Structure and function of bacterial virulence factors
A bacterial biofilm is a complex network of bacteria and host tissue. We are using protein X-ray crystallography to study its molecular components in detail.
Our research is mainly directed towards understanding bacteria-bacteria and bacteria-host interactions, with the long term goal to shed light on biofilm formation and infection mechanisms. The first step towards understanding these molecular interactions is to study the structure and function of bacterial surface molecules that are involved. Investigating the structures of these surface proteins at an atomic level is the first step towards the possibility to interfere with certain interactions to hinder attachment and infection. The main technique that we are using is protein X-ray crystallography.
In addition, we are involved in several other projects where structure biology is one of the main techniques to answer biological questions.
Some of the projects:
1. Surface adhesins expressed by oral streptococci. Streptococci are among the first colonizers of the oral cavity when the oral biofilm (dental plaque) is formed. The composition of the oral streptococci is the first step towards determining whether the biofilm will exist in commensal harmony with the host of if pathogens will proliferate and cause caries and periodontitis. One of the surface adhesins that is commonly found on oral streptococci, and important for the formation of the oral biofilm, that is antigen I/II (AgI/II). AgI/II is a very large protein and we have solved several crystal structures of domains from both Streptococcus gordonii and Streptococcus mutans AgI/II. AgI/II is also expressed on Streptococcus pyogenes, and we have solved structures of the S. pyogenes protein for comparison.
2. Porphyromonas gingivalis proteins. P. gingivalis is a Gram-negative late colonizer that is the main cause of adult periodontitis. P. gingivalis known to hide from the human immune system and to be involved in the onset of systemic diseases such as cardiovascular disease and cancer. We are studying its surface molecules in order to understand how this bacterium can attach to the oral biofilm and to host cells.
3. Transportation of lipidated proteins. Gram-negative bacteria have several systems to transport proteins between the inner and outer membrane. One pathway is based on the transport of lipidated proteins (the Lol-system). The proteins are lipidated at the inner membrane and recognized by the membrane protein complex LolCDE. The lipidated protein is next transferred to the soluble protein LolA that transfers it to the outer membrane where LolB receives it. We are studying the structure and function of LolA, LolB and the LolCDE complex.
4. Actinomyces oris proteins. A. oris is, as the oral streptococci, among the first colonizers of the oral biofilm. A. oris expresses two forms of pili, type-1 and type-2. We have solved the crystal structures of the main component the type-1 pili (FimP) as well as the enzyme, the sortase, that is needed to polymerize the subunits into mature pili. We are also interested in its disulfide forming mechanism, necessary to correctly fold pili proteins and other virulence factors.
5. Cyanobacteria. Cyanobacteria are photosynthetic bacteria interesting for both the production of biomass and biofuel. In collaboration with Christiane Funk (Umeå University) and Karin Stensjö (Uppsala University) are we studying the structure and function of several key enzymes.
6. Cytotoxins. Vibrio cholerae produces a tripartite cytotoxin, MakABE that is secreted via the bacterial flagellum. We are studying the structure and function of these proteins. We have solved the crystal structures of the soluble forms of MakA, MakB and MakE using X-ray crystallography. The membrane bound forms will be studied using electron microscopy. In collaboration with Aftab Nadeem, Sun Nyunt Wai and Bernt Eric Uhlin (Umeå University).
Deepika Jaiman, Dr. Karin Ernits and Dr. Nandita Bodra
Previous group members:
Nina Forsgren (PhD 2010), Åsa Nylander (PhD 2013), Patrik Kloppsteck, (postdoc), Michael Hall (postdoc), Thomas Heidler (postdoc), Raghavendra Nagampalli (postdoc)