Lipid Droplet-Enriched Luminogens Enable Adoptive Macrophage Transfer for Treatment of Bacterial Sepsis

MRSA-induced sepsis poses a significant threat to human health. In clinical practice, the primary approach for sepsis treatment remains the use of antibiotics to control bacterial infections. However, the widespread and prolonged use of antibiotics has led to increased bacterial resistance, rendering conventional antibiotics less effective. Here, we report the design and development of a novel antibiotic that differs from traditional bactericidal mechanisms. This antibiotic employs a dual-targeting strategy by disrupting bacterial membrane integrity and binding to bacterial DNA, thereby effectively eliminating bacteria. This approach enhances antibacterial efficacy while reducing the likelihood of resistance development. Overall design: The impact of the novel antibiotic TPA2PyPh on gene expression in methicillin-resistant Staphylococcus aureus (MRSA) was investigated. MRSA (~105 CFU/mL) was incubated in LB culture medium containing 0.5 µM TPA2PyPh (1/2 × MIC) at 37 °C for 24 hours. Following incubation, the bacteria were harvested for total RNA extraction using the TRIzol reagent (Invitrogen, CA, USA). The control group was subjected to the same conditions without TPA2PyPh treatment.