Genome-wide screen identifies curli amyloid fibril as a bacterial component promoting host neurodegeneration
Chenyin Wang, Chun Yin Lau, Fuqiang Ma, Chaogu Zheng
Abstract
Significance We investigate microbe–host interaction in the context of neurodegeneration by screening for Escherichia coli genes whose deletion alleviates Parkinson’s disease symptoms in the nematode Caenorhabditis elegans overexpressing human α-synuclein (α-syn, A53T). The screen yields 38 E. coli genes that promote neurodegeneration. Two of these genes, csgA and csgB , code for proteins that form curli, one type of bacterial amyloid fibers. Curli cross-seeds and colocalizes with α-syn both in C. elegans neurons and human neuroblastoma cells. Curli-induced α-syn aggregations down-regulate mitochondrial genes, causing energy failure in neurons. Moreover, we found that curli may have general effects in promoting neuropathologies induced by different aggregation-prone proteins, such as A-β in Alzheimer’s disease, Huntingtin in Huntington’s disease, and SOD1 in amyotrophic lateral sclerosis.