Abstract
PURPOSE: Antibiotic resistance (AR) is an escalating worldwide health emergency, requiring inventive strategies for antibiotic treatment. This review examines the tactics used in designing smart antibiotics, with a specific emphasis on the mechanism of action of lolamicin, a newly developed microbiome-sparing antibiotic. METHODS: We review the recent advances in smart antibiotic development, particularly those aiming to preserve the gut microbiome while effectively targeting pathogens. The study focuses on lolamicin's selective targeting mechanism, its inhibition of the LolCDE complex in Gram-negative bacteria. RESULTS: Lolamicin works by blocking the LolCDE complex, which is crucial for transporting lipoproteins in Gramnegative bacteria. It offers a significant improvement compared to conventional antibiotics and other microbiomesparing options by safeguarding the microbiome and reducing the development of resistance. However, its limited range of effectiveness - namely against certain harmful bacteria such as Pseudomonas aeruginosa - and the possibility of bacteria becoming resistant to it, remain areas of concern. CONCLUSION: Lolamicin presents a hopeful resolution by selectively attacking Gram-negative bacteria while leaving the beneficial gut flora unharmed. Further investigation and rigorous clinical testing are essential to fully harness its promise and confirm its long-term utility in combating antibiotic resistance.