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.
{"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}
Pub Date : 2024-06-13DOI: 10.1038/s41429-024-00744-0
Carolina Muñoz-Camargo, Juan C. Cruz
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.
{"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}
Pub Date : 2024-06-12DOI: 10.1038/s41429-024-00749-9
Oznur Caliskan-Aydogan, Chloe Zaborney Kline, Evangelyn C. Alocilja
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.
{"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}
Tricholomenyn B, an antimitotic geranylcyclohexenone originally discovered from a basidiomycete Tricholoma acerbum, was isolated as a bitter and antibacterial constituent from fruiting bodies of T. japonicum. Careful comparison of NMR, MS, and other physicochemical properties of the isolated substance with the literature values revised a previously proposed macrolide structure 1 to a macrodiolide 2. Compound 2 was perceived bitter at a minimum dose of 37.5 μg, showed weak antimicrobial activity against Kocuria rhizophila and Staphylococcus aureus, and was marginally cytotoxic (IC50 2.6 µM) against P388 murine leukemia cells.
{"title":"Structure revision of tricholomenyn B, an antimitotic geranylcyclohexenone rediscovered as a bitter and antibacterial substance, from a basidiomycete Tricholoma japonicum (Shiro-shimeji)","authors":"Md. Julkar Nime, Yuna Oguri, Naoya Oku, Yasuhiro Igarashi","doi":"10.1038/s41429-024-00746-y","DOIUrl":"10.1038/s41429-024-00746-y","url":null,"abstract":"Tricholomenyn B, an antimitotic geranylcyclohexenone originally discovered from a basidiomycete Tricholoma acerbum, was isolated as a bitter and antibacterial constituent from fruiting bodies of T. japonicum. Careful comparison of NMR, MS, and other physicochemical properties of the isolated substance with the literature values revised a previously proposed macrolide structure 1 to a macrodiolide 2. Compound 2 was perceived bitter at a minimum dose of 37.5 μg, showed weak antimicrobial activity against Kocuria rhizophila and Staphylococcus aureus, and was marginally cytotoxic (IC50 2.6 µM) against P388 murine leukemia cells.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 9","pages":"634-637"},"PeriodicalIF":2.1,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141185035","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}
Glutarimide-containing polyketides usually exhibit anti-fungi activity, which was well exampled by cycloheximide. In our work, three new polyketide structures, 12-amidestreptimidone (1), 12-carboxylstreptimidone (2) and 3-(5S,8R)-(2-amino-2-oxoethyl-2’-methoxy-2’-oxoethyl)-8,10-dimethyl-7-oxododeca-5-hydroxy-9E,11-diolefin (3) were isolated from Streptomyces sp. JCM 4793. 3 without the glutarimide moiety is not active against fungi as expected, while 1 bearing the amide moiety is much more active than its carboxylic form 2. Here we report the isolation, structural elucidation, antifungal activity, and proposed biosynthesis pathway of 1–3.
{"title":"Cytotoxic glutarimide-containing polyketides isolated from Streptomyces sp. JCM 4793","authors":"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","doi":"10.1038/s41429-024-00743-1","DOIUrl":"10.1038/s41429-024-00743-1","url":null,"abstract":"Glutarimide-containing polyketides usually exhibit anti-fungi activity, which was well exampled by cycloheximide. In our work, three new polyketide structures, 12-amidestreptimidone (1), 12-carboxylstreptimidone (2) and 3-(5S,8R)-(2-amino-2-oxoethyl-2’-methoxy-2’-oxoethyl)-8,10-dimethyl-7-oxododeca-5-hydroxy-9E,11-diolefin (3) were isolated from Streptomyces sp. JCM 4793. 3 without the glutarimide moiety is not active against fungi as expected, while 1 bearing the amide moiety is much more active than its carboxylic form 2. Here we report the isolation, structural elucidation, antifungal activity, and proposed biosynthesis pathway of 1–3.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 9","pages":"627-633"},"PeriodicalIF":2.1,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141181529","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 : 2024-05-30DOI: 10.1038/s41429-024-00742-2
Fumitaka Kudo
Macrolactam antibiotics incorporating β-amino acid polyketide starter units, isolated primarily from Actinomycetes species, show significant biological activities. This review provides a detailed analysis into the biosynthetic studies of vicenistatin, a macrolactam antibiotic with a 3-aminoisobutyrate starter unit, as well as biosynthetic research on related macrolactam compounds. Firstly, the elucidation of a common mechanism for the incorporation of β-amino acid starter units into the polyketide synthase (PKS) is described. Secondly, the unique biosynthetic mechanisms of the β-amino acids that are used to supply the main macrolactam biosynthetic pathways with starter units are discussed. Thirdly, some distinctive post-PKS modification mechanisms that complete macrolactam antibiotic biosynthesis are summarized. Finally, future directions for creating new macrolactam compounds through engineered biosynthesis pathways are described.
{"title":"Biosynthesis of macrolactam antibiotics with β-amino acid polyketide starter units","authors":"Fumitaka Kudo","doi":"10.1038/s41429-024-00742-2","DOIUrl":"10.1038/s41429-024-00742-2","url":null,"abstract":"Macrolactam antibiotics incorporating β-amino acid polyketide starter units, isolated primarily from Actinomycetes species, show significant biological activities. This review provides a detailed analysis into the biosynthetic studies of vicenistatin, a macrolactam antibiotic with a 3-aminoisobutyrate starter unit, as well as biosynthetic research on related macrolactam compounds. Firstly, the elucidation of a common mechanism for the incorporation of β-amino acid starter units into the polyketide synthase (PKS) is described. Secondly, the unique biosynthetic mechanisms of the β-amino acids that are used to supply the main macrolactam biosynthetic pathways with starter units are discussed. Thirdly, some distinctive post-PKS modification mechanisms that complete macrolactam antibiotic biosynthesis are summarized. Finally, future directions for creating new macrolactam compounds through engineered biosynthesis pathways are described.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 8","pages":"486-498"},"PeriodicalIF":2.1,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11284099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141181527","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}
Antiviral agents are highly sought after. In this study, a novel alkylated decalin-type polyketide, alaspelunin, was isolated from the culture broth of the fungus Talaromyces speluncarum FMR 16671, and its structure was determined using spectroscopic analyses (1D/2D NMR and MS). The compound was condensed with alanine, and its absolute configuration was determined using Marfey’s method. Furthermore, the antiviral activity of alaspelunin against various viruses was evaluated, and it was found to be effective against both severe acute respiratory syndrome coronavirus 2 and pseudorabies (Aujeszky’s disease) virus, a pathogen affecting pigs. Our results suggest that this compound is a potential broad-spectrum antiviral agent.
{"title":"Isolation, structural determination, and antiviral activities of a novel alanine-conjugated polyketide from Talaromyces sp.","authors":"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","doi":"10.1038/s41429-024-00740-4","DOIUrl":"10.1038/s41429-024-00740-4","url":null,"abstract":"Antiviral agents are highly sought after. In this study, a novel alkylated decalin-type polyketide, alaspelunin, was isolated from the culture broth of the fungus Talaromyces speluncarum FMR 16671, and its structure was determined using spectroscopic analyses (1D/2D NMR and MS). The compound was condensed with alanine, and its absolute configuration was determined using Marfey’s method. Furthermore, the antiviral activity of alaspelunin against various viruses was evaluated, and it was found to be effective against both severe acute respiratory syndrome coronavirus 2 and pseudorabies (Aujeszky’s disease) virus, a pathogen affecting pigs. Our results suggest that this compound is a potential broad-spectrum antiviral agent.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 8","pages":"499-505"},"PeriodicalIF":2.1,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41429-024-00740-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141181534","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}
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).
{"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}
Pub Date : 2024-05-24DOI: 10.1038/s41429-024-00741-3
Shan Lu, Lingling Ren, Di Mao, Hideaki Kakeya
Saccharothriolide L (1), a derivative of saccharothriolides (STLs) produced by the rare actinomycete Saccharotrix sp. A1506, was synthesized through the precursor-directed in situ synthesis (PDSS) method. The structure of 1 was determined by 1D and 2D NMR and HR-ESI-MS data analyses. A comparison of the rate of the retro-aza-Michael reaction between saccharothriolide L (1) and saccharothriolide B (2) indicated that the 2-amino-4-methylphenol group in 1 might be an effective masking tool for highly reactive, bioactive α, β-unsaturated carbonyl compounds.
{"title":"Mechanistic study of the retro-aza-Michael reaction in saccharothriolide L: identification of 2-amino-4-methylphenol as an effective protecting tool for the Michael acceptor","authors":"Shan Lu, Lingling Ren, Di Mao, Hideaki Kakeya","doi":"10.1038/s41429-024-00741-3","DOIUrl":"10.1038/s41429-024-00741-3","url":null,"abstract":"Saccharothriolide L (1), a derivative of saccharothriolides (STLs) produced by the rare actinomycete Saccharotrix sp. A1506, was synthesized through the precursor-directed in situ synthesis (PDSS) method. The structure of 1 was determined by 1D and 2D NMR and HR-ESI-MS data analyses. A comparison of the rate of the retro-aza-Michael reaction between saccharothriolide L (1) and saccharothriolide B (2) indicated that the 2-amino-4-methylphenol group in 1 might be an effective masking tool for highly reactive, bioactive α, β-unsaturated carbonyl compounds.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 8","pages":"544-547"},"PeriodicalIF":2.1,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141094591","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 : 2024-05-21DOI: 10.1038/s41429-024-00739-x
Hiroshi Hamamoto
The development of novel antimicrobial agents is required to solve the problem of antimicrobial resistance. We established a quantitative method for evaluating the therapeutic efficacy of antimicrobial agents in a silkworm bacterial infection model. Pharmacokinetic factors are present in the silkworm as well as in mice, and evaluating the therapeutic efficacy of antimicrobial agents is possible in a silkworm infection model, comparable to that in a mammalian model. This silkworm model was used to screen for novel antimicrobial agents with therapeutic efficacy as an indicator. As a result, a new antibiotic, lysocin E, was discovered. Lysocin E has a completely different mechanism of action from existing antimicrobial agents, and its potent bactericidal activity leads to remarkable therapeutic efficacy in a mouse model. In this review, I describe the features of the silkworm model that have contributed to the discovery of lysocin E and its mechanisms of action.
要解决抗菌剂耐药性问题，就必须开发新型抗菌剂。我们建立了一种在家蚕细菌感染模型中评估抗菌剂疗效的定量方法。蚕和小鼠一样存在药代动力学因素，因此在蚕感染模型中评估抗菌剂的疗效与在哺乳动物模型中评估疗效相当。这种家蚕模型被用来筛选以疗效为指标的新型抗菌剂。结果发现了一种新的抗生素--溶菌酶 E。溶菌酶 E 的作用机制与现有的抗菌剂完全不同，其强大的杀菌活性使其在小鼠模型中具有显著的疗效。在这篇综述中，我将介绍有助于发现溶菌酶 E 及其作用机制的家蚕模型的特点。
{"title":"Silkworm model of bacterial infection facilitates the identification of lysocin E, a potent, ultra-rapid bactericidal antibiotic","authors":"Hiroshi Hamamoto","doi":"10.1038/s41429-024-00739-x","DOIUrl":"10.1038/s41429-024-00739-x","url":null,"abstract":"The development of novel antimicrobial agents is required to solve the problem of antimicrobial resistance. We established a quantitative method for evaluating the therapeutic efficacy of antimicrobial agents in a silkworm bacterial infection model. Pharmacokinetic factors are present in the silkworm as well as in mice, and evaluating the therapeutic efficacy of antimicrobial agents is possible in a silkworm infection model, comparable to that in a mammalian model. This silkworm model was used to screen for novel antimicrobial agents with therapeutic efficacy as an indicator. As a result, a new antibiotic, lysocin E, was discovered. Lysocin E has a completely different mechanism of action from existing antimicrobial agents, and its potent bactericidal activity leads to remarkable therapeutic efficacy in a mouse model. In this review, I describe the features of the silkworm model that have contributed to the discovery of lysocin E and its mechanisms of action.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"77 8","pages":"477-485"},"PeriodicalIF":2.1,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41429-024-00739-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141074543","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}
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