Mechanistic basis of host infection and intracellular development in microsporidia
Microsporidia are emerging pathogens of high priority that infect humans, and most animals. Microsporidiosis can be life-threatening and cause severe damage in the eyes, brain, muscles, respiratory, and urinary tracts. These obligate intracellular parasites also present a unique case of reductive and divergent evolution. They possess the smallest eukaryotic genome and unique cellular features such as the smallest eukaryotic cytoplasmic ribosomes and a specialised infection apparatus, the polar tube. Inside the host, microsporidia replicate through distinct life stages to form infective spores that are released into the environment upon host cell lysis. However, the molecular events involved in the pathogen’s commitment to each life stage, host cell lysis, formation, and eversion of the polar tube, remain unclear. This lacunae in understanding microsporidia are due to a lack of biochemical or structural data and the absence of systematic in vivo studies. Thus, studying this medically and economically relevant pathogen is critical for designing drugs and preventive regimes to curtail their transmission. Towards this, MsInfection aims to provide the first comprehensive and mechanistic insights into microsporidian life-cycle progression and host cell invasion. The life cycle stages of microsporidia species with varied tissue tropism will be analysed structurally and transcriptomically at the single-cell level, using Electron Microscopy (EM) and single cell-RNA sequencing (scRNA-seq). A combination of these transformative technologies will enable a systematic determination and visualisation of the molecular events driving intracellular development, and the assembly of infection apparatus and tissue niche selection.