The antimicrobial activity of tumescenamide C against the scab-forming S. scabiei NBRC13768 was confirmed with a potent IC50 value (1.5 μg/mL). Three tumescenamide C-resistant S. scabiei strains were generated to compare their gene variants. All three resistant strains contained nonsynonymous variants in genes related to cellobiose/cellotriose transport system components; cebF1, cebF2, and cebG2, which are responsible for the production of the phytotoxin thaxtomin A. Decrease in thaxtomin A production and the virulence of the three resistant strains were revealed by the LC/MS analysis and necrosis assay, respectively. Although the nonsynonymous variants were insufficient for identifying the molecular target of tumescenamide C, the cell wall component wall teichoic acid (WTA) was observed to bind significantly to tumescenamide C. Moreover, changes in the WTA contents were detected in the tumescenamide C-resistant strains. These results imply that tumescenamide C targets the cell wall system to exert antimicrobial effects on S. scabiei.
图森酰胺 C 对疥疮形成菌 NBRC13768 的抗菌活性得到了证实，其 IC50 值（1.5 μg/mL）非常有效。为了比较疥癣病菌的基因变异，生成了三株对 Tumescenamide C 具有抗性的疥癣病菌。这三种抗性菌株都含有与纤维生物糖/细胞三糖转运系统成分有关的非同义变体基因：cebF1、cebF2和cebG2，它们负责产生植物毒素thaxomin A。虽然非同义变体不足以确定噻菌胺 C 的分子靶标，但观察到细胞壁成分壁茶酸 (WTA) 与噻菌胺 C 有显著结合。这些结果表明，妥布酰胺 C 以细胞壁系统为目标，对疥螨产生抗菌作用。
{"title":"Tumescenamide C, a cyclic lipodepsipeptide from Streptomyces sp. KUSC_F05, exerts antimicrobial activity against the scab-forming actinomycete Streptomyces scabiei","authors":"Kensuke Kaneko, Marika Mieda, Yulu Jiang, Nobuaki Takahashi, Hideaki Kakeya","doi":"10.1038/s41429-024-00716-4","DOIUrl":"10.1038/s41429-024-00716-4","url":null,"abstract":"The antimicrobial activity of tumescenamide C against the scab-forming S. scabiei NBRC13768 was confirmed with a potent IC50 value (1.5 μg/mL). Three tumescenamide C-resistant S. scabiei strains were generated to compare their gene variants. All three resistant strains contained nonsynonymous variants in genes related to cellobiose/cellotriose transport system components; cebF1, cebF2, and cebG2, which are responsible for the production of the phytotoxin thaxtomin A. Decrease in thaxtomin A production and the virulence of the three resistant strains were revealed by the LC/MS analysis and necrosis assay, respectively. Although the nonsynonymous variants were insufficient for identifying the molecular target of tumescenamide C, the cell wall component wall teichoic acid (WTA) was observed to bind significantly to tumescenamide C. Moreover, changes in the WTA contents were detected in the tumescenamide C-resistant strains. These results imply that tumescenamide C targets the cell wall system to exert antimicrobial effects on S. scabiei.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 6","pages":"353-364"},"PeriodicalIF":3.3,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140208200","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}
Okichromanone (1), a new chromanone, was isolated from the culture extract of a sponge-derived actinomycete Microbispora, along with known 1-hydroxyphenazine (2). Compound 1 was elucidated to exist as a mixture of two isomeric structures (1a and 1b) at a ratio of nearly 3:2. Compounds 1 and 2 showed anti HSV-I activity with IC50 values 40 and 86 μM, respectively, and anti HSV-II activity with IC50 values 59 and 123 μM, respectively.
{"title":"Okichromanone, a new antiviral chromanone from a marine-derived Microbispora","authors":"Marwa Elsbaey, Takahiro Jomori, Junichi Tanaka, Naoya Oku, Yasuhiro Igarashi","doi":"10.1038/s41429-024-00718-2","DOIUrl":"10.1038/s41429-024-00718-2","url":null,"abstract":"Okichromanone (1), a new chromanone, was isolated from the culture extract of a sponge-derived actinomycete Microbispora, along with known 1-hydroxyphenazine (2). Compound 1 was elucidated to exist as a mixture of two isomeric structures (1a and 1b) at a ratio of nearly 3:2. Compounds 1 and 2 showed anti HSV-I activity with IC50 values 40 and 86 μM, respectively, and anti HSV-II activity with IC50 values 59 and 123 μM, respectively.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 6","pages":"389-392"},"PeriodicalIF":3.3,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140195104","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 : 2024-03-22DOI: 10.1038/s41429-024-00720-8
Dae-Won Ki, Dae-Cheol Choi, Yeong-Seon Won, Seung-Jae Lee, Young-Hee Kim, In-Kyoung Lee, Bong-Sik Yun
Three new phthalide derivatives (1‒3) together with two known compounds, erinaceolactone B (4) and hericerin III (5), were isolated from the culture broth of Dentipellis fragilis. The chemical structures of 1‒5 were determined by analyses of their 1D-, 2D-NMR, and MS. The absolute configuration of 1 was determined by CD analysis. The isolated compounds were assessed for their cytotoxic activities against A549, DU145, HCT116, and HT1080 cancer cell lines. Compounds 1‒5 showed strong cytotoxic activities against DU145, with IC50 values ranging from 14.3 to 16.1 µM. Additionally, all compounds showed moderate or weak cytotoxic activities against all cell lines except for compounds 4 and 1 which showed no cytotoxic activities against A549 and HCT116 cancer cell lines, respectively. Against HT1080 cancer cell line, only compound 2 displayed moderate cytotoxic activity.
{"title":"Three new phthalide derivatives from culture broth of Dentipellis fragilis and their cytotoxic activities","authors":"Dae-Won Ki, Dae-Cheol Choi, Yeong-Seon Won, Seung-Jae Lee, Young-Hee Kim, In-Kyoung Lee, Bong-Sik Yun","doi":"10.1038/s41429-024-00720-8","DOIUrl":"10.1038/s41429-024-00720-8","url":null,"abstract":"Three new phthalide derivatives (1‒3) together with two known compounds, erinaceolactone B (4) and hericerin III (5), were isolated from the culture broth of Dentipellis fragilis. The chemical structures of 1‒5 were determined by analyses of their 1D-, 2D-NMR, and MS. The absolute configuration of 1 was determined by CD analysis. The isolated compounds were assessed for their cytotoxic activities against A549, DU145, HCT116, and HT1080 cancer cell lines. Compounds 1‒5 showed strong cytotoxic activities against DU145, with IC50 values ranging from 14.3 to 16.1 µM. Additionally, all compounds showed moderate or weak cytotoxic activities against all cell lines except for compounds 4 and 1 which showed no cytotoxic activities against A549 and HCT116 cancer cell lines, respectively. Against HT1080 cancer cell line, only compound 2 displayed moderate cytotoxic activity.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 6","pages":"338-344"},"PeriodicalIF":3.3,"publicationDate":"2024-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140195105","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 : 2024-03-21DOI: 10.1038/s41429-024-00717-3
Rakshit Manhas, Arti Rathore, Ujwal Havelikar, Shavi Mahajan, Sumit G. Gandhi, Avisek Mahapa
Antimicrobial resistance has emerged as a covert global health crisis, posing a significant threat to humanity. If left unaddressed, it is poised to become the foremost cause of mortality worldwide. Among the multitude of resistant bacterial pathogens, Pseudomonas aeruginosa, a Gram-negative, facultative bacterium, has been responsible for mild to deadly infections. It is now enlisted as a global critical priority pathogen by WHO. Urgent measures are required to combat this formidable pathogen, necessitating the development of novel anti-pseudomonal drugs. To confront this pressing issue, we conducted an extensive screening of 3561 compounds from the ChemDiv library, resulting in the discovery of potent anti-pseudomonal quinazoline derivatives. Among the identified compounds, IDD-8E has emerged as a lead molecule, exhibiting exceptional efficacy against P. aeruginosa while displaying no cytotoxicity. Moreover, IDD-8E demonstrated significant pseudomonal killing, disruption of pseudomonal biofilm and other anti-bacterial properties comparable to a well-known antibiotic rifampicin. Additionally, IDD-8E’s synergy with different antibiotics further strengthens its potential as a powerful anti-pseudomonal agent. IDD-8E also exhibited significant antimicrobial efficacy against other ESKAPE pathogens. Moreover, we elucidated the Structure-Activity-Relationship (SAR) of IDD-8E targeting the essential WaaP protein in P. aeruginosa. Altogether, our findings emphasize the promise of IDD-8E as a clinical candidate for novel anti-pseudomonal drugs, offering hope in the battle against antibiotic resistance and its devastating impact on global health.
{"title":"Uncovering the potentiality of quinazoline derivatives against Pseudomonas aeruginosa with antimicrobial synergy and SAR analysis","authors":"Rakshit Manhas, Arti Rathore, Ujwal Havelikar, Shavi Mahajan, Sumit G. Gandhi, Avisek Mahapa","doi":"10.1038/s41429-024-00717-3","DOIUrl":"10.1038/s41429-024-00717-3","url":null,"abstract":"Antimicrobial resistance has emerged as a covert global health crisis, posing a significant threat to humanity. If left unaddressed, it is poised to become the foremost cause of mortality worldwide. Among the multitude of resistant bacterial pathogens, Pseudomonas aeruginosa, a Gram-negative, facultative bacterium, has been responsible for mild to deadly infections. It is now enlisted as a global critical priority pathogen by WHO. Urgent measures are required to combat this formidable pathogen, necessitating the development of novel anti-pseudomonal drugs. To confront this pressing issue, we conducted an extensive screening of 3561 compounds from the ChemDiv library, resulting in the discovery of potent anti-pseudomonal quinazoline derivatives. Among the identified compounds, IDD-8E has emerged as a lead molecule, exhibiting exceptional efficacy against P. aeruginosa while displaying no cytotoxicity. Moreover, IDD-8E demonstrated significant pseudomonal killing, disruption of pseudomonal biofilm and other anti-bacterial properties comparable to a well-known antibiotic rifampicin. Additionally, IDD-8E’s synergy with different antibiotics further strengthens its potential as a powerful anti-pseudomonal agent. IDD-8E also exhibited significant antimicrobial efficacy against other ESKAPE pathogens. Moreover, we elucidated the Structure-Activity-Relationship (SAR) of IDD-8E targeting the essential WaaP protein in P. aeruginosa. Altogether, our findings emphasize the promise of IDD-8E as a clinical candidate for novel anti-pseudomonal drugs, offering hope in the battle against antibiotic resistance and its devastating impact on global health.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 6","pages":"365-381"},"PeriodicalIF":3.3,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140186338","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 : 2024-03-19DOI: 10.1038/s41429-024-00714-6
Annalisa Mortoni, Eugenio Castelli, Teresa Recca, Paolo Quadrelli
A complete and detailed characterization of Rapamycin (1) and Prolylrapamycin (2) has been conducted by homo- and hetero-nuclear NMR experiments in DMSO-d6 along with HRMS and FT-IR spectra and DSCs analyses. The NMR experiments allowed the assignment of every single proton and carbon atom belonging to the two structures and the definitive confirm of the presence of a pyrrolidine ring in Prolylrapamycin (2) in place of the piperidine ring that characterizes the structure of Sirolimus.
{"title":"Structure of prolylrapamycin: confirmation through a revised and detailed NMR assignment study","authors":"Annalisa Mortoni, Eugenio Castelli, Teresa Recca, Paolo Quadrelli","doi":"10.1038/s41429-024-00714-6","DOIUrl":"10.1038/s41429-024-00714-6","url":null,"abstract":"A complete and detailed characterization of Rapamycin (1) and Prolylrapamycin (2) has been conducted by homo- and hetero-nuclear NMR experiments in DMSO-d6 along with HRMS and FT-IR spectra and DSCs analyses. The NMR experiments allowed the assignment of every single proton and carbon atom belonging to the two structures and the definitive confirm of the presence of a pyrrolidine ring in Prolylrapamycin (2) in place of the piperidine ring that characterizes the structure of Sirolimus.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 6","pages":"345-352"},"PeriodicalIF":3.3,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41429-024-00714-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140169206","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}
The first report of transmissible carbapenem resistance encoded by blaIMP-1 was discovered in Pseudomonas aeruginosa GN17203 in 1988, and blaIMP-1 has since been detected in other bacteria, including Enterobacterales. Currently, many variants of blaIMPs exist, and point mutations in the blaIMP promoter have been shown to alter promoter strength. For example, the promoter (Pc) of blaIMP-1, first reported in P. aeruginosa GN17203, was a weak promoter (PcW) with low-level expression intensity. This study investigates whether point mutations in the promoter region have helped to create strong promoters under antimicrobial selection pressure. Using bioinformatic approaches, we retrieved 115 blaIMPs from 14,529 genome data of Pseudomonadota and performed multiple alignment analyses. The results of promoter analysis of the 115 retrieved blaIMPs showed that most of them used the Pc located in class 1 integrons (n = 112, 97.4%). The promoter analysis by year revealed that the blaIMP population with the strong promoter, PcS, was transient. In contrast, the PcW-TG population, which had acquired a TGn-extended −10 motif in PcW and had an intermediate promoter strength, gradually spread throughout the world. An inverse correlation between Pc promoter strength and Intl1 integrase excision efficiency has been reported previously [1]. Because of this trade-off, it is unlikely that blaIMPs with strong promoters will increase rapidly, but the possibility that promoter strength will increase with the use of other integrons cannot be ruled out. Monitoring of the blaIMP genes, including promoter analysis, is necessary for global surveillance of carbapenem-resistant bacteria.
{"title":"Correlation between the spread of IMP-producing bacteria and the promoter strength of blaIMP genes","authors":"Yuta Kikuchi, Mariko Yoshida, Asaomi Kuwae, Yukihiro Asami, Yuki Inahashi, Akio Abe","doi":"10.1038/s41429-024-00715-5","DOIUrl":"10.1038/s41429-024-00715-5","url":null,"abstract":"The first report of transmissible carbapenem resistance encoded by blaIMP-1 was discovered in Pseudomonas aeruginosa GN17203 in 1988, and blaIMP-1 has since been detected in other bacteria, including Enterobacterales. Currently, many variants of blaIMPs exist, and point mutations in the blaIMP promoter have been shown to alter promoter strength. For example, the promoter (Pc) of blaIMP-1, first reported in P. aeruginosa GN17203, was a weak promoter (PcW) with low-level expression intensity. This study investigates whether point mutations in the promoter region have helped to create strong promoters under antimicrobial selection pressure. Using bioinformatic approaches, we retrieved 115 blaIMPs from 14,529 genome data of Pseudomonadota and performed multiple alignment analyses. The results of promoter analysis of the 115 retrieved blaIMPs showed that most of them used the Pc located in class 1 integrons (n = 112, 97.4%). The promoter analysis by year revealed that the blaIMP population with the strong promoter, PcS, was transient. In contrast, the PcW-TG population, which had acquired a TGn-extended −10 motif in PcW and had an intermediate promoter strength, gradually spread throughout the world. An inverse correlation between Pc promoter strength and Intl1 integrase excision efficiency has been reported previously [1]. Because of this trade-off, it is unlikely that blaIMPs with strong promoters will increase rapidly, but the possibility that promoter strength will increase with the use of other integrons cannot be ruled out. Monitoring of the blaIMP genes, including promoter analysis, is necessary for global surveillance of carbapenem-resistant bacteria.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 5","pages":"315-323"},"PeriodicalIF":3.3,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41429-024-00715-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140141165","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 : 2024-03-15DOI: 10.1038/s41429-024-00719-1
Mark V. Savitskii, Natalia E. Moskaleva, Alex Brito, Pavel A. Markin, Nailya A. Zigangirova, Anna V. Soloveva, Anna B. Sheremet, Natalia E. Bondareva, Nadezhda L. Lubenec, Franco Tagliaro, Vadim V. Tarasov, Kristina A. Tatzhikova, Svetlana A. Appolonova
Growing antimicrobial resistance has accelerated the development of anti-virulence drugs to suppress bacterial toxicity without affecting cell viability. Fluorothiazinon (FT), an anti-virulence, type three secretion system and flagella motility inhibitor which has shown promise to suppress drug-resistant pathogens having the potential to enhance the efficacy of commonly prescribed antibiotics when used in combination. In this study we characterized the pharmacokinetics, tissue distribution, bioavailability and excretion of FT in rats and rabbits. FT presented a dose-proportional linear increase in the blood of rats. Tissue distribution profiling confirmed that FT distributes to all organs being substantially higher than in the blood of rats. The bioavailability of FT was higher when administered with starch than with water implying FT should be ideally dosed with food. FT was primarily excreted in the feces in rats and rabbits while negligible amounts are recovered from the urine.
抗菌药耐药性的不断增加加速了抗病毒药物的开发，以在不影响细胞活力的情况下抑制细菌毒性。氟噻嗪侬（FT）是一种抗病毒药、三型分泌系统和鞭毛运动抑制剂，有望抑制耐药性病原体，在联合使用时有可能提高常用抗生素的疗效。在这项研究中，我们研究了 FT 在大鼠和兔子体内的药代动力学、组织分布、生物利用度和排泄情况。FT 在大鼠血液中呈剂量比例线性增加。组织分布剖析证实，FT 在所有器官中的分布均远高于在大鼠血液中的分布。与淀粉一起给药时，FT 的生物利用率高于与水一起给药时，这意味着 FT 最好与食物一起给药。大鼠和家兔的 FT 主要通过粪便排泄，而从尿液中回收的量微乎其微。
{"title":"Pharmacokinetics, tissue distribution, bioavailability and excretion of the anti-virulence drug Fluorothiazinon in rats and rabbits","authors":"Mark V. Savitskii, Natalia E. Moskaleva, Alex Brito, Pavel A. Markin, Nailya A. Zigangirova, Anna V. Soloveva, Anna B. Sheremet, Natalia E. Bondareva, Nadezhda L. Lubenec, Franco Tagliaro, Vadim V. Tarasov, Kristina A. Tatzhikova, Svetlana A. Appolonova","doi":"10.1038/s41429-024-00719-1","DOIUrl":"10.1038/s41429-024-00719-1","url":null,"abstract":"Growing antimicrobial resistance has accelerated the development of anti-virulence drugs to suppress bacterial toxicity without affecting cell viability. Fluorothiazinon (FT), an anti-virulence, type three secretion system and flagella motility inhibitor which has shown promise to suppress drug-resistant pathogens having the potential to enhance the efficacy of commonly prescribed antibiotics when used in combination. In this study we characterized the pharmacokinetics, tissue distribution, bioavailability and excretion of FT in rats and rabbits. FT presented a dose-proportional linear increase in the blood of rats. Tissue distribution profiling confirmed that FT distributes to all organs being substantially higher than in the blood of rats. The bioavailability of FT was higher when administered with starch than with water implying FT should be ideally dosed with food. FT was primarily excreted in the feces in rats and rabbits while negligible amounts are recovered from the urine.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 6","pages":"382-388"},"PeriodicalIF":3.3,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140141166","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 : 2024-03-11DOI: 10.1038/s41429-024-00713-7
Aoi Kimishima, Masako Honsho, Junsei Terai, Paul Wasuwanich, Sota Honma, Hidehito Matsui, Hideaki Hanaki, Yukihiro Asami
The emergence and spread of antimicrobial resistance are global threats. Pseudomonas aeruginosa (P. aeruginosa) is responsible for a substantial proportion of this global health issue because of its intrinsic resistance to many antibiotics due to the impermeability of its outer membrane and its multidrug efflux pump systems. Therefore, therapeutic drugs are limited, and the development of new drugs is extremely challenging. As an alternative approach, we focused on a combinational treatment strategy and found that 5-O-mycaminosyltylonolide (OMT) showed potent antibacterial activity against P. aeruginosa in the presence of an efflux pump inhibitor, phenylalanine-arginine beta-naphthylamide (PAβN). In this report, we prepared a PAβN derivative and compared the potentiation activity of OMT by PAβNs against multidrug-resistant P. aeruginosa clinical isolates.
{"title":"Efflux pump inhibitor, phenylalanine-arginine beta-naphthylamide analog potentiates the activity of 5-O-mycaminosyltylonolide for multi-drug resistant Pseudomonas aeruginosa","authors":"Aoi Kimishima, Masako Honsho, Junsei Terai, Paul Wasuwanich, Sota Honma, Hidehito Matsui, Hideaki Hanaki, Yukihiro Asami","doi":"10.1038/s41429-024-00713-7","DOIUrl":"10.1038/s41429-024-00713-7","url":null,"abstract":"The emergence and spread of antimicrobial resistance are global threats. Pseudomonas aeruginosa (P. aeruginosa) is responsible for a substantial proportion of this global health issue because of its intrinsic resistance to many antibiotics due to the impermeability of its outer membrane and its multidrug efflux pump systems. Therefore, therapeutic drugs are limited, and the development of new drugs is extremely challenging. As an alternative approach, we focused on a combinational treatment strategy and found that 5-O-mycaminosyltylonolide (OMT) showed potent antibacterial activity against P. aeruginosa in the presence of an efflux pump inhibitor, phenylalanine-arginine beta-naphthylamide (PAβN). In this report, we prepared a PAβN derivative and compared the potentiation activity of OMT by PAβNs against multidrug-resistant P. aeruginosa clinical isolates.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 5","pages":"331-333"},"PeriodicalIF":3.3,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140102888","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 : 2024-03-04DOI: 10.1038/s41429-024-00707-5
So-ichiro Kimura, Yoshihiro Watanabe, Shiori Shibasaki, Naoya Shinzato, Yuki Inahashi, Toshiaki Sunazuka, Rei Hokari, Aki Ishiyama, Masato Iwatsuki
Two new antimalarial compounds, named prenylpyridones A (1) and B (2), were discovered from the actinomycete cultured material of Streptomyces sp. RBL-0292 isolated from the soil on Hamahiga Island in Okinawa prefecture. The structures of 1 and 2 were elucidated as new iromycin analogs having α-pyridone ring by MS and NMR analyses. Compounds 1 and 2 showed moderate in vitro antimalarial activity against chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum strains, with IC50 values ranging from 80.7 to 106.7 µM.
{"title":"New antimalarial iromycin analogs produced by Streptomyces sp. RBL-0292","authors":"So-ichiro Kimura, Yoshihiro Watanabe, Shiori Shibasaki, Naoya Shinzato, Yuki Inahashi, Toshiaki Sunazuka, Rei Hokari, Aki Ishiyama, Masato Iwatsuki","doi":"10.1038/s41429-024-00707-5","DOIUrl":"10.1038/s41429-024-00707-5","url":null,"abstract":"Two new antimalarial compounds, named prenylpyridones A (1) and B (2), were discovered from the actinomycete cultured material of Streptomyces sp. RBL-0292 isolated from the soil on Hamahiga Island in Okinawa prefecture. The structures of 1 and 2 were elucidated as new iromycin analogs having α-pyridone ring by MS and NMR analyses. Compounds 1 and 2 showed moderate in vitro antimalarial activity against chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum strains, with IC50 values ranging from 80.7 to 106.7 µM.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 5","pages":"272-277"},"PeriodicalIF":3.3,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140029553","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 : 2024-03-04DOI: 10.1038/s41429-024-00704-8
Noha Anwar Hassuna, Eman M. Rabea, W. K. M. Mahdi, Wedad M. Abdelraheem
The multidrug-resistant clone identified as Escherichia coli sequence type 131 (E. coli ST131) has spread world-wide. This study sought to ascertain the frequency and biofilm formation of E. coli ST131 isolated from children with various malignancies. A total of 60 uropathogenic E. coli (UPEC) isolates from children without cancer and 30 UPEC isolates from children with cancer were assessed in this study. The microdilution method was used to investigate the sensitivity of bacteria to antibiotics. The microtiter plate (MTP) approach was used to phenotypically assess biofilm formation. The lasR, pelA, and lecA biofilm-encoding genes were detected by PCR in biofilm-producing isolates of E. coli. Thirty-seven out of 90 E. coli isolates were found to be ST131 (41.1%), with 17 (56.7%) from cancer-affected children and 20 (33.3%) from children without cancer, respectively (P-value = 0.036). The frequency of antimicrobial resistance was higher in ST131 strains were compared to non-ST131 strains and when they were isolated from healthy children vs. those who had cancer. In contrast to non-ST131 isolates, ST131 isolates were more biofilm-producers. There was a significant difference between the percentage of biofilm producers between the 22 (100%) ST131-O16 isolates and the 13 (86.7%) ST131-O25b isolates (P-value = 0.04). Children with cancer are more likely than children without cancer to develop biofilm forming E. coli ST131, the latter having a higher profile of antibiotic resistance. Interestingly, E. coli ST131 isolates from non-cancer patients had higher levels of overall antibiotic resistance and while more E. coli ST131isolates from cancer patients formed biofilms.
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