In the late 1600s, Antonie van Leeuwenhoek, the “father of microbiology,” peered into a microscope and noticed an unusual thread-like oral spirochete, a type of free-living bacterium, that would later receive the name Treponema denticola. More than 300 years later, this thread-like spirochete remains very much under the research microscope.
T denticola is a member of the so-called red microbial complex, a triad of oral pathogens that are strongly associated with the most severe and chronic forms of periodontitis. Studies show that T denticola normally comprises less than 1% of the mouth’s total bacterial load. But in the periodontal pockets, the bacterium can exceed 40% of the microbial population. In the June 2011 issue of the journal Acta Crystallographica Section F Structural Biology Crystallography Communications, National Institute of Dental and Craniofacial Research (NIDCR) grantees and colleagues have placed T denticola under the microscope again, obtaining recombinant crystals to begin the process of solving the 3-dimensional crystal structure of its factor H-binding protein B (FhbB). The 11.4-kDa, 102-amino-acid surface protein plays a critical role in helping the bacterium survive in gingival crevices and periodontal pockets. The human body produces approximately 30 different proteins that are collectively referred to as complement. Complement recognizes pathogens and tags them for killing by other components of the innate immune system, our inherited first line of defense against pathogens. However, too much complement activity can damage our own cells. To solve this problem, the innate immune system relies on several proteins—including a glycoprotein called factor H (FH)—to negatively regulate complement activity.
Enter the FhbB protein of T denticola. Mounted on the bacterium’s surface like a biochemical magnet, FhbB attracts circulating FH and exploits its negative regulatory ability as biochemical cover to evade the complement system. This allows T denticola to survive and thrive in periodontal pockets. Interestingly, FhbB is the smallest known bacterial protein that binds FH. With its crystal structure in hand, the authors say they can begin to parse the protein to define the minimum molecular requirements, or signature, required to bind FH. This fundamental information will facilitate the development of therapeutic and preventive approaches for periodontal disease and other important infectious diseases. In addition, the study of the FH-FhbB interaction will also provide unique insight into several inheritable diseases that are attributed to aberrant FH activity including age-related macular degenerative disease and atypical hemolytic uremic syndrome.
(Source: NIDCR Science News in Brief, August 11, 2011)
