Study suggests targeting protein transport channel to thwart pathogen

SAN FRANCISCO, Sept. 2 (Xinhua) -- Researchers at Oregon State University (OSU) have found that a bacterium, Mycobacterium avium, or M. avium, could be halted by disrupting the distribution channels the organism uses to access the nutrient-rich cytoplasm of its host cell.

As the most common pathogen among non-tuberculosis mycobacteria and being highly opportunistic, M. avium invades and proliferates within a variety of human cells; resides in a cytoplasmic vacuole and survives by remodeling its vacuolar compartment and resisting its host's antimicrobial mechanisms.

"Most bacteria that grow in phagocytic cells export their effector proteins that impair or redirect macrophage function by using a needle-like apparatus that perforates the vacuole membrane and delivers virulence-associated molecules to the cytoplasm," explained Luiz Bermudez of OSU's College of Veterinary Medicine. "But mycobacteria don't have that, so the question has always been, how do all these proteins get exported, how do they cross the vacuole membrane?"

Mycobacteria likely do so because proteins of the pathogen dock to transport proteins of the phagosome in the host cell in a way that allows for the efficient secretion of effector proteins.

Detailed in a paper published in Scientific Reports, Lia Danelishvili, also of the OSU College of Veterinary Medicine, identified voltage-dependent anion channels, or VDACs, as a possible means of exporting those proteins. Both Bermudez and Danelishvili are co-corresponding author of the paper.

"We found that yes, mycobacteria use surface proteins to bind to the VDAC," Bermudez was quoted as saying in a news release from OSU this week. "But although we tried to see if the proteins of the mycobacterium were exported by the VDAC, we couldn't show that. However, we did show that another component of the cell wall of the mycobacterium, lipids, are exported by that mechanism."

The findings, according to the researchers, are important because they suggest a new therapeutic target for one of the leading causes of bacterial infection in patients with HIV/AIDS.