Noteworthy
Amid the turmoil and uncertainty of our times, one fact is undeniable: microbes continue to evolve. Their very resilience and adaptability have led to the current crisis of antimicrobial resistance as microbes develop resistance to the antimicrobial drugs used to control them. Oblivious to geography or borders, the spread of resistant microbes has become a threat to human health. Future scenarios even envision rapidly escalating death tolls from our inability to efficiently manage microbial pathogens.
Tackling the antimicrobial resistance crisis requires multiple approaches. These range from understanding consumption trends and limiting use in sectors such as animal rearing, where resistance has escalated, to identifying new antibacterial compounds.
Lariocidin and its biosynthetic gene cluster. Source
A recent paper, the result of a multigroup collaboration (from McMaster University in Canada, Gerry Wright's group and from U. of Illinois at Chicago, the groups of Alexander Mankin, Nora Vazquez-Laslop and Yury Polikanov), reports on a novel broad-spectrum peptide antibiotic that targets the bacterial ribosome. The authors generated a collection of strains from which they prepared and screened extracts for antibacterial activity against Gram-negative strains. By aiming for slow-growing and potentially overlooked environmental strains and carefully teasing out activities in the extracts, they discovered the novel peptide antibiotic lariocidin (LAR). This peptide belongs to a group of natural products known as RiPPs that are synthesized via the ribosome from peptide-encoding genes. The precursor peptide generated is then post-translationally modified, in this case resulting in a lasso peptide with a characteristic 3D shape that makes these molecules highly stable.
Although many peptides with antimicrobial activity are known, LAR has unique properties. It is the only RiPP known to target the 30S ribosomal subunit. By doing so, it inhibits translation elongation and induces miscoding. This peptide also had broad-spectrum antimicrobial activity against both Gram-positive and Gram-negative bacteria.
It is encouraging to know that new antimicrobials can still be obtained by tweaking long-tried approaches based on culturing to screen environmental microbes. Hopefully, such discoveries will lead to the development of much-needed antibacterial drugs.
("Noteworthy" is the new format for STC's Thursday posts. Please read our Jan 20, 2025 post outlining this and other changes in our blog.)
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