Author: Jin, Faxiang ; Yu, Zhongqiang ; Wang, Yanan ; Yu, Yefu ; Wang, Huiyu ; Gao, Junshun ; Yang, Guier ; Li, Lanqing ; Li, Xiangcheng ; Xu, Wenfang

BackgroundActinomadura geliboluensis was first isolated in 2012 in Gelibolu, Canakkale, Turkey, and has not been reported to be isolated from humans until now. We have isolated it from the bronchoalveolar lavage fluid (BLF) of a patient with pneumonia and found its drug resistance. It is the first time that Actinomadura geliboluensis has been isolated from humans since its discovery and naming. This case may provide new ideas and methods for the clinical diagnosis and treatment of pulmonary actinomycosis.Case DescriptionThe patient was a 75-year-old male who was hospitalized in a township hospital and failed to improve after penicillin treatment. After admission to our hospital, the patient was treated with piperacillin/tazobactam according to clinical guidelines for 14 days. Actinomadura geliboluensis was isolated from the patient's BLF and was identified by 16S rRNA sequencing. This report shows the biological characteristics and in vitro drug susceptibility testing, as well as the genomics analysis based on next-generation sequencing (NGS). The results demonstrated that Actinomadura geliboluensis was easy to be mistakenly identified as Actinomyces dental caries by using the Merieux ANC identification card. Based on the MIC test, Actinomadura geliboluensis was susceptible to tetracyclines, quinolones and sulfonamides, but resistant to carbapenems, penicillins and cephalosporins. The K-B test results showed Actinomadura geliboluensis was highly sensitive to piperacillin/tazobactam. Genomic analysis based on NGS showed that the Actinomadura geliboluensis belongs to Planobispora rosea EF-Tu mutants conferring resistance to inhibitor GE2270A, AAC(3)-VIIa, vanRO, chrB, and mexY.ConclusionActinomycetes is generally sensitive to Penicillin but Actinomadura geliboluensis is not. In vitro drug susceptibility test is needed to support individualized drug use to avoid delay in the disease.

29 Jun 2021·mSystemsQ2 · BIOLOGY

Multi-omics Study of Planobispora rosea, Producer of the Thiopeptide Antibiotic GE2270A

Q2 · BIOLOGY

ArticleOA

Author: Donadio, Stefano ; Pérez-Redondo, Rosario ; Genilloud, Olga ; Sosio, Margherita ; Pérez-Bonilla, Mercedes ; Rodríguez-García, Antonio ; Breitling, Rainer ; Thomas, Gavin H. ; Del Carratore, Francesco ; Gyulev, Ivan S. ; Schmidt, Kamila ; Tsigkinopoulou, Areti ; Macdonald, Sandy J. ; Iorio, Marianna ; Takano, Eriko

Planobispora roseais a genetically intractable bacterium used for the production of GE2270A on an industrial scale. GE2270A is a potent thiopeptide antibiotic currently used as a precursor for the synthesis of two compounds under clinical studies for the treatment ofClostridium difficileinfection and acne.

01 Jun 2018·ASSAY and Drug Development Technologies

Engineered EF-Tu and tRNA-Based FRET Screening Assay to Find Inhibitors of Protein Synthesis in Bacteria

Article

Author: Bhatt, Rachana ; Chudaev, Maxim ; Goldman, Emanuel ; Mandecki, Wlodek

Antibiotic-resistant infections that do not respond to available drugs are becoming more common. Methicillin-resistant Staphylococcus aureus, carbapenem-resistant enterobacteria ("superbugs"), and many others pose a continuous threat to public health. To provide tools to combat such deadly infections, we present in this study a homogeneous assay focused on an insufficiently addressed molecular interaction linked to ribosomal translation. We show that a fluorescence resonance energy transfer (FRET) based screening assay can identify antibiotic molecules that inhibit ternary complex (EF-Tu:tRNA:GTP complex) formation, and therefore, protein synthesis in bacteria. Specifically engineered Escherichia coli EF-Tu and tRNA^Phe are used to prepare two key components of this assay: (1) Cy5-EF-Tu:GTP and (2) Cy3-Phe-tRNA^Phe. When mixed and Cy3 is excited at 532 nm, increased Cy5 fluorescence intensity is observed at 665 nm due to ternary complex formation and FRET. If the same assay is carried out in presence of an inhibitor, such as GE2270A (a known inhibitor of the EF-Tu-tRNA interaction), fluorescence intensity is significantly diminished. To establish proof of principle and to show the adaptability of this assay to high throughput screening (HTS), we analyzed the effect of different classes of antibiotics, including beta-lactams, quinolone compounds, and protein synthesis inhibitors, on fluorescence. The assay was done in a 96-well microplate. We observed inhibition by GE2270A, and no effect of nineteen other tested antibiotics, confirming the ability of this FRET assay to serve as a screen for potential inhibitor molecules of ternary complex formation from libraries of compounds.

100 Deals associated with GE-2270 factor A

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