Journal of Antibiotics最新文献_第7页

Anti-MRSA activity of chlorophenyl pyrrolo benzodiazepines compound 氯苯基吡咯并二氮杂卓化合物的抗 MRSA 活性。

IF 2.1 4区医学

Journal of Antibiotics Pub Date : 2024-06-18 DOI: 10.1038/s41429-024-00747-x

Suresh K. Mondal, Sk Aftabul Alam, Gourisankar Roymahapatra, Santi M. Mandal

{"title":"Anti-MRSA activity of chlorophenyl pyrrolo benzodiazepines compound","authors":"Suresh K. Mondal, Sk Aftabul Alam, Gourisankar Roymahapatra, Santi M. Mandal","doi":"10.1038/s41429-024-00747-x","DOIUrl":"10.1038/s41429-024-00747-x","url":null,"abstract":"Antibiotic resistant is the major concern in public health to control the infectious diseases. MRSA (Methicillin-resistant Staphylococcus aureus) is a significant concern in healthcare settings due to its resistance to many antibiotics, including methicillin and other beta-lactams. MRSA infection difficult to treat and increases the risk of complications. Here, we have tested a series of highly condensed heterocyclic derivatives of pyrrolo[1,2-a][1,4]benzodiazepines. Compounds were tested against both, Gram-positive bacteria, Staphylococcus aureus and S. epidermidis, and Gram-negative bacteria, Escherichia coli and Pseudomonas aeruginosa, to assess the antimicrobial efficacy. Compared to Gram-negative bacteria, compounds showed much stronger antibacterial activity against Gram-positive bacteria. SM-5 [Ethyl2-(7-(4-chlorophenyl)-4-methoxy-6,7,8,13-tetrahydro-5H-benzo[e]benzo[5,6][1,4]diazepino[2,1-a]isoindol-15-yl)acetate] derivative was selected as best on the basis of higher therapeutic index among the tested compounds, showed MIC value of 7.81 µg. ml−1 against Staphylococcus strains. Molecular docking analysis between cell wall biosynthesis protein of S. aureus and SM-5 revealed that PBP2a showed the highest binding energy (−8.3 Kcal mol−1), followed by beta-lactam-inducible PBP4 (−7.7 Kcal mol−1), and lipoteichoic acid synthase (−7.5 Kcal mol−1) which is comparably higher than methicillin. Ground state energy calculations by DFT analysis revealed that compound SM-5 and SM-6, almost have equal electronegativity 0.11018 au which also satisfy the quality of the compound reactivity. Analysis of their biofilm inhibition in vitro and in silico toxicity analysis demonstrated their substantial potential to be a kind of future lead antibiotic.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 9","pages":"589-599"},"PeriodicalIF":2.1,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421886","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

Synthesis and antibacterial action of 3’,6’-disubstituted spectinomycins 3',6'-二取代的光谱霉素的合成和抗菌作用。

IF 2.1 4区医学

Journal of Antibiotics Pub Date : 2024-06-18 DOI: 10.1038/s41429-024-00750-2

Suresh Dharuman, Gregory A. Phelps, Christine M. Dunn, Laura A. Wilt, Patricia A. Murphy, Robin B. Lee, Hannah E. Snoke, Petra Selchow, Klara Haldimann, Erik C. Böttger, Sven N. Hobbie, Peter Sander, Richard E. Lee

{"title":"Synthesis and antibacterial action of 3’,6’-disubstituted spectinomycins","authors":"Suresh Dharuman, Gregory A. Phelps, Christine M. Dunn, Laura A. Wilt, Patricia A. Murphy, Robin B. Lee, Hannah E. Snoke, Petra Selchow, Klara Haldimann, Erik C. Böttger, Sven N. Hobbie, Peter Sander, Richard E. Lee","doi":"10.1038/s41429-024-00750-2","DOIUrl":"10.1038/s41429-024-00750-2","url":null,"abstract":"Spectinomycin is an aminocyclitol antibiotic with a unique ribosomal binding site. Prior synthetic modifications of spectinomycin have enhanced potency and antibacterial spectrum through addition at the 6’-position to produce trospectomycin and to the 3’-position to produce spectinamides and aminomethyl spectinomycins. This study focused on the design, synthesis, and evaluation of three 3’,6’-disubstituted spectinomycin analogs: trospectinamide, N-benzyl linked aminomethyl, and N-ethylene linked aminomethyl trospectomycins. Computational experiments predicted that these disubstituted analogs would be capable of binding within the SPC ribosomal binding site. The new analogs were synthesized from trospectomycin, adapting the previously established routes for the spectinamide and aminomethyl spectinomycin series. In a cell-free translation assay, the disubstituted analogs showed ribosomal inhibition similar to spectinomycin or trospectomycin. These disubstituted analogs demonstrated inhibitory MIC activity against various bacterial species with the 3’-modification dictating spectrum of activity, leading to improved activity against mycobacterium species. Notably, N-ethylene linked aminomethyl trospectomycins exhibited increased potency against Mycobacterium abscessus and trospectinamide displayed robust activity against M. tuberculosis, aligning with the selective efficacy of spectinamides. The study also found that trospectomycin is susceptible to efflux in M. tuberculosis and M. abscessus. These findings contribute to the understanding of the structure-activity relationship of spectinomycin analogs and can guide the design and synthesis of more effective spectinomycin compounds.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 9","pages":"577-588"},"PeriodicalIF":2.1,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41429-024-00750-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421900","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}

引用次数: 0

Reversal of carbapenem resistance in Pseudomonas aeruginosa by camelid single domain antibody fragment (VHH) against the C4-dicarboxylate transporter 驼科动物针对 C4-二羧酸盐转运体的单域抗体片段（VHH）可逆转铜绿假单胞菌对碳青霉烯类药物的耐药性。

IF 2.1 4区医学

Journal of Antibiotics Pub Date : 2024-06-17 DOI: 10.1038/s41429-024-00748-w

Anil Kumar Nagraj, Manjiri Shukla, Mansi Kulkarni, Pratik Patil, Mrunal Borgave, Sanjiban K. Banerjee

{"title":"Reversal of carbapenem resistance in Pseudomonas aeruginosa by camelid single domain antibody fragment (VHH) against the C4-dicarboxylate transporter","authors":"Anil Kumar Nagraj, Manjiri Shukla, Mansi Kulkarni, Pratik Patil, Mrunal Borgave, Sanjiban K. Banerjee","doi":"10.1038/s41429-024-00748-w","DOIUrl":"10.1038/s41429-024-00748-w","url":null,"abstract":"Antimicrobial resistance is emerging as the new healthcare crisis necessitating the development of newer classes of drugs using non-traditional approaches. Pseudomonas aeruginosa, one of the most common pathogens involved in nosocomial infections, is extremely difficult to treat even with the last resort frontline drug, the carbapenems. As the pathogen has the ability to acquire resistance to new small-molecule antibiotics, being deployed, a novel biological approach has been tried using antibody fragments in combination with carbapenems and β-lactams as adjunct therapy for an enduring solution to the problem. In this study, we developed a camelid antibody fragment (VHH) library against P. aeruginosa and isolated a highly potent hit, PsC23. Mass spectrometry identified the target to be a component of the C4-dicarboxylate transporter that feeds metabolites to the glyoxylate shunt particularly under conditions of oxidative stress. PsC23 is bacteriostatic at a concentration of 1.66 µM (25 µg ml−1) and shows a synergistic effect with both the classes of drugs at an effective concentration of 100–200 nM (1.5–3.0 µg ml−1) when co administered with them. In combination with meropenem the VHH completely cleared the infection from a neutropenic mouse with a carbapenem-resistant P. aeruginosa systemic infection. Blocking the glyoxylate shunt by PsC23 resulted in disruption of energy transduction due to a respiratory shift to the oxygen-depleted TCA cycle causing inhibition of efflux and increased free radical generation from carbapenems and β-lactams exerting a strong bactericidal effect that reversed the resistance to multiple unrelated drugs.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 9","pages":"612-626"},"PeriodicalIF":2.1,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421887","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

From inside to outside: exploring extracellular antimicrobial histone-derived peptides as multi-talented molecules 从内到外：探索细胞外抗菌组蛋白衍生肽这一多才多艺的分子。

IF 2.1 4区医学

Journal of Antibiotics Pub Date : 2024-06-13 DOI: 10.1038/s41429-024-00744-0

Carolina Muñoz-Camargo, Juan C. Cruz

{"title":"From inside to outside: exploring extracellular antimicrobial histone-derived peptides as multi-talented molecules","authors":"Carolina Muñoz-Camargo, Juan C. Cruz","doi":"10.1038/s41429-024-00744-0","DOIUrl":"10.1038/s41429-024-00744-0","url":null,"abstract":"The emergence of bacterial resistance to antibiotics poses a global health threat, necessitating innovative solutions. The contemporary challenge lies in bacterial resistance, impacting morbidity, mortality, and global economies. Antimicrobial peptides (AMPs) offer a promising avenue for addressing antibiotic resistance. The Antimicrobial Peptide Database catalogs 3569 peptides from various organisms, representing a rich resource for drug development. Histones, traditionally recognized for their role in nucleosome structures, have gained attention for their extracellular functions, including antimicrobial and immunomodulatory properties. This review aims to thoroughly investigate antimicrobial peptides derived from histones in various organisms, elucidating their mechanisms. In addition, it gives us clues about how extracellular histones might be used in drug delivery systems to fight bacterial infections. This comprehensive analysis emphasizes the importance of histone-derived peptides in developing innovative therapeutic strategies for evolving bacterial challenges.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 9","pages":"553-568"},"PeriodicalIF":2.1,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41429-024-00744-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141319047","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}

引用次数: 0

Cell morphology as biomarker of carbapenem exposure 细胞形态作为接触碳青霉烯类的生物标志物。

IF 2.1 4区医学

Journal of Antibiotics Pub Date : 2024-06-12 DOI: 10.1038/s41429-024-00749-9

Oznur Caliskan-Aydogan, Chloe Zaborney Kline, Evangelyn C. Alocilja

{"title":"Cell morphology as biomarker of carbapenem exposure","authors":"Oznur Caliskan-Aydogan, Chloe Zaborney Kline, Evangelyn C. Alocilja","doi":"10.1038/s41429-024-00749-9","DOIUrl":"10.1038/s41429-024-00749-9","url":null,"abstract":"Characterizing the physiological response of bacterial cells to antibiotics is crucial for designing diagnostic techniques, treatment choices, and drug development. While bacterial cells at sublethal doses of antibiotics are commonly characterized, the impact of exposure to high concentrations of antibiotics on bacteria after long-term serial exposure and their effect on withdrawal need attention for further characterization. This study investigated the effect of increasing imipenem concentrations on carbapenem-susceptible (S) and carbapenem-resistant (R) E. coli on their growth adaptation and cell surface structure. We exposed the bacterial population to increasing imipenem concentrations through 30 exposure cycles. Cell morphology was observed using a 3D laser scanning confocal microscope (LSCM) and transmission electron microscope (TEM). Results showed that the exposure resulted in significant morphological changes in E. coli (S) cells, while minor changes were seen in E. coli (R) cells. The rod-shaped E. coli (S) gradually transformed into round shapes. Further, the exposed E. coli (S) cells’ surface area-to-volume ratio (SA/V) was also significantly different from the control, which is non-exposed E. coli (S). Then, the exposed E. coli (S) cells were re-grown in antibiotic-free environment for 100 growth cycles to determine if the changes in cells were reversible. The results showed that their cell morphology remained round, showing that the cell morphology was not reversible. The morphological response of these cells to imipenem can assist in understanding the resistance mechanism in the context of diagnostics and antibacterial therapies.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 9","pages":"600-611"},"PeriodicalIF":2.1,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41429-024-00749-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141312287","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}

引用次数: 0

Structure revision of tricholomenyn B, an antimitotic geranylcyclohexenone rediscovered as a bitter and antibacterial substance, from a basidiomycete Tricholoma japonicum (Shiro-shimeji) 重新发现的一种苦味和抗菌物质--日本毛孢子菌（Shiro-shimeji）中的抗炎药香叶环己烯酮 tricholomenyn B 的结构修订。

IF 2.1 4区医学

Journal of Antibiotics Pub Date : 2024-05-31 DOI: 10.1038/s41429-024-00746-y

Md. Julkar Nime, Yuna Oguri, Naoya Oku, Yasuhiro Igarashi

引用次数: 0

Cytotoxic glutarimide-containing polyketides isolated from Streptomyces sp. JCM 4793 从链霉菌 JCM 4793 中分离出的含细胞毒性戊二酰亚胺的多酮类化合物。

IF 2.1 4区医学

Journal of Antibiotics Pub Date : 2024-05-30 DOI: 10.1038/s41429-024-00743-1

Lin-Fang Tang, Wu-Lai Jihuo, Pei-Dong Shi, Cui-Xuan Mei, Zi-Kang Zhao, Yuan Chen, Ying-Tong Di, Xiao‑Jiang Hao, Mingming Cao, Yi Zhao, Yan-Yun Che

引用次数: 0

Biosynthesis of macrolactam antibiotics with β-amino acid polyketide starter units 大内酰胺类抗生素与β-氨基酸聚酮起始单元的生物合成。

IF 2.1 4区医学

Journal of Antibiotics Pub Date : 2024-05-30 DOI: 10.1038/s41429-024-00742-2

Fumitaka Kudo

引用次数: 0

Isolation, structural determination, and antiviral activities of a novel alanine-conjugated polyketide from Talaromyces sp. 从塔拉酵母菌（Talaromyces sp.

IF 2.1 4区医学

Journal of Antibiotics Pub Date : 2024-05-30 DOI: 10.1038/s41429-024-00740-4

Nozomi Mosu, Mitsuki Yasukochi, Shogo Nakajima, Kou Nakamura, Masaya Ogata, Keita Iguchi, Kazuki Kanno, Tomohiro Ishikawa, Kazutoshi Sugita, Hironobu Murakami, Kouji Kuramochi, Tatsuo Saito, Shiro Takeda, Koichi Watashi, Kan Fujino, Shinji Kamisuki

引用次数: 0

Streptomyces chengbuensis sp. nov., isolated from the rhizosphere soil of Cathaya argyrophylla 从 Cathaya argyrophylla 根瘤土壤中分离出的 Streptomyces chengbuensis sp.

IF 2.1 4区医学

Journal of Antibiotics Pub Date : 2024-05-29 DOI: 10.1038/s41429-024-00745-z

Yaxi Zheng, Ping Mo, Chenxi Li, Zhibo Zhou, Zhifang Zhang, Haixian Zhu, Kerui Huang, Yun Wang

{"title":"Streptomyces chengbuensis sp. nov., isolated from the rhizosphere soil of Cathaya argyrophylla","authors":"Yaxi Zheng, Ping Mo, Chenxi Li, Zhibo Zhou, Zhifang Zhang, Haixian Zhu, Kerui Huang, Yun Wang","doi":"10.1038/s41429-024-00745-z","DOIUrl":"10.1038/s41429-024-00745-z","url":null,"abstract":"Strain HUAS CB01T was a novel actinobacterium which was isolated from the rhizosphere soil of Cathaya argyrophylla, Chengbu Miao Autonomous County of Hunan Province, China. The strain formed well-growing substrate mycelium, diffusible pigments, and aerial mycelium, and differentiated into spiral-type spore chains composed of smooth-surface rod-shaped spores. Phylogenetic analysis on account of 16 S rRNA gene sequence demonstrated the strain HUAS CB01T was a member of the genus Streptomyces and had a close relationship with Streptomyces wuyuanensis CGMCC 4.7042 T (100%) and Streptomyces marianii ICN19T (99.86%). Genome-based comparisons indicated that strain HUAS CB01T could be distinctly different from its closest species, Streptomyces wuyuanensis CGMCC 4.7042 T, Streptomyces marianii ICN19T, with ANIm and dDDH results of 92.78% and 45.90%, 92.22% and 43.30%, respectively, far less than 96.7 and 70% cut-off points recommended for delineating species. The main cellular fatty acids concluded anteiso-C15:0, iso-C14:0, iso-C16:0, C16:0 and C16:1 2OH. The menaquinones were MK-9(H4), MK-9(H6) and MK-9(H8) and the whole-cell sugars consisted of ribose and mannose. The polar lipids included phosphatidyl ethanolamine, diphosphatidylglycerol, phosphatidylglycerol, mannosides and unidentified phospholipids. According to these genotypic and phenotypic characteristics, strain HUAS CB01T can be distinguished and representative to be a novel species of the genus Streptomyces, for which the name Streptomyces chengbuensis is proposed. The type strain is HUAS CB01T ( = MCCC 1K08666T = JCM 36277 T).","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 9","pages":"569-576"},"PeriodicalIF":2.1,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141171551","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