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Effective phage cocktails consisting of multiple virus types are essential for successful phage therapy against pandrug-resistant pathogens, including Salmonella enterica serovar (S.) Typhimurium. Here we show that a Salmonella phage, F118P13, with non-productive infection and a lytic phage, PLL1, combined to inhibit pandrug-resistant S. Typhimurium growth and significantly limited resistance to phages in vitro. Further, intraperitoneal injection with this unique phage combination completely protected mice from Salmonella-induced death and inhibited bacterial proliferation rapidly in various organs. Furthermore, the phage combination treatment significantly attenuated the inflammatory response, restored the generation of CD4+ T cells repressed by Salmonella, and allowed macrophages and granulocytes to participate in immunophage synergy to promote bacterial clearance. Crucially, the non-productive phage F118P13 is less likely to be cleared by the immune system in vivo, thus providing an alternative to phage cocktail against bacterial infections. [ABSTRACT FROM AUTHOR]

Background: Osimertinib-based therapy effectively improves the prognosis of lung adenocarcinoma (LUAD) patients with epidermal growth factor receptor mutations. However, patients will have cancer progression after approximately one year due to the occurrence of drug resistance. Extensive evidence has revealed that lipid metabolism and tumor-associated macrophage (TAM) are associated with drug resistance, which deserves further exploration. Methods: An osimertinib resistance index (ORi) was built to investigate the link between lipid metabolism and osimertinib resistance. The ORi was constructed and validated using TCGA and GEO data, and the relationship between ORi and immune infiltration was discussed. Weighted gene co-expression network analysis based on the M2/M1 macrophage ratio determined the hub gene TIAM2 and the biological function of TIAM2 in LUAD was verified in vitro. Results: ORi based on nine lipid metabolism-related genes was successfully constructed, which could accurately reflect the resistance of LUAD patients to osimertinib, predict the prognosis, and correlate with M2-like TAM. Additionally, TIAM2 was found to increase osimertinib tolerance, enhance cell motility, and promote M2-like TAM polarization in LUAD. Conclusions: The lipid metabolism gene is strongly connected with osimertinib resistance. TIAM2 contributes to osimertinib resistance, enhances cell motility, and induces M2-like TAM polarization in LUAD. [ABSTRACT FROM AUTHOR]