Scientists have made a breakthrough in the fight against harmful, antibiotic-resistant gram-negative bacteria. A study published in the journal Nature details a newly developed antibiotic compound called lolamicin that can kill pathogenic gram-negative bacteria, even strains resistant to many existing drugs, while leaving beneficial gut bacteria unharmed.

Gram-negative bacteria like E. coli and Klebsiella pneumoniae cause a range of dangerous infections from salmonella to cholera and can trigger life-threatening sepsis. These bacteria have robust defenses that prevent most antibiotics from penetrating them effectively. The few drugs that can target them also disrupt the gut microbiome, allowing opportunistic pathogens like C. difficile to proliferate.

The University of Illinois researchers discovered that by inhibiting the “Lol system” proteins unique to gram-negative bacteria, they could selectively kill these pathogens without harming other bacteria. Their compound lolamicin proved effective against over 130 multi-drug resistant bacterial strains in lab tests. Mice with antibiotic-resistant bloodstream infections all survived after lolamicin treatment, while 87% of untreated mice died within 3 days.

Crucially, lolamicin did not disrupt the gut microbiome like traditional antibiotics, preventing C. difficile overgrowth in the mice. “It selectively kills pathogenic bacteria over non-pathogenic bacteria based on differences in Lol proteins,” explained study co-author Paul Hergenrother.

While promising, experts caution the long road from mice studies to an approved human drug. The antibiotic development pipeline is difficult with little financial incentive presently.

However, if lolamicin or similar compounds can translate their success to human trials, it could dramatically improve treatment of deadly, increasingly resistant gram-negative infections without disrupting healthy gut flora. The study represents an important advance in that direction.

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