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Team makes bacteria breakthrough

Better control of cross contamination in hospitals may be available within the next four to five years after a group of researchers yesterday touted success in discovering a new way to apply thrombomodulin, a natural anticoagulant that helps to prevent and curtail inflammatory responses caused by bacteria.

The breakthrough, which could potentially replace the use of antibiotics in infection prevention and treatment, was published in the journal Blood on Aug. 18.

During the National Science Council (NSC) sponsored project, Wu Hua-lin (吳華林), a professor at the National Cheng-Kung University College of Medicine’s Department of Biochemistry and Molecular Biology, found that thrombomodulin, in addition to helping prevent blood coagulate, can also help the body fight gram-negative bacterial infection.

“Gram-negative bacteria, including E. coli and Klebsiella pneumoniae, account for a large proportion of infections in hospitals,” Wu said.

Traditionally, patients are put on antibiotics to prevent cross-contamination. However, because of the development of resistance to antibiotics, doctors often end up battling bacteria by administering higher doses of drugs or experimenting with different types of antibiotics.

Wu found that while the thrombomodulin molecule can be divided into five domains, “The first, which is a lectin-like domain, is able to bind with the lipopolysaccharide [LPS, an endotoxin that is a compound of fat and multiple sugars] on the gram-negative bacteria outer surface, and cause the bacteria to group,” he said.

“When enough bacteria are grouped, they invite macrophage molecules in the immune system to engulf them,” he said.

“The effect is two-fold – not only does thrombomodulin enhance bacteria clearance in circulation, it prevents LPS-induced inflammation,” Wu said.

The inflammation prevention mechanism would be the third new function Wu has discovered in thrombomodulin, as he found that the molecule played a role in cell-cell adhesion in 2003, which retards tumor growth, and angiogenisis [blood vessel growth] in 2005, he said.

“Cells have to have good contact with one another … If a tumor grows in an area of the body that suffers from loss of cell-cell adhesion, its [the tumor’s] cell proliferation is expedited,” Wu said.

In other words, since thrombomodulin aids cells in adhering to each other, it can slow tumor growth, he said.

With the latest breakthrough, Wu’s team is looking to bioengineer the molecules to make therapeutic drugs, Wu said.

He added that so far successful trials, showing that thrombomodulin is effective in clearing LPS and Klebsiella pneumonia, have been completed in mice.

“Inflammation or deaths caused by the bacteria are also reduced,” he said.

“Since thrombomodulin is a protein, it would be relatively simple to synthesize … With clinical trials and drug certification, we are looking at four to five years before the new therapy can reach the market,” Wu said.
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