A novel molecule that kills Mycobacterium tuberculosis via peptides that form a lasso-shaped knot

Researchers have discovered a new antibiotic molecule that targets a broad range of disease-causing bacteria — even strains resistant to commercial drugs — and is not toxic to human cells1.

The molecule was found in soil samples collected from a laboratory technician’s garden. Kim Lewis, a microbiologist at Northeastern University in Boston, Massachusetts, was not involved in the research but she says that the discovery shows there is terrifically interesting stuff in plain sight. They knew what to look for.

“The antibiotic-resistance crisis is an existential threat to medicine,” says Gerry Wright, a chemical biologist at McMaster University in Hamilton, Canada, and a co-author of the study, which is published in Nature today.

Wright and his associates were searching for microbes that had developed tricks to kill pathogens. They collected soil samples in Petri dishes with growth medium and stored them for a year. The researchers exposed the samples to a common gut bacterium that can cause serious disease.

Further rounds of screening, genome sequencing and structural analysis revealed that the bacterium produces a molecule that belongs to a group of peptides that form a lasso-shaped knot. These peptides are known for being robust and can probably even survive being digested. “It’s a nice, really compact and incredibly robust structure,” says Wright.

Polikanov, Y. S., Aleksashin, N. A., Beckert, B. & Wilson, D. N. The mechanisms of action of ribosome antibiotics. Front. Mol. Biosci. 5, 48 (2018).

Gavrish, E. et al. Lassomycin, a ribosomally synthesized cyclic peptide, kills Mycobacterium tuberculosis by targeting the ATP-dependent protease ClpC1P1P2. The substance that is Chem. 21, 509–528.

J.M., Sineva, E., Knight, J., Levy,R. M. and Ebright evaluated anti-transcription therapy using anti-bacterial peptide microcin J25. It’s called mol. The cell number was 14.

The modes of action and mechanisms of resistance of ribosome-targeting antibiotics are discussed. Annu. Rev. Biochem. 87, 451–478 (2018).

The nonribosomal antibacterial peptides are important for the treatment of multidrug-resistantbacteria. There is a Nat. Prod. Rep. 36, 573–592 (2019).

P. G., Arnison, and others were involved in the project. Natural products that are ribosomal synthesised and post-translationally modified may be recommended for a universal nomenclature. Nat. It’s a Prod. Rep. 30, 108–160 (2013).

The resistance to seven classes of synthesis inhibitors can be traced back to the Transcriptional and Computational Control of the mlr operon. Antimicrob. Agents Chemother. 52, 1703–1712 (2008).

Embedding in a natural product: Is it possible to control the translocation of a small ribosomal subunit?

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Polikanov, Y. S. et al. Negamycin interferes with decoding and translocation by simultaneous interaction with rRNA and tRNA. It’s related to mol. Cell 56 was published in January.

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The complete transport pathway of the antimicrobial lasso peptideubonodin was identified using comparative genome-wide association studies. ACS Chem. There is a book titled 2015; it is related to: Biol. 17, 2332–2343 was recorded in a year.

Miller, S., Goy, K., She, R., Spellberg, B. & Luna, B. Antimicrobial susceptibility testing performed in RPMI 1640 reveals azithromycin efficacy against carbapenem-resistant Acinetobacter baumannii and predicts in vivo outcomes in Galleria mellonella. The microb is antimicrob. The agents Chemother. 67 were named e00320 and e00322.

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Source: A broad-spectrum lasso peptide antibiotic targeting the bacterial ribosome

Bioinformatics of Bacterial Pathogens: Benchmarking High-Precision Sequencing with Nanopore Assemblies

Chen, Z., Erickson, D. L. & Meng, J. Benchmarking hybrid assembly approaches for genomic analyses of bacterial pathogens using Illumina and Oxford Nanopore sequencing. BMC Genomics 21, 631 (2020).

Blin, K. et al. antiSMASH 7.0: new and improved predictions for detection, regulation, chemical structures and visualisation. Nucleic Acids Res. 51, W46–w50 (2023).

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Source: A broad-spectrum lasso peptide antibiotic targeting the bacterial ribosome

Structural insights into the mechanism of overcoming Erm-mediated resistance by hygromycin and ribosome complexes

Syroegin, E. A., Aleksandrova, E. V. & Polikanov, Y. S. Insights into the ribosome function from the structures of non-arrested ribosome–nascent chain complexes. Nat. Chem. 15, 143–152, 2053.

C. W. Chen, a member of the research team. Structural insights into the mechanism of overcoming Erm-mediated resistance by macrolides acting together with hygromycin-A. Nat. Commun. 14, 4196 (2023).