Bacteria Responsible for the Death of Most Patients with Cystic Fibrosis to Be Studied at UMass Amherst
March 14, 2008
| Contact: | Alejandro P. Heuck 413/545-0444 |
AMHERST, Mass. – Over 90 percent of patients with cystic fibrosis die from persistent lung infections caused by Pseudomonas aeruginosa, a bacterium that is resistant to many standard antibiotics. Alejandro P. Heuck of the University of Massachusetts Amherst has received an $80,000 grant from the American Lung Association to unlock the secrets of how this pathogen attacks cells.
“Mucus in the lungs of patients with cystic fibrosis becomes thick and dehydrated, leaving them vulnerable to chronic bacterial infections,” says Heuck, an assistant professor of biochemistry and molecular biology. “Pseudomonas aeruginosa is especially problematic since it takes up permanent residence in the lungs, and can never be completely eliminated. To make matters worse, only a few antibiotics are effective against it, and even the drugs we have are not effective against all strains.”
Pseudomonas aeruginosa is a common resident of soil and water and the ultimate opportunist, able to exploit any break in a host’s defenses. While never seen in healthy tissue, it can attack any tissue that is damaged, making it a common and deadly cause of infection in patients hospitalized for cancer, burns or cystic fibrosis. Pseudomonas aeruginosa also has a high tolerance for antibiotics, using antibiotic resistance genes and a thick membrane as defenses.
Heuck will try to outwit Pseudomonas aeruginosa by studying a small needle of proteins located on the surface of the bacterium, a structure that may have evolved from whip-like flagella used for locomotion. This needle-like apparatus is used during colonization and infection of cells, including cells of the lung and immune system. After attaching to target cells, the needle is used to open a channel in their cell membrane and inject toxins.
“If you can target the proteins at the tip of the needle and keep them from latching on to host cells and piercing their membranes, then you would have a way to stop the infection process,” says Heuck.
Since the proteins that make up the needle are identical to those found in similar structures in other bacteria, this research could be applicable to a host of diseases. “Pseudomonas aeruginosa, and many other pathogenic bacteria such as Yersinia, Salmonella, Shigella and Escherichia coli, employ a similar injection mechansim,” says Heuck. “Even though these bacteria inject different toxins, they all use the same type of needle tipped with the same proteins to attack cells.”
Heuck will use sophisticated laboratory techniques to determine how proteins in the tip of the needle recognize the target cells and form a three-dimensional structure capable of building a channel in their cell membranes. Knowing the structure of the proteins will allow for the design of new drugs that block the process.
“Antibiotics are usually molecules that can bind to proteins at specific sites and block their function,” says Heuck. “Our task is to identify and separate the proteins in the laboratory and tag them with markers to see which parts of the molecule are interacting with the membrane to form the transmembrane channel.”
Heuck is also using a toxin employed by the bacteria responsible for gas gangrene to create cellular probes that can measure the cholesterol content of cells. As a postdoctoral researcher at Texas A&M University, Heuck studied cholesterol-dependent toxins and participated in studies to determine how Staphylococcus epidermis, a bacterium that colonizes medical implants, binds to a protein in blood that is essential to the formation of clots.
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