Noha Anwar Hassuna, Eman M. Rabea, W. K. M. Mahdi, Wedad M. Abdelraheem
{"title":"Biofilm formation and antimicrobial resistance pattern of uropathogenic E. coli ST131 isolated from children with malignant tumors","authors":"Noha Anwar Hassuna, Eman M. Rabea, W. K. M. Mahdi, Wedad M. Abdelraheem","doi":"10.1038/s41429-024-00704-8","DOIUrl":"10.1038/s41429-024-00704-8","url":null,"abstract":"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.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 5","pages":"324-330"},"PeriodicalIF":3.3,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41429-024-00704-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140029624","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":"Capability of a large bacterial artificial chromosome clone harboring multiple biosynthetic gene clusters for the production of diverse compounds","authors":"Kei Kudo, Takehiro Nishimura, Miho Izumikawa, Ikuko Kozone, Junko Hashimoto, Manabu Fujie, Hikaru Suenaga, Haruo Ikeda, Nori Satoh, Kazuo Shin-ya","doi":"10.1038/s41429-024-00711-9","DOIUrl":"10.1038/s41429-024-00711-9","url":null,"abstract":"The biosynthetic gene clusters (BGCs) for the macrocyclic lactone-based polyketide compounds are extremely large-sized because the polyketide synthases that generate the polyketide chains of the basic backbone are of very high molecular weight. In developing a heterologous expression system for the large BGCs amenable to the production of such natural products, we selected concanamycin as an appropriate target. We obtained a bacterial artificial chromosome (BAC) clone with a 211-kb insert harboring the entire BGC responsible for the biosynthesis of concanamycin. Heterologous expression of this clone in a host strain, Streptomyces avermitilis SUKA32, permitted the production of concanamycin, as well as that of two additional aromatic polyketides. Structural elucidation identified these additional products as ent-gephyromycin and a novel compound that was designated JBIR-157. We describe herein sequencing and expression studies performed on these BGCs, demonstrating the utility of large BAC clones for the heterologous expression of cryptic or near-silent loci.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 5","pages":"288-298"},"PeriodicalIF":3.3,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41429-024-00711-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140029625","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}
Belén R. Imperiale, María B. Mancino, Roberto D. Moyano, Silvia de la Barrera, Nora S. Morcillo
{"title":"In vitro and ex vivo activity of the fluoroquinolone DC-159a against mycobacteria","authors":"Belén R. Imperiale, María B. Mancino, Roberto D. Moyano, Silvia de la Barrera, Nora S. Morcillo","doi":"10.1038/s41429-024-00709-3","DOIUrl":"10.1038/s41429-024-00709-3","url":null,"abstract":"Antimicrobial resistance is a global health problem. In 2021, it was estimated almost half a million of multidrug-resistant tuberculosis (MDR-TB) cases. Besides, non-tuberculous mycobacteria (NTM) are highly resistant to several drugs and the emergence of fluoroquinolone (FQ) resistant M. tuberculosis (Mtb) is also a global concern making treatments difficult and with variable outcome. The aim of this study was to evaluate the activity of the FQ, DC-159a, against Mtb and NTM and to explore the cross-resistance with the currently used FQs. A total of 12 pre-extensively drug-resistant (XDR) Mtb, 2 XDR, 36 fully drug susceptible strains and 41 NTM isolates were included to estimate the in vitro activity of DC-159a, moxifloxacin (MOX) and levofloxacin (LX), using minimal inhibitory and bactericidal concentration (MIC and MBC). The activity inside the human macrophages and pulmonary epithelial cells were also determined. DC-159a was active in vitro and ex vivo against mycobacteria. Besides, it was more active than MOX/LX. Moreover, no cross-resistance was evidenced between DC-159a and LX/MOX as DC-159a could inhibit Mtb and MAC strains that were already resistant to LX/MOX. DC-159a could be a possible candidate in new therapeutic regimens for MDR/ XDR-TB and mycobacterioses cases.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 5","pages":"306-314"},"PeriodicalIF":3.3,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140029552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Proansamycin B derivatives from the post-PKS modification gene deletion mutant of Amycolatopsis mediterranei S699","authors":"Xinyu Ma, Feng Ye, Xiaochun Zhang, Zhan Li, Yanjiao Ding, Chunhua Lu, Yuemao Shen","doi":"10.1038/s41429-024-00708-4","DOIUrl":"10.1038/s41429-024-00708-4","url":null,"abstract":"Ten new proansamycin B congeners (1–10) together with one known (11) were isolated and characterized on the basis of 1D and 2D NMR spectroscopic and HRESIMS data from the Amycolatopsis mediterranei S699 ΔPM::rifR+rif-orf19 mutant. Compounds 8 and 9 featured with six-membered ring and five-membered ring hemiketal, respectively. Compounds 1, 2, and 9 displayed antibacterial activity against MRSA (methicillin-resistant Staphylococcus aureus), with the MIC (minimal inhibitory concentration) values of 64, 8, and 128 µg/mL, respectively. Compound 1 showed significant cytotoxicity against MDA-MB-231, HepG2 and Panc-1 cell lines with IC50 (half maximal inhibitory concentration) values of 2.3 ± 0.2, 2.5 ± 0.3 and 3.8 ± 0.5 μM, respectively.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 5","pages":"278-287"},"PeriodicalIF":3.3,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41429-024-00708-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139974691","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":"Actinobacterial chalkophores: the biosynthesis of hazimycins","authors":"Kenichi Matsuda, Hiroto Maruyama, Kumiko Imachi, Haruo Ikeda, Toshiyuki Wakimoto","doi":"10.1038/s41429-024-00706-6","DOIUrl":"10.1038/s41429-024-00706-6","url":null,"abstract":"Copper is a transition metal element with significant effects on the morphological development and secondary metabolism of actinobacteria. In some microorganisms, copper-binding natural products are employed to modulate copper homeostasis, although their significance in actinobacteria remains largely unknown. Here, we identified the biosynthetic genes of the diisocyanide natural product hazimycin in Kitasatospora purpeofusca HV058, through gene knock-out and heterologous expression. Biochemical analyses revealed that hazimycin A specifically binds to copper, which diminishes its antimicrobial activity. The presence of a set of putative importer/exporter genes surrounding the biosynthetic genes suggested that hazimycin is a chalkophore that modulates the intracellular copper level. A bioinformatic survey of homologous gene cassettes, as well as the identification of two previously unknown hazimycin-producing Streptomyces strains, indicated that the isocyanide-based mechanism of copper homeostasis is prevalent in actinobacteria.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 4","pages":"228-237"},"PeriodicalIF":3.3,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41429-024-00706-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139914071","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}
So-ichiro Kimura, Yoshihiro Watanabe, Yudai Mikasa, Rei Miyano, Toshiyuki Tokiwa, Kenichi Nonaka, Takuji Nakashima, Yoshihiko Noguchi, Tomoyasu Hirose, Toshiaki Sunazuka, Rei Hokari, Aki Ishiyama, Masato Iwatsuki
{"title":"Virgaricins C and D, new pramanicin analogs produced by Apiospora sp. FKI-8058","authors":"So-ichiro Kimura, Yoshihiro Watanabe, Yudai Mikasa, Rei Miyano, Toshiyuki Tokiwa, Kenichi Nonaka, Takuji Nakashima, Yoshihiko Noguchi, Tomoyasu Hirose, Toshiaki Sunazuka, Rei Hokari, Aki Ishiyama, Masato Iwatsuki","doi":"10.1038/s41429-023-00699-8","DOIUrl":"10.1038/s41429-023-00699-8","url":null,"abstract":"Two new pramanicin analogs, named virgaricins C (1) and D (2), were discovered by physicochemical screening from a static cultured material of Apiospora sp. FKI-8058. Their structures were elucidated by MS and NMR analyses and chemical derivatization. Compounds 1 and 2 showed moderate antimalarial activity and cytotoxicity.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 4","pages":"206-213"},"PeriodicalIF":3.3,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139665469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Author Index for Volume 76","authors":"","doi":"10.1038/s41429-023-00682-3","DOIUrl":"10.1038/s41429-023-00682-3","url":null,"abstract":"","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 2","pages":"129-132"},"PeriodicalIF":3.3,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139572063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Substance Index for Volumne 76","authors":"","doi":"10.1038/s41429-023-00676-1","DOIUrl":"10.1038/s41429-023-00676-1","url":null,"abstract":"","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 2","pages":"133-133"},"PeriodicalIF":3.3,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41429-023-00676-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139572066","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":"Antibacterial p-terphenyl and α‑pyrone derivates isolated from the marine-derived actinomycete Nocardiopsis sp. HDN154086","authors":"Luning Zhou, Yimin Chang, Shengkuan Yang, Xiaofei Huang, Jiaxiang Wang, Chengyu Jiang, Tianjiao Zhu, Dehai Li, Qian Che","doi":"10.1038/s41429-023-00698-9","DOIUrl":"10.1038/s41429-023-00698-9","url":null,"abstract":"Assisted by OSMAC strategy, one new p-terphenyl and two new α‑pyrone derivates, namely nocarterphenyl I (1) and nocardiopyrone D–E (2–3), were obtained and characterized from the marine sediment-derived actinomycete Nocardiopsis sp. HDN154086. The structures of these compounds were determined on the basis of MS, NMR spectroscopic data and single-crystal X-ray diffraction. Compound 1 with a rare 2,2’-bithiazole structure among natural products showed promising activity against five bacteria with MIC values ranging from 0.8 to 1.6 μM and 3 exhibited notable antibacterial activity against MRSA compared the positive control ciprofloxacin.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 4","pages":"201-205"},"PeriodicalIF":3.3,"publicationDate":"2024-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139560459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Synthesis and biological evaluation of nectriatide derivatives, potentiators of amphotericin B activity","authors":"Kenichiro Nagai, Keisuke Kobayashi, Ryosuke Miyake, Yukino Sato, Reiko Seki, Takashi Fukuda, Akiho Yagi, Ryuji Uchida, Taichi Ohshiro, Hiroshi Tomoda","doi":"10.1038/s41429-023-00700-4","DOIUrl":"10.1038/s41429-023-00700-4","url":null,"abstract":"Nectriatide 1a, a naturally occurring cyclic tetrapeptide, has been reported to a potentiator of amphotericin B (AmB) activity. In order to elucidate its structure-activity relationships, we synthesized nectriatide derivatives with different amino acids in solution-phase synthesis and evaluated AmB-potentiating activity against Candida albicans. Among them, C-and N-terminal protected linear peptides were found to show the most potent AmB-potentiating activity.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 4","pages":"214-220"},"PeriodicalIF":3.3,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41429-023-00700-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139546933","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}