Duke researchers identify hidden chlamydial cloaking device

Chlamydia, the main cause of bacterial sexually transmitted infections, evades detection and eradication within human cells using a masking device. But researchers at Duke University have recognized the fringe of the invisibility cloak and now hope they can unravel it.

To enter the cell and reproduce peacefully, many pathogenic bacteria, including chlamydia, cover themselves with a piece of cell membrane, forming a free-floating bubble inside the cells called a vacuole or, in the case of chlamydiaAnd the Insertion. Chlaymydia appears to be particularly effective at evading cell autoimmunity, allowing the infection to persist for months.

The Duke team, led by graduate student Stephen Walsh and Jorn Kurz, Ph.D., associate professor of molecular genetics and microbiology at Duke School of Medicine, wanted to know how anonymity worked.

We knew there was potential to kill chlamydia, but when we did experiments with the human-adapted form, Chlamydia trachomatis, this was very good at growing in human cell cultures.”

Jörn Kors, PhD, associate professor of molecular genetics and microbiology, Duke School of Medicine

Even after the scientists used an immune stimulant to alert the cell’s defense systems to the presence of chlamydia, nothing happened. “We said, there’s the pathogen. Our defense system should see it. Why doesn’t it?”

They performed their experiments again using a mouse-adapted version of the chlamydia bacterium in human cells to see how the cell’s immune system responds to non-human pathogens.

“Humans, they don’t get chlamydia in mice because it has evolved with mice and human chlamydia has evolved with humans,” Coyers said. “So there’s this really subtle adaptation that the pathogen underwent.” The mouse version of the bacterial inclusion was easily identified and characterized for destruction in human cells.

Chlamydia Chlamydia trachomatis is very good at avoiding human reactions, Coers said. “It still causes inflammatory disease, but it’s a very slow disease.”

The evolutionary arms race between the immune system and pathogens has been going on for millions of years. Adaptation of mouse and human chlamydia “They have a common ancestor,” Kors said. “However, that common ancestor may go way back when humans and rodents essentially separated from each other. That’s a long time for the bacteria to fine tune their interaction with the host species.”

Working with fellow Duke MGM Rafael Valdivia and Robert Bastidas, the researchers conducted a large genetic screen for chlamydia that identified a protein, GarD (gamma resistance determinant), that appeared to impede the host cell’s ability to identify a chlamydia insert for destruction by the immune system.

The GarD gene mutation made the bacteria vulnerable. “GarD is the stealth factor,” Coers said.

Specifically, GarD interferes with the ability of a giant signaling protein called RNF213 or mysterin to sense small portions of bacterial molecules emerging from the shell of a candle. “The RNF213 is basically the eyes of the immune system,” Kors said. After Mysterin was blinded in this way, the signal of weakened immunity and destruction never began.

The interior of the cell is filled with these tiny bubbles of membrane-covered vacuoles. Most of them are friends, but some, like chlamydia Implication, they are enemies.

“There are many different types of membranes and vacuoles that live inside the cell,” Kors said. “How does the immune system find the rare vacuole that contains the pathogen? In the case of chlamydia, we don’t really have an answer to that question. But whatever it is, we think this enzyme (mysterin) sees it.”

Unfortunately, that’s all this story has to offer at the moment, Kors said. This is a fascinating new insight into a malignant infection, but it is several steps away from a cure. Researchers still need to figure out how Mysterin sees those bacterial particles in the first place and how GarD Mysterin blinds.

“If you can find a mechanism to deactivate GarD, you can transform human chlamydia “In murine chlamydia,” Koyers said. “This will allow us to harness the powers of our immune system to clear the infection.”

new chlamydia The infection occurs in 200,000 Americans annually and is often asymptomatic for months or even years during sexual transmission. Over time, an untreated infection can lead to pelvic inflammatory disease, ectopic pregnancy, and female infertility.

The US Centers for Disease Control recommends screening for young women Chlamydia annually.

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Journal reference:

Walsh, S.C., et al. (2022) The Bacterial Effector GarD Shields Chlamydia Trachomatis Inclusoins from RNF213-mediated Destruction and Destruction. Host cell and microbe. doi.org/10.1016/j.chom.2022.08.008.

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