Journal of Antibiotics最新文献

A novel clotrimazole selenium nano-composite for combating deep dermal Candida albicans infections and virulence genes. 一种新型克霉唑硒纳米复合材料对抗皮肤深层白色念珠菌感染和毒力基因。

IF 2.1 4区医学

Journal of Antibiotics Pub Date : 2025-05-29 DOI: 10.1038/s41429-025-00831-w

Rana Eshimy, Ahmed I El-Batal, Farag M Mosallam

{"title":"A novel clotrimazole selenium nano-composite for combating deep dermal Candida albicans infections and virulence genes.","authors":"Rana Eshimy, Ahmed I El-Batal, Farag M Mosallam","doi":"10.1038/s41429-025-00831-w","DOIUrl":"https://doi.org/10.1038/s41429-025-00831-w","url":null,"abstract":"Traditional antifungal drugs are ineffective against multidrug-resistant Candida infections. The goal of this work is the preparation of Clotrimazole Selenium Nano-composite (CZ-Se-NC) suspension and CZ-Se-NC-gel for combating clotrimazole-resistant Candida albicans (NCRRT-CZR) infection. CZ-Se-NC is prepared by simple homogenization ultra-sonication technique and validated by SEM-EDX mapping, DLS, Zeta potential and FT-IR that confirm formulation of Nano-composite. In vitro results demonstrated that CZ-Se-NC and formulated CZ-Se-NC gel have the same anti-candidal activity showing inhibitory zone values 31.0 ± 0.931 mm, 27.0 ± 1.004 and MIC values 0.625, 1.25 µg ml-1 and MFC values 2.5, 5 µg ml-1 against C. albicans (ATCC 10231) and C. albicans (NCRRT-CZR), respectively. Non-treated C. albicans (NCRRT-CZR) show biofilm formation 100% that become 8.62% after treatment with CZ-Se-NC at 1/2MIC. Virulence genes ALS1, Plb1, CDR1 and ERG11 expression of C. albicans (NCRRT-CZR) were down regulated by 76.67, 87.06, 53.67 and 76.01%, respectively, after treatment with CZ-Se-NC. The CZ-Se-NC gel formula gradually releases clotrimazole and selenium 41 and 48% after 24 h, respectively. Furthermore, after deep dermal infections by C. albicans (NCRRT-CZR), treated mice exhibit excellent skin infection healing performance as evidenced by the significantly reduced inflammation and complete skin infection clearance after treatment with CZ-Se-NC gel. Gamma rays show a negative impact on the CZ-Se-NC size distribution. The formulation of CZ-Se-NC as a topical gel formulation could provide an opportunity to develop a cost-effective approach to achieve optimal therapeutic performance against resistant fungal infections at a much lower dose than is currently used. Additionally, it will enhance patient compliance by reducing the frequent application.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144183225","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}

引用次数: 0

Isolation and synthesis of a new cyclic tetrapeptide from marine-associated Bacillus sp. and its bacterial biofilm formation inhibitory activity. 海洋相关芽孢杆菌新环四肽的分离合成及其抑菌活性研究。

IF 2.1 4区医学

Journal of Antibiotics Pub Date : 2025-05-19 DOI: 10.1038/s41429-025-00830-x

Shuaiqi Ma, Shixin Li, Li Song, Asma Riaz, Ruifeng Huang, Shaofen Zhou, Jingnan Qiu, Zonglin Chu, Jian He

引用次数: 0

Unlocking hidden bioactive compounds: from indolocarbazole and RiPP biosynthesis to the activation of cryptic secondary metabolism via microbial interactions. 解锁隐藏的生物活性化合物：从吲哚咔唑和RiPP生物合成到通过微生物相互作用激活隐次生代谢。

IF 2.1 4区医学

Journal of Antibiotics Pub Date : 2025-05-16 DOI: 10.1038/s41429-025-00828-5

Hiroyasu Onaka

{"title":"Unlocking hidden bioactive compounds: from indolocarbazole and RiPP biosynthesis to the activation of cryptic secondary metabolism via microbial interactions.","authors":"Hiroyasu Onaka","doi":"10.1038/s41429-025-00828-5","DOIUrl":"https://doi.org/10.1038/s41429-025-00828-5","url":null,"abstract":"Actinomycetes, particularly Streptomyces, are soil microorganisms that produce diverse secondary metabolites with pharmaceutical applications, such as antibiotics and anticancer drugs. These metabolites play important roles in microbial competition and survival. This review highlights three major aspects of actinomycete secondary metabolism: (1) the biosynthesis of indolocarbazoles, (2) the biosynthesis of RiPPs (ribosomally synthesized and post-translationally modified peptides), and (3) the activation of secondary metabolism through microbial interactions. Indolocarbazoles, including staurosporine and rebeccamycin, are potent inhibitors of kinases and DNA topoisomerase I, with potential as anticancer agents. Their biosynthetic pathways involve multiple enzymatic steps, notably carbon-carbon bond formation catalyzed by cytochrome P450 enzymes. RiPPs such as goadsporin and lactazole are highly modular peptide natural products; structural gene modification enables the generation of diverse analogs. A cell-free one-pot synthesis platform has been developed for efficient analog production. To activate cryptic biosynthetic pathways, we employed a combined-culture strategy using actinomycetes and mycolic acid-containing bacteria, resulting in the discovery of 42 novel compounds. Genetic and physiological data indicate that physical contact, rather than diffusible signaling, is essential for induction. These insights emphasize the importance of microbial interactions in natural product biosynthesis and offer new directions for drug discovery through synthetic biology and microbial ecology.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086986","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}

引用次数: 0

Antibacterial properties of quaternized cellulose nanocrystals in clinical isolates of multidrug-resistant gram-negative bacteria. 季铵化纤维素纳米晶体在临床分离多重耐药革兰氏阴性菌中的抗菌性能。

IF 2.1 4区医学

Journal of Antibiotics Pub Date : 2025-05-15 DOI: 10.1038/s41429-025-00829-4

Dong Kwon, Nadarajah Vasanthan, Noor Ibrahim, Noel Yahra

{"title":"Antibacterial properties of quaternized cellulose nanocrystals in clinical isolates of multidrug-resistant gram-negative bacteria.","authors":"Dong Kwon, Nadarajah Vasanthan, Noor Ibrahim, Noel Yahra","doi":"10.1038/s41429-025-00829-4","DOIUrl":"https://doi.org/10.1038/s41429-025-00829-4","url":null,"abstract":"Gram-negative bacterial pathogens are responsible for various infections. Over the past decade, these pathogens have acquired resistance to multiple antibiotics, and the multidrug-resistant (MDR) bacteria have rapidly spread globally, creating significant treatment challenges. Quaternized cellulose nanocrystals (CNCs) have promising antibacterial properties. We previously reported quaternized CNCs with ten-carbon (CNC-3) and sixteen-carbon (CNC-4) alkyl chains and an unmodified CNC (CNC-1). We found that CNC-4 exhibited a significant bactericidal effect against Staphylococcus aureus. In this study, we aim to evaluate the antibacterial properties of the quaternized CNCs against Gram-negative MDR clinical isolates of Acinetobacter baumannii (21 isolates), Klebsiella pneumoniae (18 isolates), and Escherichia coli (7 isolates), including each of their reference species. Agar diffusion, minimum bactericidal concentration (MBC), and bacterial killing pattern were conducted. The results showed that CNC-3 exhibited an MBC of 50 μg ml-1 for 28% (13 out of 46 isolates) and 100 μg ml-1 for 72% (33 out of 46 isolates), regardless of their antibiotic susceptibility. In comparison, CNC-4 exhibited an MBC of 100 μg ml-1 for 28% (5 out of 18 K. pneumoniae), while all other isolates and the reference species exhibited an MBC of >100 μg ml-1. For CNC-1, the MBC was >100 μg ml-1 for all tested isolates and the reference species. These results suggest that, unlike S. aureus, CNC-3 has a significantly higher and broader spectrum of bactericidal effects than CNC-4 against Gram-negative bacteria. This finding suggests that quaternized CNCs may be a potential antimicrobial agent for treating Gram-negative bacterial infections.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081752","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}

引用次数: 0

Contezolid, a novel oxazolidinone antibiotic, acts as a potential anti-inflammatory agent. 康替唑胺是一种新型的恶唑烷类抗生素，具有潜在的抗炎作用。

IF 2.1 4区医学

Journal of Antibiotics Pub Date : 2025-05-01 Epub Date: 2025-05-09 DOI: 10.1038/s41429-025-00825-8

Lu Liu, Junsheng Chen, Yajie Deng, Fei Gao, Ting Lin, Zhijun Yang, Daijie Chen, Yu Yin

{"title":"Contezolid, a novel oxazolidinone antibiotic, acts as a potential anti-inflammatory agent.","authors":"Lu Liu, Junsheng Chen, Yajie Deng, Fei Gao, Ting Lin, Zhijun Yang, Daijie Chen, Yu Yin","doi":"10.1038/s41429-025-00825-8","DOIUrl":"10.1038/s41429-025-00825-8","url":null,"abstract":"Contezolid, a novel oxazolidinone antibiotic, has comparable or superior antibacterial efficacy and safety to linezolid, now widely used for treating multidrug-resistant Gram-positive bacterial infections. Although numerous studies have investigated the immunomodulatory effects of oxazolidinone antibiotics, the immunomodulatory properties of contezolid remain poorly understood. This study aimed to investigate the anti‑inflammatory effects of contezolid using LPS-stimulated RAW264.7 macrophages. Experimental assessments demonstrated that contezolid significantly suppressed key inflammatory mediators, including nitric oxide and reactive oxygen species, while reducing IL-6 and TNF-α cytokine levels and CD86 concurrently. Functional analysis revealed attenuated phagocytic activity through fluorescence-based bacterial internalization assays and viable bacterial colony counting. Mechanistic studies using qRT-PCR identified transcriptional downregulation of Toll-like receptors, with TLR2 showing particularly pronounced suppression compared to activated controls. These findings indicate that, in addition to its known antimicrobial activity, contezolid also exhibits anti-inflammatory properties.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":" ","pages":"384-387"},"PeriodicalIF":2.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019270","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}

引用次数: 0

New dimeric 5-hydroxy-2-hexenoic acid isolated from culture broth of Clonostachys rogersoniana. 新二聚体5-羟基-2-己烯酸的分离。

IF 2.1 4区医学

Journal of Antibiotics Pub Date : 2025-05-01 Epub Date: 2025-04-24 DOI: 10.1038/s41429-025-00824-9

Dae-Cheol Choi, Dae-Won Ki, Yoon Hee Kim, Min-Ju Park, Ji-Yul Kim, In-Kyoung Lee, Bong-Sik Yun

引用次数: 0

In vitro synergistic effect and mutant prevention concentration of eravacycline alone or in combination with various antibiotics against OXA-48 producing enterobacterales. 依拉瓦环素单用或联用多种抗生素对产OXA-48肠杆菌的体外协同效应及突变预防浓度

IF 2.1 4区医学

Journal of Antibiotics Pub Date : 2025-05-01 Epub Date: 2025-05-07 DOI: 10.1038/s41429-025-00823-w

Bekir Özer, Emel Mataraci Kara, Berna Özbek Çelik

{"title":"In vitro synergistic effect and mutant prevention concentration of eravacycline alone or in combination with various antibiotics against OXA-48 producing enterobacterales.","authors":"Bekir Özer, Emel Mataraci Kara, Berna Özbek Çelik","doi":"10.1038/s41429-025-00823-w","DOIUrl":"10.1038/s41429-025-00823-w","url":null,"abstract":"This study examines the effects of combining eravacycline with various antibiotics on carbapenem-resistant Enterobacterales (CRE) isolated from bloodstream infections. Fifty Enterobacterales isolates that produce the OXA-48 enzyme were tested for their Minimum Inhibitory Concentrations (MICs) using broth microdilution. The Mutant Prevention Concentrations (MPCs) of eravacycline, tigecycline, levofloxacin, colistin, fosfomycin, meropenem, and tobramycin were evaluated against CRE isolates. The bactericidal and synergistic effects of eravacycline, alone or in combination with other antibiotics, were assessed using time-kill curve (TKC) experiments. The in vitro synergistic activities of tested antibiotics in combination with eravacycline were also determined by microbroth checkerboard technique, and results were interpreted using the fractional inhibitory concentration (FIC) index. The results of our study demonstrated that colistin exhibited the best bactericidal activity and the highest susceptibility rates among the evaluated strains. Eravacycline exhibited lower MPC values compared to tigecycline when used alone. The results of the TCK method showed that the most effective synergistic interactions were observed when eravacycline was combined with levofloxacin, colistin, or meropenem. The results obtained by microbroth checkerboard techniques also described synergistic activity with all tested eravacycline combinations against tested clinical isolates of Enterobacterales. No antagonism was detected. The study's results indicate that the combination of eravacycline with colistin, meropenem, tobramycin or levofloxacin showed synergistic activity against strains of Enterobacterales that produce OXA-48. This combination therapy may be a viable alternative for treating carbapenemase-producing Enterobacterales bacteria. In addition, eravacycline's lower MPC value suggests it may avoid the emergence of resistant mutant strains in the population.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":" ","pages":"370-379"},"PeriodicalIF":2.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144052952","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}

引用次数: 0

Biosynthesis of antibiotics with sulfonamide and azaindane moieties. 磺胺和氮杂丹类抗生素的生物合成。

IF 2.1 4区医学

Journal of Antibiotics Pub Date : 2025-05-01 Epub Date: 2025-04-07 DOI: 10.1038/s41429-025-00819-6

Takayoshi Awakawa

引用次数: 0

Novel bifunctional antibacterial peptides mediated by a covalent conjugation strategy combat priority multidrug-resistant gram-negative pathogens through dual targets. 由共价偶联策略介导的新型双功能抗菌肽通过双靶点对抗优先多重耐药革兰氏阴性病原体。

IF 2.1 4区医学

Journal of Antibiotics Pub Date : 2025-05-01 Epub Date: 2025-04-23 DOI: 10.1038/s41429-025-00822-x

Yanan Li, Haoran Mei, Yuanzhen Dong, Jianguang Lu, Xiaoqian Yang, Ying Zhang, Meiqing Feng, Jun Feng

{"title":"Novel bifunctional antibacterial peptides mediated by a covalent conjugation strategy combat priority multidrug-resistant gram-negative pathogens through dual targets.","authors":"Yanan Li, Haoran Mei, Yuanzhen Dong, Jianguang Lu, Xiaoqian Yang, Ying Zhang, Meiqing Feng, Jun Feng","doi":"10.1038/s41429-025-00822-x","DOIUrl":"10.1038/s41429-025-00822-x","url":null,"abstract":"The escalating antibiotic resistance presents formidable challenges in the treatment of Gram-negative bacterial infections. Clinically, these bacteria have also acquired resistance to polymyxin, the last resort of defense. Novel antibiotics with a single mode of action are susceptible to rapid resistance development, and sometimes asynchronous pharmacokinetics also hinders the effectiveness of combined administration strategies in vivo. Here, we developed a class of novel bifunctional antibacterial peptides by covalently conjugating a series of modified PbgA-derived peptides with colistin analog (PE-2C-C8-DH) via a small-molecule linker (KCM02). These bifunctional peptides show remarkable synergistic antibacterial efficacy, where \"1 + 1 > 2\", against various priority multidrug-resistant Gram-negative bacteria, involving polymyxin-resistant strains. By optimizing the structure-activity relationship, two compounds (BP-28 and BP-37) with distinct activity preferences were obtained, which possess rapid bactericidal efficacy and a significantly lower risk of resistance compared to single-mode-of-action antibacterial agents, without hemolytic toxicity and cytotoxicity. Identification of antibacterial targets revealed that they can damage Gram-negative bacterial membrane by targeting LPS and BamA. Our study offers a referable approach for the development of novel antimicrobial agents.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":" ","pages":"359-369"},"PeriodicalIF":2.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144034952","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}

引用次数: 0

Evaluation of lung epithelial lining fluid concentrations of lascufloxacin against Streptococcus pneumoniae in a hollow-fiber infection model. 中空纤维感染模型肺上皮内层液拉库沙星抗肺炎链球菌浓度的评价

IF 2.1 4区医学

Journal of Antibiotics Pub Date : 2025-05-01 Epub Date: 2025-05-07 DOI: 10.1038/s41429-025-00826-7

Haruka Nakagawa Kamura, Tetsuo Yamaguchi, Toshihiro Kasama, Yukitaka Hayashi, Masakaze Hamada, Kazuaki Matsumoto, Ryo Miyake, Yoshikazu Ishii

引用次数: 0