At left: A wild type Chlamydia (green) surrounded by the GarD protein (red) that cloaks it from detection inside human cells. Right: Chlamydia with GarD knocked out (green) are enveloped by the antimicrobial proteins ubiquitin (yellow) and RNF213 (magenta). Credit: Stephen C. Walsh, Duke University
Key Points:
- A large genetic screen of Chlamydia identified a protein that could be exploited to develop a treatment to clear the infection.
- Research shows mutating the genes leaves the bacteria vulnerable.
- The team is working to find a mechanism to deactivate the protein, turning it into a less harmful version that can be easily treated.
Chlamydia, the leading cause of sexually transmitted bacterial infections, evades detection and elimination inside human cells by use of a cloaking device. The pathogenic bacteria cloak themselves in a piece of the cell’s membrane, forming an intracellular free-floating bubble called an inclusion. Chlaymydia’s cloak appears to be especially effective at evading the cell’s built-in immunity, allowing the infection to last for months.
Now, a team of Duke University researchers is ripping that invisibility cloak off to get a better understanding of the persistent STF.
According to their study published in Cell Host & Microbe, the researchers ran a large genetic screen of Chlamydia that identified a protein, GarD (gamma resistance determinant), that appeared to be blocking the host cell’s ability to mark a Chlamydia inclusion for destruction by the immune system. GarD interferes with the ability of a giant signaling protein called RNF213, or mysterin, to sense small bits of bacterial molecules poking out of the shell of the inclusion.
When the researchers mutated GarD, the bacteria were left vulnerable.
“GarD is the stealth factor,” said study author Jörn Coers, associate professor of molecular genetics and microbiology at Duke. “RNF213 is basically the eyes of the immune system. Having blinded mysterin in this fashion, the signal for immune flagging and destruction is never started.”
The new study provides key insight into Chlamydia infection, but much more work is needed before the data can be leveraged into a therapy. Researchers still need to figure out how mysterin sees those bacterial molecules in the first place and how GarD blinds mysterin.
“If you could find a mechanism to deactivate GarD, then you can turn human Chlamydia into mouse Chlamydia,” said Coers. “That would allow us to harness the powers of our own immune system to clear infection.”
Information provided by Duke University.