Scientists at UT Southwestern have discovered a key protein that helps the bacteria responsible for Legionnaire’s disease get into the cells of humans and other hosts. The results, published in Science, could offer information on how other bacteria are able to survive inside cells, knowledge that could lead to new treatments for a wide variety of infections.
“Many infectious bacteria, from listeria to chlamydia to salmonella, use systems that allow them to live in the cells of their host”, explains study leader Vincent Tagliabracci, Ph.D., professor assistant in molecular biology at UTSW and member of the Harold C. Simmons Comprehensive Cancer Center. “Better understanding the tools they use to achieve this teaches us interesting biochemistry and could potentially lead to new therapeutic targets.”
Tagliabracci’s lab studies atypical kinases, unusual forms of enzymes that transfer chemical groups called phosphates to proteins or lipids, altering their function. Research here and elsewhere has shown that Legionella, the genus of bacteria responsible for Legionnaires’ disease, is a particularly rich source of these non-canonical kinases. According to the Centers for Disease Control and Prevention, nearly 10,000 cases of Legionellosis were reported in the United States in 2018, although the actual incidence is believed to be higher.
After identifying a new atypical Legionella kinase named MavQ, Tagliabracci and his colleagues used a live cell imaging technique combined with a relatively new molecular labeling method to see where MavQ is found in infected human cells, a clue of his function. Rather than residing in a specific location, the researchers were surprised to see that the protein oscillated between the endoplasmic reticulum – a network of membranes important for protein and lipid synthesis – and the bubble or tube-like structures within the cell. .
Further research suggests that MavQ, along with a partner molecule called SidP, reshapes the endoplasmic reticulum so that Legionella can steal parts of the membrane to help create and maintain the vacuole, a structure that houses the parasite inside them. cells and protects it from immune attacks.
Tagliabracci, a Michael L. Rosenberg medical research fellow and a researcher at the Texas Institute for Cancer Research and Prevention (CPRIT), says he suspects other bacterial pathogens could use similar mechanisms to co-opt the structures of existing host cells in order to create their own protective dwellings. .
This work was funded by NIH Grants DP2GM137419, R01GM113079, T32GM008203-29, F30HL143859-01, Welch Foundation Grants I-1911, I-1789, CPRIT Grant RP170674, and Polish National Agency Fellowship for scientific exchanges PPN / BEK / 2018/1 / 00431.
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