Antibiotics kill disease-causing bacteria as well as beneficial bacteria living in the gut, negatively affecting the microbiome that maintains health. However, according to an article published on New Atlas citing the journal Nature, a new study has produced an antibiotic that specifically targets bacteria that are difficult to kill while leaving good gut bacteria unharmed. Disruption of the gut microbiome caused by antibiotics can harm health and make patients more susceptible to opportunistic infections from pathogens such as Clostridium difficile. The widespread rise of antibiotic-resistant superbugs complicates their use.
Researchers from the University of Illinois have successfully developed a next-generation antibiotic that reduces or eliminates multi-drug resistant bacterial infections while preserving healthy gut bacteria. Paul Hergenrother, a chemistry professor at the University of Illinois and a co-researcher of the study, stated, "Many are beginning to understand that antibiotics, which everyone takes to eradicate infections and in some cases save their lives, also have harmful effects on public health," noting that they "kill good bacteria in the body while treating infections." Thus, the research team aimed to think of the next generation of antibiotics that could be developed to kill pathogenic bacteria while sparing beneficial bacteria.
Bacteria are classified as gram-positive or gram-negative based on their cell membrane structure. Gram-positive bacteria lack an outer membrane, while gram-negative bacteria have two membranes—an outer and an inner—making them harder to kill. Most antibiotics kill only gram-positive bacteria or both types, referred to as "broad-spectrum." There are very few antibiotics available that specifically act on gram-negative bacteria, despite the widespread prevalence of multi-drug-resistant gram-negative bacteria.
**Lulamycine Compound**
A significant portion of the gut microbiome consists of gram-negative bacteria, which are targeted by the few available antibiotics that work solely on gram-negative bacteria and are approved for clinical use. To address the issue of these antibiotics indiscriminately targeting gut bacteria, researchers focused on inhibiting the Lol lipid protein localization system, which is exclusive to gram-negative bacteria and represents a critical mechanism responsible for transporting lipoproteins from the inner membrane to the outer membrane to aid bacterial growth. The system also differs genetically in pathogenic and beneficial microbes. After experimenting with different compound structures, researchers aptly named the antibiotic "lulamycine."
**Treatment of Sepsis and Pneumonia**
In laboratory tests, the "lulamycine" compound showed effectiveness at higher doses, killing up to 90% of Escherichia coli and Klebsiella pneumoniae or Clostridium difficile, all of which are multi-drug resistant and major causes of hospital-associated infections. Using infected mouse models with sepsis, which can lead to fatalities in humans, and acute pneumonia, treatment with "lulamycine" achieved 100% success in sepsis cases and 70% success in pneumonia cases, without any negative impact on many groups of beneficial gut bacteria. Researchers even noted that "in the treatment group with 'lulamycine,' the richness of species [bacterial groups] was maintained throughout the treatment and recovery period."
**Further Research Needed**
While the findings are extremely promising, it is unlikely that the "lulamycine" antibiotic will appear on pharmacy shelves anytime soon, as years of additional research are needed to test the drug against other bacterial strains and determine its toxicity. As with any new antibiotic, it will need to be evaluated to assess how quickly resistance develops. However, the study demonstrates that it is possible to develop antibiotics specifically targeting gram-negative bacteria, some of the hardest types of bacteria to kill, while deliberately avoiding any negative impact on good bacteria.
