Unveiling the Mechanism: Unraveling How Disease-Causing Microbes Prepare for an Attack

Eating the wrong microbe might result in a hospital stay, with lots of bacterial needles invading your body. These microscopic structures inject harmful proteins into our cells. Scientists have recently discovered how these bacteria manage to load their nanoscopic needles with these pathogenic proteins.

The study, published in Nature Microbiology on January 3, discusses a system that is visually compared to a shuttle bus with respect to how it functions within bacteria. Proteins within the bacteria move randomly, gathering proteins that are later injected and depositing them at the 'syringe'-like structures. This understanding of bacterial processes could lead to the development of tools that disrupt or use them for medical treatments, including targeting cancer cells without affecting healthy tissue.

Microbiologists previously didn't know of this "novel molecular mechanism" for transporting proteins to the 'syringes', says Andreas Diepold of the Max Planck Institute for Terrestrial Microbiology in Germany. He adds that these microscopic structures, known as type-III secretion systems (T3SS), look like hollow needles and cover the entire surface of a bacterium.

Though the protein structure of these nanoscale needles is well-known, how they recruit whatever is injected remains a mystery. Earlier research hinted that a set of proteins located at the base of the T3SS and connected to the bacterial membrane might behave as a selecting platform, collecting and loading proteins into the syringe.

Diepold and his team provided another theory that these components do not remain stationary at the needle base, rather they move randomly within the bacterial cell membrane, collecting and dropping target proteins like a shuttle bus. A new study further examined this theory by tracking the movement of individual sorting platform proteins in a type of stomach bug using fluorescence microscopy. The results indicated that these shuttle-bus proteins do not only move around but also pick up passengers along the way.

Kelly Hughes, a microbial geneticist at the University of Utah, applauded the study for being completely based on living cells, saying, “You get these beautiful pictures. And you know, a picture's worth a thousand words.”

Understanding these microscale needles further will allow scientists to manipulate them or develop new types of antibacterials. These needles are common across a variety of bacterial species, which makes them an attractive choice for creating new drugs. They also show great potential for use in medicine and biotechnology. However, the mechanisms by which bacteria use these syringes are yet to be fully understood. These include the process through which proteins are pushed through the needles and how the protein load recognises its targets. “We want to understand the riddle of how these systems work,” Diepold concludes, “We want to understand which solutions evolution came up with to allow bacteria to infect us.”