Navigation Links
Scientists discover that host cell lipids facilitate bacterial movement

When the bacterium Listeria monocytogenes invades the body, it commandeers its host cell's actin cytoskeleton to invade other cells. In a report published in the Journal of Biological Chemistry, a group of scientists provide insight into the molecular mechanisms behind this infection technique.

The research appears as the "Paper of the Week" in the March 25 issue of the Journal of Biological Chemistry, an American Society for Biochemistry and Molecular Biology journal.

Listeria causes a variety of diseases, the most severe being meningoencephalitis, an inflammation of the brain and the membranes that envelop the brain and spinal cord. Infection begins when the bacterium binds to a receptor on the surface of a cell, causing the cell to ingest it. The bacterium multiplies inside the cell and then uses a cellular protein called ActA to stimulate the host cell's actin to form filaments at one end of the bacterium.

"As these filaments lengthen, they drive the bacterium through the cell until it reaches the peripheral or outer cell membrane," explains Dr. Frederick Southwick of the University of Florida College of Medicine. "Here the growing actin filaments push the bacterium against the membrane, forming long membrane projections called filopodia. These filopodia push into adjacent cells and are ingested by them. The bacteria then enter the new cell and begin the cycle anew. Essentially Listeria takes over or hijacks the host cell's actin cytoskeleton to move within cells, and to spread from cell to cell."

In most cells, two membrane lipids, PIP2 and PIP3, are associated with the formation of new actin filaments. PIP3 is synthesized from PIP2 by an enzyme called PI3-kinase. The lipids attract and modify the functions of proteins involved in regulating actin assembly. PIP2 and PIP3 also prevent capping proteins from binding to the ends of actin filaments, allowing new actin filament assembly.

Because Listeria is capable of stimulatin g actin assembly and PIP2 and PIP3 are known to localize to regions of new actin assembly, Dr. Southwick and his colleagues decided to explore the roles these lipids play in Listeria infection.

"We had expected to see PIP2 and PIP3 only at the very back of Listeria where new actin assembly was taking place," recalls Dr. Southwick. "To our surprise these lipids also localized to the front of the moving bacteria." The researchers also noticed that Listeria movement slowed down when the bacteria were treated with molecules that inhibited PI3-kinase, proving that Listeria depend on PI3-kinase to move.

"Our studies show that Listeria is capable of inside-out signaling," explains Dr. Southwick. "Most signals arise from molecules binding receptors on the outside of the cell. In the case of Listeria, we find that this intracellular pathogen can harness signals from the inner rather than the outer surface of the cell membrane.

"The most exciting and surprising finding is that an intracellular bacteria is able to attract host cell membrane lipids to its surface and these membrane lipids facilitate the ability of the bacterium to move within cells. This capability is unique to Listeria and is not found in another intracellular bacteria, Shigella. Our experiments show that Listeria is a simplified model system for studying how phosphoinositides regulate the actin cytoskeleton, and this model promises to yield additional insights into how these phospholipids control the cell's actin cytoskeleton. Our discoveries provide additional fundamental clues as how cells move."

These findings may also open the door to using PI3-kinase inhibitors or other agents that lower PIP2 and PIP3 levels to slow the spread of Listeria and control infection in patients who are not responding to antibiotics, although that application is a long way off, says Dr. Southwick.


'"/>

Source:American Society for Biochemistry and Molecular Biology


Related biology news :

1. Scientists ID molecular switch in liver that triggers harmful effects of saturated and trans fats
2. Scientists Replicate Hepatitis C Virus in Laboratory
3. Scientists detect probable genetic cause of some Parkinsons disease cases
4. Scientists find missing enzyme for tuberculosis iron scavenging pathway
5. Scientists seek answers on what activates deadly anthrax spores
6. Yale Scientists Find MicroRNA Regulates Ras Cancer Gene
7. Scientists collaborate to assess health of global environment
8. Scientists decipher genome of fungus that can cause life-threatening infections
9. Scientists discover the cellular roots of graying hair
10. Scientists rid stem cell culture of key animal cells
11. Scientists develop new color-coded test for protein folding
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:11/14/2016)... 14, 2016  xG Technology, Inc. ("xG" or the ... wireless communications for use in challenging operating environments, announced ... 2016. Management will hold a conference call to discuss ... Eastern Time (details below). Key Recent Accomplishments ... million binding agreement to acquire Vislink Communication Systems. The ...
(Date:6/22/2016)... LOS ANGELES , June 22, 2016 ... of identity management and verification solutions, has ... cutting edge software solutions for Visitor Management, ... ® provides products that add functional ... The partnership provides corporations and venues with ...
(Date:6/16/2016)... , June 16, 2016 ... is expected to reach USD 1.83 billion by ... View Research, Inc. Technological proliferation and increasing demand ... are expected to drive the market growth. ... The development of advanced multimodal techniques ...
Breaking Biology News(10 mins):
(Date:12/6/2016)... Dec. 6, 2016  SRI International has been ... from the National Institutes of Health,s National Institute ... of AIDS (NIAID-DAIDS) to support the manufacturing and ... (PreP) agents. Under the seven-year contract, SRI will ... services for candidate HIV-prevention products that emerge from ...
(Date:12/5/2016)... -- Axovant Sciences Ltd. (NYSE: AXON ), ... of dementia, today announced that data on the investigational ... will be presented at the 2016 Clinical Trials in ... in San Diego . Intepirdine presentations ... complex measures of activities of daily living (ADLs) and ...
(Date:12/5/2016)... ... December 05, 2016 , ... In anticipation of AxioMed’s exclusive ... production, company President, Jake Lubinski will be traveling to Germany on December 6th. ... Cologne and Karlsruhe to discuss the benefits of a viscoelastic total disc replacement. ...
(Date:12/5/2016)... , Dec. 5, 2016 NxGen MDx announced today that ... the test in house, we,ve been able to improve customer service through ... patients," says Alan Mack , CEO of NxGen MDx. ... , , A ... volume has led to more job opportunities at the Grand Rapid headquarters. ...
Breaking Biology Technology: