RT Journal Article
SR Electronic
T1 Genome-wide screen identifies curli amyloid fibril as a bacterial component promoting host neurodegeneration
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.03.22.436366
DO 10.1101/2021.03.22.436366
A1 Chenyin Wang
A1 Chun Yin Lau
A1 Fuqiang Ma
A1 Chaogu Zheng
YR 2021
UL http://biorxiv.org/content/early/2021/03/22/2021.03.22.436366.abstract
AB Growing evidence indicate that gut microbiota play a critical role in regulating the progression of neurodegenerative diseases, such as Parkinson’s disease (PD). The molecular mechanism underlying such microbe-host interaction is unclear. In this study, by feeding C. elegans expressing human α-syn with E. coli knockout mutants, we conducted a genome-wide screen to identify bacterial genes that promote host neurodegeneration. The screen yielded 38 genes that fall into several genetic pathways, including curli formation, lipopolysaccharide assembly, adenosylcobalamin biosynthesis among others. We then focused on the curli amyloid fibril and found that genetically deleting or pharmacologically inhibiting the curli major subunit CsgA in E. coli reduced α-syn-induced neuronal death, restored mitochondrial health, and improved neuronal functions. CsgA secreted by the bacteria colocalized with α-syn inside neurons and promoted α-syn aggregation through cross-seeding. Similarly, curli also promoted neurodegeneration in C. elegans models of AD, ALS, and HD and in human neuroblastoma cells.Competing Interest StatementThe authors have declared no competing interest.