Detecting pathogenic bacteria with a lol system based on Lol protein differences between Gram-negative bacteria and the gut microbiome

The bacteria have “multiple barriers that prevent antibiotic penetration”, says molecular biologist Zemer Gitai at Princeton University in New Jersey, who was not involved in the research. There are not many antibiotics that target Gram-negativebacteria. The few drugs that do also wreak havoc with the gut microbiome, allowing potentially deadly pathogens such as Clostridioides difficile to take over.

The authors of the study tried to find compounds that did not kill thebacteria but that did affect theLol system, a group of proteins exclusive to Gram-negativebacteria. Tinkering with those compounds produced one that the researchers called lolamicin, which “selectively kills pathogenic bacteria over non-pathogenic bacteria based on differences in Lol proteins between these bacteria”, says study co-author Paul Hergenrother, a chemist at the University of Illinois at Urbana-Champaign.

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How long does it take to discover an antibiotic? A Comment on Clostridioides difficile colonization in the era of genomic genome-wide sequencing

Gitai says that the study “proves the viability” of targeting the Lol system, but adds, “There is a long road from showing efficacy in mice to developing a drug for human use.”

Hiller also sounds a cautious note. The time from an antibiotic’s discovery to its approval for clinical use can be more than two decades, “and there is not much money to be made with a novel antibiotic”, he says. There are more than ten to twenty new Gram-negative antibiotics that have been discovered in the last ten years, but they have yet to be approved by the FDA.

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Source: A Gram-negative-selective antibiotic that spares the gut microbiome

Gram-negative antibiotic resistance in bacteria based on a novel leucyl-tRNA synthetase inhibitor DS86760016

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Source: A Gram-negative-selective antibiotic that spares the gut microbiome

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Source: A Gram-negative-selective antibiotic that spares the gut microbiome

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