Search

Immune potentiators, termed adjuvants, trigger early innate immune responses to ensure the generation of robust and long‐lasting adaptive immune responses of vaccines. Presented here is a study that takes advantage of a self‐assembling small‐molecule library for the development of a novel vaccine adjuvant. Cell‐based screening of the library and subsequent structural optimization led to the discovery of a simple, chemically tractable deoxycholate derivative (molecule 6, also named cholicamide) whose well‐defined nanoassembly potently elicits innate immune responses in macrophages and dendritic cells. Functional and mechanistic analyses indicate that the virus‐like assembly enters the cells and stimulates the innate immune response through Toll‐like receptor 7 (TLR7), an endosomal TLR that detects single‐stranded viral RNA. As an influenza vaccine adjuvant in mice, molecule 6 was as potent as Alum, a clinically used adjuvant. The studies described here pave the way for a new approach to discovering and designing self‐assembling small‐molecule adjuvants against pathogens, including emerging viruses. [ABSTRACT FROM AUTHOR]

WHO considers colistin as a highest priority critically important drug for human health, and occurrence of colistin-resistant bacteria in livestock is of health concern. The current study determined occurrence of colistin-resistant Escherichia coli in pigs and workers at pig farms in Vietnam, and investigated the genetic background for resistance. Colistin-resistant E. coli were detected from pigs in 53/116 (45.7%) farms, and from workers taking care of the pigs in 21/94 (22.3%) farms. Colistin-resistant isolates showed MIC to colistin between 4-16 mg/L, they were multidrug resistant (99%) and resistance was caused by the presence of mcr-1 genes in 97/102 (95.1%) E. coli from pigs and in 31/34 (91.1%) isolates from humans. mcr-1 is considered a plasmid-encoded gene, but this was not confirmed in the current investigation. In total, one pig isolate carried both mcr-1 and mcr-3 genes, whereas mcr-2, mcr-4 and mcr-5 genes were not detected. Shared resistance profiles between pig and human isolates on the same farm was only observed in four farms. The study showed that commensal E. coli from pigs in Vietnam constitute a reservoir for colistin-resitant E. coli , however, further studies are needed to confirm that mcr genes are associated with plasmids and their importance for human health., Competing Interests: None declared., (© The Author(s) 2020. Published by Oxford University Press on behalf of FEMS.)