Project description:Humans and microorganisms, both symbiotic and pathogenic, have evolved means to communicate through the dissemination of biological signals. In addition to small molecules and proteins, mobile small RNAs (sRNAs) have recently emerged as signal molecules that mediate inter-species crosstalk by functional RNA interference (RNAi). However, the trafficking of sRNAs between humans and microorganisms, as well as the resulting biological consequences, remains unexplored. Here, we report that human cells secrete exosomes to deliver sRNAs into bacteria and induce bacterial gene silencing. The unprecedented RNAi in bacteria is accomplished primarily through translational repression without mRNA degradation, for which the participation of human AGO2 proteins co-transferred with sRNAs is essential. Exosome-mediated bacterial RNAi was further applied to fight superbug infection by targeting drug-resistance genes in a mouse model. Our discovery of this unique exosome-mediated sRNA delivery and gene silencing in bacteria paves the way to understanding and manipulating the cross-kingdom communication between human hosts and intestinal microbiota, as well as between humans and pathogenic bacteria.
Project description:Leaves are colonised by a complex mix of microbes, termed the leaf microbiota. Even though the leaf microbiota is increasingly recognised as an integral part of plant life and health, our understanding of its interactions with the plant host is still limited. Here, mature, axenically grown Arabidopsis thaliana plants were spray-inoculated with diverse leaf-colonising bacteria. Whole transcriptome sequencing revealed that four days after inoculation, leaf transcriptional changes to colonisation by non-pathogenic and pathogenic bacteria differed in strength but not in the type of response.
Project description:Ionophores are antibacterial compounds that affect bacterial growth by changing intracellular concentrations of the essential cations, sodium and potassium. They are extensively used in animal husbandry to increase productivity and reduce infectious diseases. Given their widespread usage, it is important to determine the potential negative consequences of ionophore use on human and animal health. In this study, we demonstrate that exposure to the ionophore monensin can select for resistant mutants in the human and animal pathogen Staphylococcus aureus, with a majority of the resistant mutants showing increased growth rates in vitro and/or in mice. Whole-genome sequencing and proteomics analysis of the resistant mutants show that the resistance phenotype is associated with de-repression of de novo purine synthesis, which could be achieved through mutations in different transcriptional regulators including mutations in the gene purR, the repressor of the purine de novo synthesis pathway. This study shows that mutants with reduced susceptibility to the ionophore monensin can be readily selected and highlights an unexplored link between ionophore resistance, purine metabolism and fitness in pathogenic bacteria.
Project description:Leaves are colonised by a complex mix of microbes, termed the leaf microbiota. Even though the leaf microbiota is increasingly recognised as an integral part of plant life and health, our understanding of its interactions with the plant host is still limited. Here, mature, axenically grown Arabidopsis thaliana plants were spray-inoculated with diverse leaf-colonising bacteria. Whole transcriptome sequencing revealed that four days after inoculation, leaf transcriptional changes to colonisation by non-pathogenic and pathogenic bacteria differed in strength but not in the type of response. Inoculation of plants with different densities of the non-pathogenic bacterium Williamsia sp. Leaf354 showed that high bacterial titers caused disease phenotypes and led to severe transcriptional reprogramming with a strong focus on plant defence. This SuperSeries is composed of the SubSeries listed below.