Journal of Antibiotics最新文献_第2页

Aztreonam-avibactam: a new combination with activity against multidrug-resistant Klebsiella pneumoniae complex. Aztreonam-avibactam：一种具有抗多药耐药肺炎克雷伯菌复合物活性的新组合。

IF 2.1 4区医学

Journal of Antibiotics Pub Date : 2025-01-07 DOI: 10.1038/s41429-024-00803-6

Alicja Sękowska

{"title":"Aztreonam-avibactam: a new combination with activity against multidrug-resistant Klebsiella pneumoniae complex.","authors":"Alicja Sękowska","doi":"10.1038/s41429-024-00803-6","DOIUrl":"https://doi.org/10.1038/s41429-024-00803-6","url":null,"abstract":"Klebsiella pneumoniae complex (KPc) is a group of opportunistic pathogens that pose a serious threat to public health. Multidrug resistance is increasing, and limiting therapeutic options. Aztreonam-avibactam (AZA) is a combination of an established β-lactam with a new β-lactamase inhibitor. The aim of this study was to assess the susceptibility of multidrug-resistant KPc strains to AZA. The study included 52 ESβL-positive strains and 152 carbapenemase-positive KPc strains. The susceptibility to AZA was tested using the gradient strip method. AZA showed high activity against KPc, with MICs ranging from 0.032 to 0.75 μg ml-1 for ESβL-positive strains and from 0.016 to 2 μg ml-1 for carbapenemase-positive strains. The lowest MIC50 of AZA was obtained for VIM- and ESβL-positive strains at 0.094 μg ml-1, and MIC90 for ESβL-positive strains was 0.125 μg ml-1. AZA demonstrated excellent in vitro activity against the analysed strains, suggesting that this antibiotic may be an effective therapeutic option for treating infections caused by multidrug-resistant KPc strains.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142959092","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

Winners of the 2023 JA Ōmura Awards for excellence 2023年JA Ōmura优秀奖得主

IF 2.1 4区医学

Journal of Antibiotics Pub Date : 2025-01-06 DOI: 10.1038/s41429-024-00784-6

Richard E. Lee, Minoru Yoshida

引用次数: 0

Activity of cefiderocol in combination with tetracycline analogues against carbapenem-resistant Acinetobacter baumannii. 头孢地罗与四环素类似物联合对耐碳青霉烯鲍曼不动杆菌的活性研究。

IF 2.1 4区医学

Journal of Antibiotics Pub Date : 2024-12-23 DOI: 10.1038/s41429-024-00801-8

Yuhan Yin, Na Xu, Xinjie Wang

{"title":"Activity of cefiderocol in combination with tetracycline analogues against carbapenem-resistant Acinetobacter baumannii.","authors":"Yuhan Yin, Na Xu, Xinjie Wang","doi":"10.1038/s41429-024-00801-8","DOIUrl":"https://doi.org/10.1038/s41429-024-00801-8","url":null,"abstract":"Therapeutic options for carbapenem-resistant Acinetobacter baumannii (CA-AB) are quite limited. Cefiderocol, a novel siderophore cephalosporin, has shown potent in vitro activity against CR-AB, and new tetracycline analogues such as eravacycline and omadacycline have been available in recent years. However, the synergism of cefiderocol with tetracycline analogues against CR-AB has not been well investigated. In this study, we evaluated the in vitro synergistic activity of cefiderocol in combination with tetracycline analogues (minocycline, tigecycline, eravacycline and omadacycline) against 48 clinical isolates of CR-AB by checkerboard methods and time-kill assays. Then we further verified the in vitro results with neutropenic murine thigh-infection models. Among 48 tested isolates tested with checkerboard methods, 35.4%, 33.3%, 50.0% and 37.5% showed synergistic interactions (FICI ≤ 0.5) in cefiderocol-minocycline combination, cefiderocol-tigecycline combination, cefiderocol-eravacycline combination and cefiderocol-omadacycline combination, respectively. None of the combinations exhibited any antagonistic interactions. In the time-kill assays, cefiderocol combined with tetracycline analogues showed synergistic effects in most isolates. Animal models found that combination therapy could reduce cell counts by nearly 2 log10 CFU/thigh compared with the monotherapy in the AB-2 isolate who was susceptible to minocycline (MIC = 4 mg/l). But for the AB-26 who was resistant to minocycline, the decrease of bacterial cell counts was less than 1 log10 CFU/thigh compared with cefiderocol monotherapy in the cefiderocol-minocycline, cefiderocol-tigecycline and cefiderocol-omadacycline therapies; while the cefiderocol-eravacycline combination could still reduce the bacterial cell counts nearly 2 log10 CFU/thigh compared with the monotherapy. In summary, the cefiderocol-eravacycline combination seems to be a promising therapeutic strategy for treating CR-AB infections.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883563","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

Therapeutic potential of isoallolithocholic acid in methicillin-resistant Staphylococcus Aureus peritoneal infection. 异丙胆酸治疗耐甲氧西林金黄色葡萄球菌腹膜感染的潜力。

IF 2.1 4区医学

Journal of Antibiotics Pub Date : 2024-12-17 DOI: 10.1038/s41429-024-00800-9

Ying Lu, Jun Du, Shicheng Peng, Ying Wang, Yongtao Xiao

{"title":"Therapeutic potential of isoallolithocholic acid in methicillin-resistant Staphylococcus Aureus peritoneal infection.","authors":"Ying Lu, Jun Du, Shicheng Peng, Ying Wang, Yongtao Xiao","doi":"10.1038/s41429-024-00800-9","DOIUrl":"https://doi.org/10.1038/s41429-024-00800-9","url":null,"abstract":"A significant increase in multidrug-resistant Methicillin-resistant Staphylococcus aureus (MRSA) infections has made it crucial to explore new antimicrobial drugs and strategies. Emerging evidence suggests that the bile acid metabolite isoallolithocholic acid (isoallo-LCA) may contribute to reducing the risk of infection among centenarians. However, its precise role remains somewhat ambiguous and necessitates further investigation. This study aims to investigate the roles of isoallo-LCA in MRSA-associated peritoneal infection. The effects of isoallo-LCA on peritoneal infection are examined in a MRSA-induced peritoneal infected model. Antibacterial activity, biofilm formation assay, and bacterial membrane permeability experiments are conducted to explore the mechanisms involved. Our findings demonstrate that isoallo-LCA effectively suppresses the replication of MRSA with minimal adverse effects on mammalian cells. Furthermore, isoallo-LCA significantly inhibits the formation of bacterial biofilms and eradicates existing bacterial biofilms of MRSA. Administration of isoallo-LCA reduces MRSA colonization in peritoneal organs and alleviates peritonitis-related inflammation and damage in a MRSA-infected peritonitis mice. Mechanistically, isoallo-LCA exhibits potent bactericidal activity against MRSA by disrupting the integrity and permeability of bacterial cells. In addition, isoallo-LCA also enhances the macrophage phagocytosis. In conclusion, our results suggest that isoallo-LCA could be an effective treatment for infections caused by MRSA.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848249","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

Novobiocin primarily targets ParE in Neisseria gonorrhoeae. 新生物素主要靶向淋病奈瑟菌的ParE。

IF 2.1 4区医学

Journal of Antibiotics Pub Date : 2024-12-16 DOI: 10.1038/s41429-024-00797-1

Yoshimasa Ishizaki, Chigusa Hayashi, Kazuaki Matoba, Masayuki Igarashi

引用次数: 0

Structure-function analysis of 2-sulfamoylacetic acid synthase in altemicidin biosynthesis. 阿霉素生物合成中2-磺胺酰乙酸合酶的结构-功能分析。

IF 2.1 4区医学

Journal of Antibiotics Pub Date : 2024-12-13 DOI: 10.1038/s41429-024-00798-0

Takahiro Mori, Kosuke Sakurada, Takayoshi Awakawa, Haibin He, Richiro Ushimaru, Ikuro Abe

{"title":"Structure-function analysis of 2-sulfamoylacetic acid synthase in altemicidin biosynthesis.","authors":"Takahiro Mori, Kosuke Sakurada, Takayoshi Awakawa, Haibin He, Richiro Ushimaru, Ikuro Abe","doi":"10.1038/s41429-024-00798-0","DOIUrl":"https://doi.org/10.1038/s41429-024-00798-0","url":null,"abstract":"Altemicidin and its analogs are valuable sulfonamide antibiotics with valuable antitumor and antibacterial activities. Structures of altemicidin and congeners feature an unusual sulfonamide side chain. In the biosynthesis of altemicidin, the aldehyde dehydrogenase SbzJ catalyzes the conversion of 2-sulfamoylacetic aldehyde into 2-sulfamoylacetic acid, a key step in producing the sulfonamide side chain. Here, we conducted the biochemical characterization and structure-function analysis of SbzJ. In vitro assays revealed that SbzJ exhibits substrate promiscuity, accepting various aldehyde substrates and cofactors. The crystal structure of SbzJ in complex with NAD+, along with subsequent mutagenesis studies, provided insights into how SbzJ recognizes the sulfonamide group of the substrate. Notably, His431 and Glu240 were identified as key residues serving as catalytic bases to activate the catalytic Cys273 and a water molecule. These findings provide structural and mechanistic understanding of SbzJ, offering potential for enzyme engineering to generate novel bioactive compounds.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822920","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

Inhibitors of acetohydroxyacid synthase as promising agents against non-tuberculous mycobacterial diseases. 乙酰羟基酸合酶抑制剂作为抗非结核分枝杆菌疾病的有前途的药物。

IF 2.1 4区医学

Journal of Antibiotics Pub Date : 2024-12-13 DOI: 10.1038/s41429-024-00799-z

Tam Doan Nguyen, Ji-Ae Choi, Hee-Jong Lim, Chong Hak Chae, Junghwan Lee, Sang-Hun Son, Jaewhan Kim, Doyi Son, Hwa-Jung Kim, Chang-Hwa Song

{"title":"Inhibitors of acetohydroxyacid synthase as promising agents against non-tuberculous mycobacterial diseases.","authors":"Tam Doan Nguyen, Ji-Ae Choi, Hee-Jong Lim, Chong Hak Chae, Junghwan Lee, Sang-Hun Son, Jaewhan Kim, Doyi Son, Hwa-Jung Kim, Chang-Hwa Song","doi":"10.1038/s41429-024-00799-z","DOIUrl":"https://doi.org/10.1038/s41429-024-00799-z","url":null,"abstract":"Acetohydroxyacid synthase (AHAS), exclusively present in microorganisms and plants, is a promising target for several herbicides due to its catalytic role in the branched-chain amino acid biosynthetic pathway. Previous studies have shown that K13787, a pyrazolopyrimidine sulfonamide AHAS inhibitor, was moderately effective against pulmonary infection caused by M. tuberculosis and nontuberculous mycobacteria (NTM). In this study, we synthesized various structural derivatives of K13787 based on the molecular docking studies and assessed their MICs against mycobacteria species. Among the synthetic compounds screened, K13787, along with KNT2077 and KNT2099, exhibited inhibitory efficacy against M. avium and M. abscessus, including CLR-resistant NTM species. Notably, these compounds displayed a synergistic effect (FIC ≤ 0.5) when combined with CLR against M. avium and M. abscessus. Our findings suggest that these newly identified AHAS-targeted compounds hold promise as lead candidates for novel antimycobacterial agents against NTM infections. Considering the structure-activity relationship, K13787, KNT2077, and KTN2099 emerge as potential treatments for NTM species.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822919","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

Differential gene expression analysis shows that cephalosporin resistance is intrinsic to Clostridioides difficile strain 630 差异基因表达分析表明，艰难梭菌菌株630对头孢菌素具有内在抗性。

IF 2.1 4区医学

Journal of Antibiotics Pub Date : 2024-12-13 DOI: 10.1038/s41429-024-00795-3

Lara A. Turello, Amber Consul, Christopher Yip, Shirley Shen, Cale Seymour, Corey Geurink, Israel Alvarado, Ernesto Abel-Santos

{"title":"Differential gene expression analysis shows that cephalosporin resistance is intrinsic to Clostridioides difficile strain 630","authors":"Lara A. Turello, Amber Consul, Christopher Yip, Shirley Shen, Cale Seymour, Corey Geurink, Israel Alvarado, Ernesto Abel-Santos","doi":"10.1038/s41429-024-00795-3","DOIUrl":"10.1038/s41429-024-00795-3","url":null,"abstract":"Clostridioides difficile infection (CDI) is the most common nosocomial infection in the US. CDI has become a growing concern due to C. difficile’s resistance to several antibiotics, including cephalosporins. Furthermore, patients administered cephalosporins are at higher risk of contracting CDI. Cephalosporins are β-lactam antibiotics, which prevent bacterial cell wall synthesis by inhibiting penicillin-binding proteins (PBPs). β-lactam-resistant bacteria evade these antibiotics by producing β-lactamases or by harboring low-affinity PBPs. A genomic analysis of C. difficile strain 630 identified 31 putative β-lactam resistance genes. Upon cefoxitin exposure, few C. difficile strain 630 putative antibiotic-resistant genes were overexpressed. Most notably, the β-lactamase blaCDD gene was upregulated approximately 600-fold, as previously reported. Deletion of the blaCDD locus did not change in cephalosporin susceptibility. Deletion of the second most upregulated gene, the PBP vanY, was also ineffective at decreasing cephalosporin resistance. Cefoxitin exposure of the C. difficile strain 630ΔblaCDD mutant did not increase upregulation of other putative antibiotic resistance genes compared to wildtype C. difficile strain 630. Transcriptomic analyses of wildtype C. difficile strain 630 exposed to cephradine, cefoxitin, ceftazidime, or cefepime revealed the shared upregulation of a putative heterodimeric ABC transporter encoded by loci CD630_04590 (ABC transporter ATP-binding protein) and CD630_04600 (ABC transporter permease). These genes are genomically located directly downstream of blaCDD (CD630_04580). The deletion mutant CD630_04600 remained resistant to a number of antibiotics. Thus, even though blaCDD, CD630_04590, and CD630_04600 are all upregulated when exposed to cephalosporins, they do not seem to be involved in antibiotic resistance in C. difficile strain 630.","PeriodicalId":54884,"journal":{"name":"Journal of Antibiotics","volume":"78 2","pages":"113-125"},"PeriodicalIF":2.1,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822917","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

Multiplexed activity metabolomics for isolation of filipin macrolides from a hypogean actinomycete 多重活性代谢组学从一种次源放线菌中分离大环内酯类。

IF 2.1 4区医学

Journal of Antibiotics Pub Date : 2024-12-06 DOI: 10.1038/s41429-024-00792-6

Jordan T. Froese, Joseph A. Balsamo, Benjamin J. Reisman, Sierra M. Barone, Jonathan M. Irish, Brian O. Bachmann

引用次数: 0

Correction: Xantholipin B produced by the stnR inactivation mutant Streptomyces flocculus CGMCC 4.1223 WJN-1. 更正：由stnR失活突变体小叶链霉菌CGMCC 4.1223 WJN-1产生的黄嘌呤B。

IF 2.1 4区医学

Journal of Antibiotics Pub Date : 2024-12-06 DOI: 10.1038/s41429-024-00796-2

Sifan Wu, Tingting Huang, Dan Xie, Jing Wo, Xiaozheng Wang, Zixin Deng, Shuangjun Lin

引用次数: 0