Some pathogens have been found to hide inside human cells in order to improve their chances of survival. A team of researchers, led by Prof. Marek Basler at the Biozentrum, University of Basel, has discovered a distinct strategy that certain bacteria employ to spread throughout the body without being detected by the immune system. Their study highlights the important role of a bacterial nanomachine in this process of infection.
rial nanomachine in this infection process.
When pathogens enter a cell, they can hide and evade the immune system, allowing them to spread within the body. One example of these bacteria is Burkholderia, specifically B. pseudomallei which causes melioidosis, a potentially fatal infectious disease found in tropical areas. This pathogen has a high mortality rate and is resistant to many antibiotics, making it a potential biothreat agent.
Another related but less harmful species is B. thai.Landensis, the group headed by Professor Marek Basler at the Biozentrum, University of Basel, has discovered a clever strategy used by the pathogen to spread within the tissue. According to Basler, “The bacteria possess a nano-sized speargun, known as the type VI secretion system (T6SS). Burkholderia utilizes this T6SS to move from one cell to another undetected by the immune system.” The recent publication of these findings in the journal Cell Host & Microbe challenges the current understanding of the T6SS’s role in Burkholderia infections. This pathogen uses a nanomachine to spread from cell to cell.
From previous research, it is well documented that these internal pathogens depend on an unconventional method of spreading: Once inside the cell, they utilize cellular components like actin to migrate to the cell membrane and create extensions into neighboring cells. With the help of their T6SS-speargun, the bacteria can also merge the two cells, enabling them to spread.
Unusual method of spreading without being noticed
Upon further investigation into the role of T6SS, the scientists have uncovered a previously unknown and distinct escape technique used by these bacteria. “We were taken aback to observe that Burkholderia is able to spread not only by causing cell fusion but also by directly transferring from one cell to another,” explains Dr. Miro Plum, the first author of the study. When the protrusion detaches from the cell membrane, it forms a vacuole within the adjacent cell. The pathogen inside the vacuole then escapes by using its T6SS to disrupt the surrounding cell membrane.
Surprisingly, this method of spreading also allows the bacteria to infect new cells without alerting the immune system. “Normally, infected cells detect invaders by sensing damaged cell membranes, which triggers immune responses to eliminate the pathogen,” Plum emphasizes. “However, cells are unable to do so when the pathogen spreads in this manner.”Detecting T6SS-disrupted membranes.” This means that the pathogen goes undetected and is able to infect new cells. Exploration of the survival tactics of intracellular pathogens Equipped with the T6SS nanomachine, Burkholderia bacteria can use both cell fusion and direct movement from one cell to another as a dual strategy. “Our findings improve our understanding of Burkholderia infections, especially its methods for spreading and evading the immune system,” Basler concludes. The researchers are now interested in investigating the specific mechanisms that trigger the T6SS assembly in bacteria inside the protrusions to gain a deeper understanding.Insights into the survival tactics of this intracellular pathogen.
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