Cholesterol helps bacterial toxins kill cells
doi:10.1038/nindia.2018.91 Published online 17 July 2018
Researchers from the Indian Institute of Science (IISc), Bangalore have found that cholesterol present in human or animal cell membranes actually aids certain bacterial toxins bind together to kill cells1.
Some bacteria produce toxins that can drill nano-sized holes in membranes of human or animal cells thus killing those cells. A number of steps precede the actual drilling by these pore forming toxins (PFT). The toxins bind to the membrane, find other toxin molecules around them, form ring-like structures and puncture a hole in the membrane. However, scientists did not yet know the mechanistic details of all these steps.
An interdisciplinary team of IISc scientists studied how a PFT called Cytolysin-A works in the bacteria Escherichia coli. They looked at how this toxin forms a ring-like pore composed of twelve protein molecules in the membrane of red blood cells. Investigating with a supercomputer and a microscope that can visualise single molecules of the toxin protein on the membrane, they found that cholesterol in the cell membrane acted like a ‘molecular glue’ between neighboring toxin molecules. This was critical for the formation of pores.
Due to the similarity of these toxins to proteins that cause neurodegenerative disorders such as Alzheimer's and Parkinson's, the findings can potentially be extrapolated to understand mechanisms associated with these diseases as well, the researchers report. "Our finding elucidates the basis for selective targeting of the toxin to eukaryotic membranes. Molecular engineering of these signatures could advance application of PFTs in cytolytic therapy," they say.
1. Sathyanarayana, P. et al. Cholesterol promotes cytolys in A activity by stabilizing the intermediates during pore formation. Proc. Natl. Acad. Sci. (2018) doi: 10.1073/pnas.1721228115