Forced Feeding

Editor's choice in drug development

By | February 1, 2012

image: Forced Feeding HUNGRY FOR PROTEIN: Colored scanning electron micrograph (SEM) of a group of Legionella pneumophila bacteria. CDC Public Health Image Library

HUNGRY FOR PROTEIN: Colored scanning electron micrograph (SEM) of a group of Legionella pneumophila bacteria. CDC PUBLIC HEALTH IMAGE LIBRARY

The paper

C.T.D. Price et al., "Host proteasomal degradation generates amino acids essential for intracellular bacterial growth," Science, 334:1553-57, 2011.

The finding

When University of Louisville's Yousef Abu Kwaik and colleagues stumbled upon a eukaryotic protein in Legionella bacteria, he suspected the prokaryotes had stolen the gene from its host to help it co-opt their eukaryotic prey–either an amoeba or a human cell. Their investigations revealed that the protein, called AnkB, forces the host cell to degrade its own proteins into amino acids to provide sufficient quantities of nourishment for the parasitic bacterium.

The digest

The protein AnkB was known to tag perfectly healthy proteins with ubiquitin–an address label that marks misfolded proteins for proteasomal degradation–but it was unclear how this process benefited the bacterium. And, although bacteria are known to steal nutrients, "such strategies vary a lot with the pathogen being studied, and we still do not know much about most of them," writes Rui Appelberg from University of Porto, Portugal, in an e-mail.

The food factory

"This bacterium really lives on an Atkins diet," says Abu Kwaik, consuming only proteins in the form of free amino acids. When researchers blocked the host cell's protein degradation machinery, replication of the Legionella ceased, only to be restarted if pure amino acids–in particular cysteine or serine–were added to the culture medium.

The application

Infection with Legionella can only occur by exposure to contaminated water. In theory, these water sources could be treated with currently available proteasome inhibitors to starve the bacteria to death, says Abu Kwaik.




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