Sporangimicins A–D (1–4), four anomeric pairs of diacyl disaccharides that represent a new metabolite class, were discovered from the culture extract of an actinomycete Pseudosporangium sp. RD061809. Compounds 1–4 caused peak separation in the HPLC chromatogram and partial duplication of the NMR resonances by anomeric interconversion of a maltose core modified at the two sugar 6-positions with an isobutanoyl and a methyl-branched long-chain dienoyl groups. A highlight of the structure elucidation was application of Ohrui-Akasaka’s method to a chromatographically inseparable mixture of 3 and 4, which proved the composition ratio of 3 and 4 to be 82:18 and the R/S ratio at the anteiso-methyl bearing chiral center in 3 to be 66:34. Compounds 1–4 showed antimicrobial activity against Gram-positive bacteria and modest cytotoxicity toward P388 murine leukemia cells.
{"title":"Sporangimicins A–D, acylated maltose derivatives from a rare actinomycete of the genus Pseudosporangium","authors":"Yasuhiro Igarashi, Miku Nohda, Hiroki Katoh, Zhiwei Zhang, Desy Wulan Triningsih, Md. Rokon Ul Karim, Kazuaki Akasaka, Enjuro Harunari, Naoya Oku","doi":"10.1038/s41429-024-00768-6","DOIUrl":"10.1038/s41429-024-00768-6","url":null,"abstract":"Sporangimicins A–D (1–4), four anomeric pairs of diacyl disaccharides that represent a new metabolite class, were discovered from the culture extract of an actinomycete Pseudosporangium sp. RD061809. Compounds 1–4 caused peak separation in the HPLC chromatogram and partial duplication of the NMR resonances by anomeric interconversion of a maltose core modified at the two sugar 6-positions with an isobutanoyl and a methyl-branched long-chain dienoyl groups. A highlight of the structure elucidation was application of Ohrui-Akasaka’s method to a chromatographically inseparable mixture of 3 and 4, which proved the composition ratio of 3 and 4 to be 82:18 and the R/S ratio at the anteiso-methyl bearing chiral center in 3 to be 66:34. Compounds 1–4 showed antimicrobial activity against Gram-positive bacteria and modest cytotoxicity toward P388 murine leukemia cells.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 11","pages":"713-720"},"PeriodicalIF":2.1,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41429-024-00768-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142114913","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 : 2024-08-29DOI: 10.1038/s41429-024-00769-5
Merve Yildirim, Bunyamin Ozgeris, Arzu Gormez
This study focuses on the activity of previously reported imine and β-lactam derivatives against methicillin-resistant Staphylococcus aureus (MRSA) isolates. The presence of mecA and blaZ genes in the isolates was determined, and the minimum inhibitory concentration (MIC) values were determined based on the antibacterial activity against these isolates. Active compounds were selected and their ability to act against resistant isolates in vitro was determined. Concurrently, biochemical (nitrocefin) and molecular (qRT-PCR) tests were used to investigate the ability of the compounds to induce resistance genes in MRSA isolates. The cytotoxicity of the compounds on human dermal fibroblasts (HDF) was investigated. The MIC values of compounds (10) and (12) against MSSA and MRSA isolates were 7.81 and 15.62 μg ml−1, respectively. The most active compounds were identified as (10) and (12), and it was observed that the isolates did not develop resistance to these compounds in vitro. These compounds were found to inhibit β-lactamase, reduce the expression of resistance genes, and exhibit reduced HDF cell toxicity in a dose-dependent manner. According to the findings of the study, it can be concluded that these compounds show promise as hits with an interesting mechanism of action for further chemical modifications to develop new MRSA inhibitors.
{"title":"The effect of novel β-lactam derivatives synthesized from substituted phenethylamines on resistance genes of MRSA isolates","authors":"Merve Yildirim, Bunyamin Ozgeris, Arzu Gormez","doi":"10.1038/s41429-024-00769-5","DOIUrl":"10.1038/s41429-024-00769-5","url":null,"abstract":"This study focuses on the activity of previously reported imine and β-lactam derivatives against methicillin-resistant Staphylococcus aureus (MRSA) isolates. The presence of mecA and blaZ genes in the isolates was determined, and the minimum inhibitory concentration (MIC) values were determined based on the antibacterial activity against these isolates. Active compounds were selected and their ability to act against resistant isolates in vitro was determined. Concurrently, biochemical (nitrocefin) and molecular (qRT-PCR) tests were used to investigate the ability of the compounds to induce resistance genes in MRSA isolates. The cytotoxicity of the compounds on human dermal fibroblasts (HDF) was investigated. The MIC values of compounds (10) and (12) against MSSA and MRSA isolates were 7.81 and 15.62 μg ml−1, respectively. The most active compounds were identified as (10) and (12), and it was observed that the isolates did not develop resistance to these compounds in vitro. These compounds were found to inhibit β-lactamase, reduce the expression of resistance genes, and exhibit reduced HDF cell toxicity in a dose-dependent manner. According to the findings of the study, it can be concluded that these compounds show promise as hits with an interesting mechanism of action for further chemical modifications to develop new MRSA inhibitors.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 12","pages":"802-811"},"PeriodicalIF":2.1,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142114914","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}
A new actinomycete strain, ODS25T, exhibited antimicrobial activity against Bacillus subtilis, Kocuria rhizophila, Staphylococcus aureus, Staphylococcus epidermidis, Candida albicans, Candida tropicalis, was isolated from the ants, Odontomachus simillimus, collected from National Science Museum Thailand, Pathum Thani, Thailand. A polyphasic technique was used to characterize the taxonomic position. The morphological and chemotaxonomic properties of the strain are typical of members of the genus Streptomyces. Strain ODS25T contained ll-diaminopimelic and glucose in the whole-cell hydrolysate. The major cellular fatty acids were iso-C16:0, iso-C15:0, and anteiso-C15:0. The polar lipids were phosphatidylethanolamine, phosphatidylinositol mannosides, phosphatidylinositol, diphosphatidylglycerol, phosphatidylglycerol, three unidentified phospholipids, three unidentified amino lipids and two unidentified lipids. The menaquinones were MK-9(H6), MK-9(H8), and MK-9(H4). The G + C content of the genomic DNA was 71.3%. The 16 S rRNA gene sequence analysis demonstrated that the strain had the highest similarity to Streptomyces lusitanus NBRC 13464T (98.07%) but shared the phylogenetic neighbour with Streptomyces sulfonofaciens JCM 5069T. Both digital DNA–DNA hybridization and average nucleotide identity values among strain ODS25T and its associated Streptomyces type strains fell within the values lower than the threshold for differentiate the strain to the same species. Based on the phenotypic characteristics and genotypic distinctiveness, strain ODS25T is considered a novel species within the genus Streptomyces, for which the name Streptomyces odontomachi sp. nov. is proposed. The type strain is ODS25T (=TBRC 16204T=NBRC 115862T).
{"title":"Streptomyces odontomachi sp. nov., a novel actinobacterium with antimicrobial potential isolated from ants (Odontomachus simillimus Smith, 1858)","authors":"Tuangrat Tunvongvinis, Weeyawat Jaitrong, Chanwit Suriyachadkun, Paranee Sripreechasak, Somboon Tanasupawat, Wongsakorn Phongsopitanun","doi":"10.1038/s41429-024-00766-8","DOIUrl":"10.1038/s41429-024-00766-8","url":null,"abstract":"A new actinomycete strain, ODS25T, exhibited antimicrobial activity against Bacillus subtilis, Kocuria rhizophila, Staphylococcus aureus, Staphylococcus epidermidis, Candida albicans, Candida tropicalis, was isolated from the ants, Odontomachus simillimus, collected from National Science Museum Thailand, Pathum Thani, Thailand. A polyphasic technique was used to characterize the taxonomic position. The morphological and chemotaxonomic properties of the strain are typical of members of the genus Streptomyces. Strain ODS25T contained ll-diaminopimelic and glucose in the whole-cell hydrolysate. The major cellular fatty acids were iso-C16:0, iso-C15:0, and anteiso-C15:0. The polar lipids were phosphatidylethanolamine, phosphatidylinositol mannosides, phosphatidylinositol, diphosphatidylglycerol, phosphatidylglycerol, three unidentified phospholipids, three unidentified amino lipids and two unidentified lipids. The menaquinones were MK-9(H6), MK-9(H8), and MK-9(H4). The G + C content of the genomic DNA was 71.3%. The 16 S rRNA gene sequence analysis demonstrated that the strain had the highest similarity to Streptomyces lusitanus NBRC 13464T (98.07%) but shared the phylogenetic neighbour with Streptomyces sulfonofaciens JCM 5069T. Both digital DNA–DNA hybridization and average nucleotide identity values among strain ODS25T and its associated Streptomyces type strains fell within the values lower than the threshold for differentiate the strain to the same species. Based on the phenotypic characteristics and genotypic distinctiveness, strain ODS25T is considered a novel species within the genus Streptomyces, for which the name Streptomyces odontomachi sp. nov. is proposed. The type strain is ODS25T (=TBRC 16204T=NBRC 115862T).","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 11","pages":"727-736"},"PeriodicalIF":2.1,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41429-024-00766-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914625","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 : 2024-08-08DOI: 10.1038/s41429-024-00764-w
Antonius R. B. Ola
Most of the natural products containing tetramic acid have trans configuration of the decalin moiety. Undana A (1), a new cis decalin-bearing tetramic acid metabolite was isolated from endophytic fungi Nigrospora oryzae associated with Avicennia marina. The structure was determined based on the mass and NMR spectral data together with the comparison of the literature. This is the first report of cis decalin-tetramic acid metabolite from the mangrove endophytic fungus. Compound 1 was tested for cytotoxic against L5178Y mouse cancer cells and antibacterial activity against several gram-positive including MRSA and gram-negative bacteria but was found inactive.
{"title":"Cis -decalin tetramic acid metabolite from a mangrove derived endophytic fungus Nigrospora oryzae","authors":"Antonius R. B. Ola","doi":"10.1038/s41429-024-00764-w","DOIUrl":"10.1038/s41429-024-00764-w","url":null,"abstract":"Most of the natural products containing tetramic acid have trans configuration of the decalin moiety. Undana A (1), a new cis decalin-bearing tetramic acid metabolite was isolated from endophytic fungi Nigrospora oryzae associated with Avicennia marina. The structure was determined based on the mass and NMR spectral data together with the comparison of the literature. This is the first report of cis decalin-tetramic acid metabolite from the mangrove endophytic fungus. Compound 1 was tested for cytotoxic against L5178Y mouse cancer cells and antibacterial activity against several gram-positive including MRSA and gram-negative bacteria but was found inactive.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 11","pages":"778-782"},"PeriodicalIF":2.1,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141908401","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 : 2024-08-01DOI: 10.1038/s41429-024-00761-z
Ashraf A. Kadry, May A. El-Antrawy, Amira M. El-Ganiny
Escherichia coli and Klebsiella pneumoniae are important members of the Enterobacteriaceae family, involved in many infections. The increased resistance rate towards β-lactams and fluoroquinolones -which are the main therapeutic options- limits their treatment options. This study aimed to assess the local resistance patterns against different antimicrobials and to determine the extended-spectrum β-lactamase (ESBLs) producers. The study revealed that 36% of clinical isolates were ESBL producers, showing high resistance rates towards β-lactams and non-β-lactams, especially sulphamethoxazole-trimethoprim and fluoroquinolones. However, they were susceptible to chloramphenicol and doxycycline (33% and 20%; respectively). Also, the investigation aimed to screen the plasmid profile of quinolone-resistant ESBLs-producers and to detect the plasmid-mediated quinolone resistance genes including qnrA, qnrS, qnrB, qnrC, qnrD, and qnrVC. Moreover, the conjugative plasmid among the quinolone-resistant isolates was elucidated. The results showed that extracted plasmids of sizes ranging from ≈0.9 to 21.23 Kb, divided into 7 plasmid patterns were detected. A plasmid of approximately 21.23 Kb was found in all isolates and the QnrS gene was the most predominant gene. Moreover, the frequency of transconjugation within the same genus was higher than that recorded between different genera; where 68% of E. coli isolates transferred the resistance genes compared to Klebsiella isolates (36.6%). Plasmid profiles of transconjugants demonstrated great similarity, where 21.23 Kb plasmid was detected in all transconjugants. Since these transconjugants were quinolone-resistant ESBL producers, it has been suggested that quinolone resistance determinants might be carried on that plasmid.
{"title":"Investigation of plasmid-mediated quinolone resistance among extended-spectrum β-lactamase isolates of E. coli and K. pneumoniae","authors":"Ashraf A. Kadry, May A. El-Antrawy, Amira M. El-Ganiny","doi":"10.1038/s41429-024-00761-z","DOIUrl":"10.1038/s41429-024-00761-z","url":null,"abstract":"Escherichia coli and Klebsiella pneumoniae are important members of the Enterobacteriaceae family, involved in many infections. The increased resistance rate towards β-lactams and fluoroquinolones -which are the main therapeutic options- limits their treatment options. This study aimed to assess the local resistance patterns against different antimicrobials and to determine the extended-spectrum β-lactamase (ESBLs) producers. The study revealed that 36% of clinical isolates were ESBL producers, showing high resistance rates towards β-lactams and non-β-lactams, especially sulphamethoxazole-trimethoprim and fluoroquinolones. However, they were susceptible to chloramphenicol and doxycycline (33% and 20%; respectively). Also, the investigation aimed to screen the plasmid profile of quinolone-resistant ESBLs-producers and to detect the plasmid-mediated quinolone resistance genes including qnrA, qnrS, qnrB, qnrC, qnrD, and qnrVC. Moreover, the conjugative plasmid among the quinolone-resistant isolates was elucidated. The results showed that extracted plasmids of sizes ranging from ≈0.9 to 21.23 Kb, divided into 7 plasmid patterns were detected. A plasmid of approximately 21.23 Kb was found in all isolates and the QnrS gene was the most predominant gene. Moreover, the frequency of transconjugation within the same genus was higher than that recorded between different genera; where 68% of E. coli isolates transferred the resistance genes compared to Klebsiella isolates (36.6%). Plasmid profiles of transconjugants demonstrated great similarity, where 21.23 Kb plasmid was detected in all transconjugants. Since these transconjugants were quinolone-resistant ESBL producers, it has been suggested that quinolone resistance determinants might be carried on that plasmid.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 11","pages":"768-777"},"PeriodicalIF":2.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141876727","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 : 2024-08-01DOI: 10.1038/s41429-024-00757-9
Sheo B. Singh, James Occi, John Ondeyka, John F. Barrett, Prakash Masurekar, Mary Motyl, Charles Gill, Gino Salituro
Boxazomycins A-C are potent broad-spectrum antibiotics isolated from Actinomycetes strain G495-1 in 1987. We now report that boxazomycin A inhibits bacterial growth by selectively inhibiting protein synthesis, its effect is bacteriostatic, and it is equally active against drug resistant bacterial strains. No cross-resistance to protein synthesis inhibitors was observed suggesting that its inhibition is distinct from clinical protein synthesis inhibitors. We also report in vivo efficacy in a Staphylococcus aureus murine infection model supported by corresponding pharmacokinetic studies.
盒唑霉素 A-C 是 1987 年从放线菌菌株 G495-1 中分离出来的强效广谱抗生素。我们现在报告说，博azomycin A 通过选择性抑制蛋白质合成来抑制细菌生长，它具有抑菌作用，而且对耐药菌株同样有效。没有观察到对蛋白质合成抑制剂的交叉耐药性，这表明它的抑制作用不同于临床上的蛋白质合成抑制剂。我们还报告了在金黄色葡萄球菌小鼠感染模型中的体内疗效，并辅以相应的药代动力学研究。
{"title":"Antibacterial and mechanism of action studies of boxazomycin A","authors":"Sheo B. Singh, James Occi, John Ondeyka, John F. Barrett, Prakash Masurekar, Mary Motyl, Charles Gill, Gino Salituro","doi":"10.1038/s41429-024-00757-9","DOIUrl":"10.1038/s41429-024-00757-9","url":null,"abstract":"Boxazomycins A-C are potent broad-spectrum antibiotics isolated from Actinomycetes strain G495-1 in 1987. We now report that boxazomycin A inhibits bacterial growth by selectively inhibiting protein synthesis, its effect is bacteriostatic, and it is equally active against drug resistant bacterial strains. No cross-resistance to protein synthesis inhibitors was observed suggesting that its inhibition is distinct from clinical protein synthesis inhibitors. We also report in vivo efficacy in a Staphylococcus aureus murine infection model supported by corresponding pharmacokinetic studies.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 10","pages":"679-684"},"PeriodicalIF":2.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41429-024-00757-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141876726","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 : 2024-07-30DOI: 10.1038/s41429-024-00762-y
Richard Kriz, Kathrin Spettel, Alina Pichler, Katharina Schefberger, Maria Sanz-Codina, Felix Lötsch, Nicole Harrison, Birgit Willinger, Markus Zeitlinger, Heinz Burgmann, Heimo Lagler
Cefiderocol, a novel siderophore cephalosporin, demonstrates promising in vitro activity against multidrug-resistant Gram-negative bacteria, including carbapenemase-producing strains. Nonetheless, only a few reports are available regarding the acquisition of resistance in clinical settings, primarily due to its recent usage. This study aimed to investigate cefiderocol resistance using an in vitro resistance development model to gain insights into the underlying molecular resistance mechanisms. Cefiderocol susceptible reference strains (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa) and a clinical Acinetobacter baumannii complex isolate were exposed to increasing cefiderocol concentrations using a high-throughput resistance development model. Cefiderocol susceptibility testing was performed using broth microdilution. Whole-genome sequencing was employed to identify newly acquired resistance mutations. Our in vitro resistance development model led to several clones of strains exhibiting cefiderocol resistance, with MIC values 8-fold to 512-fold higher than initial levels. In total, we found 42 different mutations in 26 genes, of which 35 could be described for the first time. Putative loss-of-function mutations were detected in the envZ, tonB, and cirA genes in 13 out of 17 isolates, leading to a decrease in cefiderocol influx. Other potential resistance mechanisms included multidrug efflux pumps (baeS, czcS, nalC), antibiotic-inactivating enzymes (ampR, dacB), and target mutations in penicillin-binding-protein genes (mrcB). This study reveals new insights into underlying molecular resistance mechanisms against cefiderocol. While mutations leading to reduced influx via iron transporters was the most frequent resistance mechanism, we also detected several other novel resistance mutations causing cefiderocol resistance.
{"title":"In vitro resistance development gives insights into molecular resistance mechanisms against cefiderocol","authors":"Richard Kriz, Kathrin Spettel, Alina Pichler, Katharina Schefberger, Maria Sanz-Codina, Felix Lötsch, Nicole Harrison, Birgit Willinger, Markus Zeitlinger, Heinz Burgmann, Heimo Lagler","doi":"10.1038/s41429-024-00762-y","DOIUrl":"10.1038/s41429-024-00762-y","url":null,"abstract":"Cefiderocol, a novel siderophore cephalosporin, demonstrates promising in vitro activity against multidrug-resistant Gram-negative bacteria, including carbapenemase-producing strains. Nonetheless, only a few reports are available regarding the acquisition of resistance in clinical settings, primarily due to its recent usage. This study aimed to investigate cefiderocol resistance using an in vitro resistance development model to gain insights into the underlying molecular resistance mechanisms. Cefiderocol susceptible reference strains (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa) and a clinical Acinetobacter baumannii complex isolate were exposed to increasing cefiderocol concentrations using a high-throughput resistance development model. Cefiderocol susceptibility testing was performed using broth microdilution. Whole-genome sequencing was employed to identify newly acquired resistance mutations. Our in vitro resistance development model led to several clones of strains exhibiting cefiderocol resistance, with MIC values 8-fold to 512-fold higher than initial levels. In total, we found 42 different mutations in 26 genes, of which 35 could be described for the first time. Putative loss-of-function mutations were detected in the envZ, tonB, and cirA genes in 13 out of 17 isolates, leading to a decrease in cefiderocol influx. Other potential resistance mechanisms included multidrug efflux pumps (baeS, czcS, nalC), antibiotic-inactivating enzymes (ampR, dacB), and target mutations in penicillin-binding-protein genes (mrcB). This study reveals new insights into underlying molecular resistance mechanisms against cefiderocol. While mutations leading to reduced influx via iron transporters was the most frequent resistance mechanism, we also detected several other novel resistance mutations causing cefiderocol resistance.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 11","pages":"757-767"},"PeriodicalIF":2.1,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41429-024-00762-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141857229","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}
An actinomycete, designated strain CH9-7T, was isolated from the rhizosphere soil of Mangifera indica. The morphological and chemotaxonomic properties, such as the production of spiral spore chains and the presence of LL-diaminopimelic acid in the peptidoglycan, showed that it belongs to the genus Streptomyces. Based on the 16S rRNA gene analysis, it was confirmed that strain CH9-7T was a member of the genus Streptomyces and revealed 99.9% 16S rRNA gene sequence similarity to its closest relative strains, Streptomyces lydicus NBRC 13058 T and Streptomyces chattanoogensis NBRC 12754 T. Although the strain showed high 16S rRNA gene sequence similarity values, however, genome relatedness indexes exhibited that the average nucleotide identity based on the MUMmer (ANIm) algorithm, the average amino acid identity (AAI), and the digital DNA–DNA hybridization values between strain CH9-7T and its closest phylogenomic relatives were below the threshold values for delineation of a novel species, (ANIm ranging from 87.5 to 88.6, AAI ranging from 80.6 to 84.6, and dDDH ranging from 28.4 to 31.7), respectively. A taxonomic position of strain CH9-7T in the phylogenomic tree showed that the closest relative strain was S. lydicus NBRC 13058 T. The comparative phenotypic studies between strain CH9-7T and its closest relatives revealed that strain CH9-7T could be classified as a novel species of the genus Streptomyces. Thus, the name Streptomyces siderophoricus sp. nov. is proposed for the strain. The type strain is CH9-7T ( = TBRC 17833 T = NBRC 116426 T). The chemical investigation led to the isolation of four known compounds (compounds 1-4). Among these compounds, compound 1 was identified to be nocardamine, a promising bioactive substance.
{"title":"Description of Streptomyces siderophoricus sp. nov., a promising nocardamine-producing species isolated from the rhizosphere soil of Mangifera indica","authors":"Thitikorn Duangupama, Pattama Pittayakhajonwut, Chakapong Intaraudom, Chanwit Suriyachadkun, Sarin Tadtong, Nattakorn Kuncharoen, Ya-Wen He, Somboon Tanasupawat, Chitti Thawai","doi":"10.1038/s41429-024-00763-x","DOIUrl":"10.1038/s41429-024-00763-x","url":null,"abstract":"An actinomycete, designated strain CH9-7T, was isolated from the rhizosphere soil of Mangifera indica. The morphological and chemotaxonomic properties, such as the production of spiral spore chains and the presence of LL-diaminopimelic acid in the peptidoglycan, showed that it belongs to the genus Streptomyces. Based on the 16S rRNA gene analysis, it was confirmed that strain CH9-7T was a member of the genus Streptomyces and revealed 99.9% 16S rRNA gene sequence similarity to its closest relative strains, Streptomyces lydicus NBRC 13058 T and Streptomyces chattanoogensis NBRC 12754 T. Although the strain showed high 16S rRNA gene sequence similarity values, however, genome relatedness indexes exhibited that the average nucleotide identity based on the MUMmer (ANIm) algorithm, the average amino acid identity (AAI), and the digital DNA–DNA hybridization values between strain CH9-7T and its closest phylogenomic relatives were below the threshold values for delineation of a novel species, (ANIm ranging from 87.5 to 88.6, AAI ranging from 80.6 to 84.6, and dDDH ranging from 28.4 to 31.7), respectively. A taxonomic position of strain CH9-7T in the phylogenomic tree showed that the closest relative strain was S. lydicus NBRC 13058 T. The comparative phenotypic studies between strain CH9-7T and its closest relatives revealed that strain CH9-7T could be classified as a novel species of the genus Streptomyces. Thus, the name Streptomyces siderophoricus sp. nov. is proposed for the strain. The type strain is CH9-7T ( = TBRC 17833 T = NBRC 116426 T). The chemical investigation led to the isolation of four known compounds (compounds 1-4). Among these compounds, compound 1 was identified to be nocardamine, a promising bioactive substance.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 11","pages":"737-745"},"PeriodicalIF":2.1,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762726","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 : 2024-07-11DOI: 10.1038/s41429-024-00760-0
Feffiana M. Amin, Enjuro Harunari, Naoya Oku, Yasuhiro Igarashi
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.
{"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}
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.
{"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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：