Tag Archives: listeria

CFTR aids Listeria escape into cell cytosol

Courtesy of CDC/ Dr. Balasubr Swaminathan; Peggy Hayes

The intracellular pathogen Listeria monocytogenes must escape the vacuole formed during entry into the host cell to replicate in its preferred environment—the cell cytosol—and continues its life cycle. Although the pore-forming bacterial toxin listeriolysin O is vital for Listeria escape and virulence, new research by Radtke and colleagues published online in PNAS shows that a host cell protein, CFTR (cystic fibrosis transmembrane conductance regulator, which forms a chloride ion channel that, incidentally, when dysfunctional results in cystic fibrosis), promotes escape of L. monocyotgenes from intracellular vacuoles.

Radtke et al. reasoned that, as the intravacuolar environment is dynamic and likely modulated by a variety of proteins, regulation of ion flux whilst Listeria is inside a vacuole could affect its subsequent escape from this membrane-bound organelle. The researchers confirmed that CFTR was endogenously expressed by mouse macrophages and addition of a CFTR inhibitor did not affect uptake of Listeria into host cells but did reduce the number of intracellular bacteria, indicating that the bacteria might be trapped within the vacuole. Using macrophages isolated from either wild-type mice or mice carrying the CFTR mutation associated with human cystic fibrosis, they found that defects in CFTR led to delayed intracellular replication (indicative of a defect in vacuole escape). Finally, the researchers conclude that CFTR potentially promotes escape of Listeria by controlling the flux of chlorides into the vacuole—a high chloride concentration seems to increase both the oligomerisation and haemolytic activity of listeriolysin O, the key bacterial toxin needed for escape.

 

Little is known about the role of ion transport in the context of bacterial infection and it would be interesting to see whether other ion channels and transporters also contribute to the virulence of Listeria and other intracellular bacteria.

 

 ResearchBlogging.orgRadtke, A., Anderson, K., Davis, M., DiMagno, M., Swanson, J., & O’Riordan, M. (2011). Listeria monocytogenes exploits cystic fibrosis transmembrane conductance regulator (CFTR) to escape the phagosome Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.1013262108

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