Scientists have discovered how the bacteria that causes Legionnaires’ disease digs in and makes a tiny shelter inside the cells of humans and other hosts.
The findings, published in Science, could offer insights into how other bacteria are able to survive inside cells, knowledge that could lead to new treatments for a wide variety of infections.
Discovered in 1976, Legionella, an aerobic gram-negative bacillus is responsible for Legionnaires’ disease, a condition of severe pneumonia. Spread through aerosolised water particles, it is a common cause of hospital and community-acquired pneumonia.
“Many infectious bacteria, from listeria to chlamydia to salmonella, use systems that allow them to dwell within their host’s cells,” explained study leader Vincent Tagliabracci, Ph.D., assistant professor of molecular biology at UTSW and member of the Harold C Simmons Comprehensive Cancer Center. “Better understanding the tools they use to make this happen is teaching us some interesting biochemistry and could eventually lead to new targets for therapy.”
Dr Tagliabracci’s lab studies atypical kinases, unusual forms of enzymes that put phosphates onto proteins or lipids, changing their function. Legionella is a particularly rich source of these noncanonical kinases. According to the Centers for Disease Control and Prevention, nearly 10 000 cases of Legionnaires’ disease were reported in the US in 2018, though the true incidence is believed to be higher.
After identifying a new Legionella atypical kinase named MavQ, Dr Tagliabracci and colleagues used a live-cell imaging technique in concert with a relatively new molecular tagging method to see where MavQ is found in infected human cells. However, rather than residing in a specific location, the researchers were surprised to see that the protein moved back and forth between the endoplasmic reticulum – a network of membranes important for protein and lipid synthesis – and bubble- or tube-shaped structures within the cell.
Further research suggests that MavQ, along with a partner molecule called SidP, remodels the endoplasmic reticulum so that Legionella can strip off sections of the membrane to help create and sustain the vacuole, a structure that the parasitic bacteria uses to shelter inside cells, protecting it from immune attack.
Dr Tagliabracci said that he suspects other bacterial pathogens may use similar mechanisms to co-opt existing host cell structures to create their own protective shelters.
Source: University of Texas
Journal information: Ting-Sung Hsieh, et al. Dynamic remodeling of host membranes by self-organizing bacterial effectors. Science, 2021; eaay8118 DOI: 10.1126/science.aay8118
