Antibiotic-induced disruption of the gut microbiome can compromise health and make people more susceptible to opportunistic infection by pathogens like C. difficile. The widespread rise of superbugs resistant to antibiotics further complicates their use.

Researchers from the University of Illinois Urbana-Champaign now say they've developed a next-generation antibiotic that reduces or eliminates multidrug-resistant bacterial infections while leaving healthy gut bacteria intact.

"People are starting to realize that the antibiotics we've all been taking – that are fighting infection and, in some instances, saving our lives – also are having these deleterious effects on us," said Paul Hergenrother, a chemistry professor at the University and the study's corresponding author. "They're killing our good bacteria as they treat the infection. We wanted to start thinking about the next generation of antibiotics that could be developed to kill the pathogenic bacteria and not the beneficial ones."

Bacteria are classified as gram-positive or gram-negative based on their cell membrane composition. Gram-positive bacteria don't have an outer membrane, whereas gram-negative bacteria have two – external and internal – making them harder to kill. Most antibiotics kill only gram-positive or both bacterial classes (the latter are called 'broad-spectrum'). There are few gram-negative-only antibiotics available, even though gram-negative bacteria resistant to multiple antibiotics are widespread.

A significant percentage of the gut microbiome is composed of gram-negative bacteria, which are targeted by the few available gram-negative-only antibiotics approved for clinical use. To combat the problem of these antibiotics indiscriminately targeting gut bacteria, the researchers focused on inhibiting the Lol (localization of lipoprotein) system. Exclusive to gram-negative bacteria, the Lol system is an essential mechanism responsible for trafficking lipoproteins from the inner to the outer membrane to aid bacterial growth. The system is also genetically different in pathogenic and beneficial microbes. After trialing different compound structures, the researchers arrived at the aptly named 'lolamicin.'