Sharon Stahl,
takes pride in students' accomplishments
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Sharon Stahl, takes pride in students' accomplishments |
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H.
pylori's bacterial-host relationship
emphasized by study By Darrell Ward
The study suggests a dynamic and constantly evolving relationship between bacteria and host. Researchers found that stomach infections caused by the bacterium Helicobacter pylori lead first to mild inflammation. As the inflammation occurs, cells lining the stomach produce a specific kind of sugar molecule and display it on their surface. Normally, that sugar, known as sialyl-di-Lewis x (sLex), serves as a flag to attract immune cells to the infection site. The worse the inflammation, the more sLex the cells display. Investigators also discovered that H. pylori latches onto the new sugar using a previously unknown bacterial adhesin protein, enabling the bacteria to draw closer to the stomach cells, presumably where more nutrients are available. This worsens the inflammation and further increases the amount of sLex on the stomach cells. Some of the bacteria, which are loosely attached, may then move slightly away from the cells, avoiding destruction by immune cells that are attracted to the increasing display of sLex. The investigators believe that the degree of inflammation may then subside enough to allow those bacteria that closely move in again a good chance of surviving -- and profiting -- from the better nutrient supply. "These findings should improve our understanding of how H. pylori infection happens, how our immune system responds to it and how the bacteria cope with that response," said Douglas E. Berg, Ph.D., Alumni Professor in Molecular Microbiology and professor of genetics and co-author of the study. "We also hope that understanding how these adhesins work will lead to a vaccine against H. pylori infections and to new drugs to treat or diminish their severity." The findings also could help explain why the stomach inflammation that often accompanies the infection periodically flares up, then subsides, and why the infection persists for so long, said Berg, who also is a member of the tumor immunology program at the Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and the School of Medicine. "The ability of Helicobacter pylori to adjust its adherence properties to the level of inflammation it causes at the stomach surface could help explain how this bacterium maintains its persistent, decades-long infection in the stomach of millions worldwide," said lead investigator Thomas Borén, D.D.S., Ph.D., assistant professor of odontology and oral microbiology at Umeå University in Sweden. In 1993, Borén, working in collaboration with researchers at Washington University, learned that H. pylori used a molecule known as Lewis B antigen (Leb) to adhere to stomach cells. This study was followed up in 1998 when a collaborative effort by Borén's and the University's team identified the attachment protein used by the bacterium, calling it Lewis B antigen binding adhesin (BabA). Both findings also appeared in Science. The present study began with the intriguing observation that a mutant H. pylori strain engineered to lack BabA still adhered to highly inflamed stomach tissue from an H. pylori infected person, but could not adhere to healthy stomach tissue from an uninfected person. The bacterium, it seemed, had another adhesin, one that recognized a molecule associated with inflammation. Further study revealed that the bacteria were binding to sLex antigen, which is rare on healthy cells but present on inflamed cells. The investigators captured a fragment of the bacterial adhesin protein using a technique called receptor activity-directed affinity tagging, which they developed for the 1998 study. They then determined the amino-acid sequence of this fragment and used that to identify the gene encoding the protein. They called the new bacterial protein sialic-acid binding adhesin (SabA). The researchers then developed a strain of H. pylori that lacked the SabA gene and found that those bacteria were unable to adhere to inflamed stomach lining, confirming that SabA was responsible for the observation that triggered the study.
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