How Bacterial Pathogens Â??sweeten’ Their Proteins Discovered in Colorado State Study

A Colorado State University study appearing in the August edition of Science Magazine reveals an unknown process of how bacteria are able to add sugars to proteins, a biochemical activity called protein glycosylation, which is linked to important biological functions in complex organisms ranging from yeast to man. The study will allow researchers to investigate how bacteria launch diseases in living organisms.

     The comprehensive study, conducted by researchers at the Mycobacteria Research Laboratories within the university’s Department of Microbiology, Immunology and Pathology, found that bacterium that causes tuberculosis, called Mycobacterium tuberculosis, and related bacteria use a process for protein glycosylation that is nearly identical to the process used in complex organisms.  

The research, conducted by a university team consisting of John Belisle, Brian VanderVen, Jeffery Harder and Dean Crick, showed that the tuberculosis-causing bacteria adds sugar to proteins using enzymes similar to those found in man and that this process occurs as the proteins are being exported to the outside of a bacterial cell.

"This study, along with other recent discoveries, demonstrates a previously unrealized evolutionary similarity between how bacteria and complex, or higher, organisms modify proteins by adding sugars as the proteins are exported outside of a cell or across membranes," said John Belisle, associate professor of microbiology, immunology and pathology. "The analogies we’ve pointed to in this research enables scientists to begin to establish a deeper understanding of how protein modification pathways are similar in what are otherwise very diverse biological systems."

Understanding how bacteria add sugars to proteins is a relatively new field of study. Scientists know that several disease-causing bacteria contain proteins on the surface of their cells that are modified with sugars. These proteins also influence interactions with the host of the bacteria, such as altering the host’s immune response to the bacterial infection.

"By understanding the mechanism by which bacteria modify proteins with sugars, the structure of these proteins and how these compare to similar systems in the infected host, it now becomes possible to study the influence of sugar-modified proteins, called glycoproteins, on the ability of bacteria to establish disease," said Karen Dobos, a microbiologist at Colorado State who was among the first scientists to describe protein glycosylation in the bacteria that causes tuberculosis.

In man and other animals, the addition of sugar to these biochemical activities allows protein to carry on specific tasks. For example, it alters protein folding, the process by which a linear combination of amino acids that form proteins take on a three-dimensional shape. A protein’s shape, which is impacted by its environment, determines its specific role as a building block in all living structures. Folded proteins fit together to form a number of larger systems such as enzymes, individual cells and configurations of cells, and chemicals critical for life. The process also influences cell signaling, or communicating between cells in living organisms.

The Colorado State University group intends to further define the role of protein glycosylation in M. tuberculosis and how such proteins influence the development of disease or are targeted by the immune response within the host organism.