Amyloid-β peptide promotes bacterial aging

The pathological hallmark of Alzheimer's disease is brain deposition of senile plaques composed predominantly of amyloid fibrils. These conformational structures, characteristic of many other human disorders, are formed mainly by the amyloid-β peptide Aβ42. This peptide, which is primarily disordered and soluble as an isolated monomer, can undergo an aggregation and fibrillation process that results in these amyloid protein deposits. When the amyloid-β peptide is expressed in bacteria, a similar conformational change occurs resulting in the formation of inclusion bodies that resemble structurally to human amyloid fibrils. Here we demonstrate that the kinetics of aggregation from the unstructured state depends on the aminoacid sequence and its intrinsic aggregation propensity. Furthermore, we observe that these amyloid-like deposits impair cell division promoting aging and, more interestingly, we establish a correlation between this deleterious effect and the aggregation propensity of the expressed peptide. Finally, we also show that the interaction of the amyloid-β peptide with molecular chaperones alleviates cell aging phenotype probably by decreasing the aggregation rate. The findings presented here have implication in understanding the molecular mechanisms of how the aggregation of a disordered peptide, like the amyloid-β, can drive bacterial aging.