How E. coli switches from "attack" mode to "colonize" mode
There's a delicate ecosystem thriving in your gut right now, but all it takes is a bad burrito to throw it off-kilter. Just how pathogens like E. coli take hold and trash the place isn't well understood, but now researchers from the Hebrew University of Jerusalem have studied how the bacteria senses its surroundings and in response, switches its gene expression from "attack mode" to "colonize mode."
Gastroenteritis, or infectious diarrhea, is usually caused by eating bad food or drinking contaminated water, so it's a particular problem for the developing world. While a range of microorganisms can trigger the illness, one of the most common is the bacteria E. coli, which latches onto the intestinal wall with its hair-like pili and causes inflammation and diarrhea.
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Once the bug attaches itself to the host cell, it uses a tiny syringe-like appendage called a type III secretion system (T3SS) to inject certain proteins into the intestinal cell. Called effectors, the injected proteins suppress the host's immune response, allowing the bacteria to thrive and begin to reproduce.
"Several effectors function to intercept signaling pathways involved in detecting the pathogen, and thus the host cannot 'see' that it is under attack," Ilan Rosenshine, lead researcher on the study, tells New Atlas. "This is clearly beneficial for the bacteria since the infected cells are not mounting a counter-attack. During the initial attack phase the bacteria use an 'attack' gene-expression program, but after attachment and effectors injection, the bacteria need to change the program to a 'colonization' gene-expression program."
On glowing green and genes
It's this latter process, and just how bacteria make the shift between modes, that remained a mystery to scientists. To shed some light on that, the researchers engineered a pathogenic strain of E. coli so that when a gene associated with the "colonization phase" is activated, a particular protein is expressed that then stains the bacteria bright green. When studied under a microscope, the scientists found that only the E. coli that had attached itself to intestinal cells were glowing green, while those that were still loose were not fluorescent.
On closer inspection, the researchers singled out a protein that seems to be responsible for changing the gene expression mode. CesT is a "chaperone" protein, whose first job inside the bacterium is to bind to the effectors and ensure they can be easily injected into the host cell. When it finishes that task, the protein stays behind in the bacteria and starts on its secondary function: with no more effectors to bind to, it instead binds to a protein called CsrA. This protein also usually drives the bacteria in its attack mode, but when CesT binds to it, that process is interrupted, and the bacteria's gene expression is reprogrammed. The E. coli switches away from attacking the host to focus on its own virulence and metabolism instead, helping the bug colonize the gut environment.
This discovery could help scientists find new ways to fight off bacterial infection, but the team says there is still more work to be done in determining exactly which genes in the bacteria are affected, and what other effects that could have.
"The next steps include mapping in detail the genes that change their expression upon attachment, and describing the precise effects of this expression remodeling," said Rosenshine in a statement. "Another important issue is testing whether similar regulation is involved in the infection processes of other pathogens."
The research was published in the journal Science.
Source: Hebrew University of Jerusalem