and quantum chemistry calculations. The biosynthetic pathways of compounds 1 and 2 were proposed based on bioinformatics analysis. Compounds 1 − 3 exhibited antibacterial activity against carbapenem-resistant Acinetobacter baumannii (CRAB) with MIC values ranging from 4 to 128 μg mL-1.
{"title":"Epiconone, one novel cyclohexenone from endophytic fungi Epicoccum sp. 1-042","authors":"Shanshan Chang, Xinyue Huang, Meng Liu, Ning He, Yan Li, Hu Li, Yihong Li, Mengna Luo, Mengyuan Wang, Xichi Hu, Yunying Xie","doi":"10.1038/s41429-025-00813-y","DOIUrl":"10.1038/s41429-025-00813-y","url":null,"abstract":"Targeting drug-resistant Acinetobacter baumannii, two fungal strains, Epicoccum sp. 1-042 and Penicillium sp. 19-115, were identified from 35 fungi isolated from Tibet. Bioassay-guided isolation from Epicoccum sp. 1-042 yielded a novel cyclohexenone, epiconone (1), and parasitenone (2), while patulin (3) was isolated from Penicillium sp. 19-115. Structural elucidation was accomplished through comprehensive spectroscopic analysis and quantum chemistry calculations. The biosynthetic pathways of compounds 1 and 2 were proposed based on bioinformatics analysis. Compounds 1 − 3 exhibited antibacterial activity against carbapenem-resistant Acinetobacter baumannii (CRAB) with MIC values ranging from 4 to 128 μg mL-1.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"78 5","pages":"330-335"},"PeriodicalIF":2.7,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588110","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}
Three new compounds including two thiodiketopiperazine derivatives shovelmycins A–B (1–2), and one ansamycin derivative divergolide X (3) were isolated and identified from the culture extract of Streptomyces olivaceus HDN22-001, a marine actinomycete obtained from the deep-sea cold seep sediment sample collected from the South China Sea. Their structures and absolute configurations were determined by spectroscopic analyses and ECD calculations. Compound 1 exhibited the strongest DPPH radical scavenging activity with an IC50 value of 10.83 μM, which was better than that of the positive control vitamin C. And compound 2 was modestly cytotoxic against NCl-H446 cell with the IC50 value of 26.6 μM.
从南海深海冷渗漏沉积物中提取的海洋放线菌链霉菌（Streptomyces olivaceus HDN22-001）的培养物中分离鉴定出3个新化合物，包括2个硫代二酮哌嗪衍生物shovelmycins a - b（1-2）和1个安霉素衍生物divergolide X(3)。通过光谱分析和ECD计算确定了它们的结构和绝对构型。化合物1对DPPH自由基的清除能力最强，IC50值为10.83 μM，优于阳性对照维生素c；化合物2对NCl-H446细胞具有中等细胞毒性，IC50值为26.6 μM。
{"title":"The thiodiketopiperazine derivatives shovelmycin A–B and ansamycin derivative divergolide X from the cold-seep-derived Streptomyces olivaceus HDN22-001","authors":"Chen Li, Jiangli Cheng, Ruojin Liu, Xiaofei Huang, Luning Zhou, Guojian Zhang, Tianjiao Zhu, Dehai Li, Qian Che","doi":"10.1038/s41429-025-00812-z","DOIUrl":"10.1038/s41429-025-00812-z","url":null,"abstract":"Three new compounds including two thiodiketopiperazine derivatives shovelmycins A–B (1–2), and one ansamycin derivative divergolide X (3) were isolated and identified from the culture extract of Streptomyces olivaceus HDN22-001, a marine actinomycete obtained from the deep-sea cold seep sediment sample collected from the South China Sea. Their structures and absolute configurations were determined by spectroscopic analyses and ECD calculations. Compound 1 exhibited the strongest DPPH radical scavenging activity with an IC50 value of 10.83 μM, which was better than that of the positive control vitamin C. And compound 2 was modestly cytotoxic against NCl-H446 cell with the IC50 value of 26.6 μM.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"78 5","pages":"275-280"},"PeriodicalIF":2.7,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143558801","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}
Pub Date : 2025-02-21DOI: 10.1038/s41429-025-00811-0
Nadezhda P. Shlyk, Ekaterina A. Yurchenko, Elena V. Leshchenko, Ekaterina A. Chingizova, Artur R. Chingizov, Viktoria E. Chausova, Natalya N. Kirichuk, Yuliya V. Khudyakova, Mikhail V. Pivkin, Alexandr S. Antonov, Roman S. Popov, Marina P. Isaeva, Anton N. Yurchenko
Marine alga-derived fungal strain КММ 4176 was identified as Aspergillus niveoglaucus based on ITS region BenA, CaM and RPB2 gene sequence analysis. The anthraquinone derivatives emodin anthrone (1) and 4-hydroxyemodin anthrone (2), chromone derivative aloesone (3), and indole diketopiperazine alkaloid neoechinulin B (4) were isolated from the ethyl acetate extract of this fungus. In addition, UPLC MS data analysis of the KMM 4176 extract showed the presence of 17 echinulin-family alkaloids, as well as their biogenetic precursor cyclo(l-alanyl-l-tryptophyl) and a number of polyketide compounds. Emodin anthrone and 4-hydroxyemodin anthrone were found as inhibitors of biofilm formation by Staphylococcus aureus with half-maximal inhibitory concentrations (IC50) of 5.5 µM and 23.7 µM, respectively. Moreover, emodin anthrone (1) and 4-hydroxyemodin anthrone (2) inhibited staphylococcal sortase A activity with IC50 of 9.2 µM and 37.6 µM, respectively. Aloesone (3) also inhibited S. aureus biofilm formation but was less active. The first data on neoechinulin B (4) antibiofilm activity and sortase A inhibition were obtained. The positive effects of the isolated compounds on the growth of HaCaT keratinocytes infected with S. aureus were also observed.
{"title":"The secondary metabolites of the alga-derived fungus Aspergillus niveoglaucus КММ 4176 and their antimicrobial and antibiofilm activities","authors":"Nadezhda P. Shlyk, Ekaterina A. Yurchenko, Elena V. Leshchenko, Ekaterina A. Chingizova, Artur R. Chingizov, Viktoria E. Chausova, Natalya N. Kirichuk, Yuliya V. Khudyakova, Mikhail V. Pivkin, Alexandr S. Antonov, Roman S. Popov, Marina P. Isaeva, Anton N. Yurchenko","doi":"10.1038/s41429-025-00811-0","DOIUrl":"10.1038/s41429-025-00811-0","url":null,"abstract":"Marine alga-derived fungal strain КММ 4176 was identified as Aspergillus niveoglaucus based on ITS region BenA, CaM and RPB2 gene sequence analysis. The anthraquinone derivatives emodin anthrone (1) and 4-hydroxyemodin anthrone (2), chromone derivative aloesone (3), and indole diketopiperazine alkaloid neoechinulin B (4) were isolated from the ethyl acetate extract of this fungus. In addition, UPLC MS data analysis of the KMM 4176 extract showed the presence of 17 echinulin-family alkaloids, as well as their biogenetic precursor cyclo(l-alanyl-l-tryptophyl) and a number of polyketide compounds. Emodin anthrone and 4-hydroxyemodin anthrone were found as inhibitors of biofilm formation by Staphylococcus aureus with half-maximal inhibitory concentrations (IC50) of 5.5 µM and 23.7 µM, respectively. Moreover, emodin anthrone (1) and 4-hydroxyemodin anthrone (2) inhibited staphylococcal sortase A activity with IC50 of 9.2 µM and 37.6 µM, respectively. Aloesone (3) also inhibited S. aureus biofilm formation but was less active. The first data on neoechinulin B (4) antibiofilm activity and sortase A inhibition were obtained. The positive effects of the isolated compounds on the growth of HaCaT keratinocytes infected with S. aureus were also observed.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"78 5","pages":"314-329"},"PeriodicalIF":2.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473314","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}
Pub Date : 2025-02-18DOI: 10.1038/s41429-025-00809-8
Ramses Gallegos-Monterrosa, Jimena I. Cid-Uribe, Gustavo Delgado-Prudencio, Deyanira Pérez-Morales, María M. Banda, Alexis Téllez-Galván, Edson N. Carcamo-Noriega, Ulises Garza-Ramos, Richard N. Zare, Lourival D. Possani, Víctor H. Bustamante
Antibiotic-resistant bacteria pose a significant global health threat, particularly pathogens resistant to last-resort antibiotics, such as those listed as priority pathogens by the World Health Organization. Addressing this challenge requires the development of novel antimicrobial agents. Previously, we identified a blue 1,4-benzoquinone isolated from the venom of the Mexican scorpion Diplocentrus melici as a potent antimicrobial compound effective against Staphylococcus aureus and Mycobacterium tuberculosis. Moreover, we devised a cost-effective synthetic route for its production. In this study, we demonstrate that the blue benzoquinone exhibits antibacterial activity against additional pathogens, including the priority pathogen Acinetobacter baumannii. Notably, the compound effectively killed clinical strains of A. baumannii resistant to multiple antibiotics, including carbapenem and colistin. Furthermore, A. baumannii did not develop resistance to the benzoquinone even after multiple growth cycles under sub-inhibitory concentrations, unlike the tested antibiotics. These findings underscore the potential of this blue benzoquinone as a lead compound for the development of a new class of antibiotics targeting multidrug-resistant bacteria.
{"title":"Blue benzoquinone from scorpion venom shows bactericidal activity against drug-resistant strains of the priority pathogen Acinetobacter baumannii","authors":"Ramses Gallegos-Monterrosa, Jimena I. Cid-Uribe, Gustavo Delgado-Prudencio, Deyanira Pérez-Morales, María M. Banda, Alexis Téllez-Galván, Edson N. Carcamo-Noriega, Ulises Garza-Ramos, Richard N. Zare, Lourival D. Possani, Víctor H. Bustamante","doi":"10.1038/s41429-025-00809-8","DOIUrl":"10.1038/s41429-025-00809-8","url":null,"abstract":"Antibiotic-resistant bacteria pose a significant global health threat, particularly pathogens resistant to last-resort antibiotics, such as those listed as priority pathogens by the World Health Organization. Addressing this challenge requires the development of novel antimicrobial agents. Previously, we identified a blue 1,4-benzoquinone isolated from the venom of the Mexican scorpion Diplocentrus melici as a potent antimicrobial compound effective against Staphylococcus aureus and Mycobacterium tuberculosis. Moreover, we devised a cost-effective synthetic route for its production. In this study, we demonstrate that the blue benzoquinone exhibits antibacterial activity against additional pathogens, including the priority pathogen Acinetobacter baumannii. Notably, the compound effectively killed clinical strains of A. baumannii resistant to multiple antibiotics, including carbapenem and colistin. Furthermore, A. baumannii did not develop resistance to the benzoquinone even after multiple growth cycles under sub-inhibitory concentrations, unlike the tested antibiotics. These findings underscore the potential of this blue benzoquinone as a lead compound for the development of a new class of antibiotics targeting multidrug-resistant bacteria.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"78 4","pages":"235-245"},"PeriodicalIF":2.1,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41429-025-00809-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451049","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}
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