New antibiotic spares the gut

A team led by Paul Hergenrother at the University of Illinois Urbana-Champaign has discovered a new antibiotic that exclusively targets gram-negative bacteria and avoids wiping out the ecosystem of other microbes that flourishes in the gut. Lolamicin, as the group has named the compound, targets part of the localization of lipoprotein (Lol) pathway, a protein system that's responsible for the transport of lipoproteins to the outer membrane in gram-negative bacteria. Specifically, the molecule interferes with the LolCDE complex, disrupting its ability to release outer-membrane-specific lipoproteins from the inner membrane ( Nature 2024, DOI: 10.1038/s41586-024-07502-0 ). Lolamicin was especially effective against Escherichia coli , Klebsiella pneumoniae , and Enterobacter cloacae in mice. Importantly, the antibiotic also appeared to leave commensal bacteria alone, since many are gram-positive bacteria that don't have the Lol complex that lolamicin exploits. That spared the mice from gut dysbiosis—a common side effect of broad-spectrum antibiotics—and prevented colonization