Projects

Bacterial outer membrane proteins and adhesion
Adherence to epithelial cells lining the mucosal tract, or to the extracellular matrix is essential for the initiation of infection and thus facilitates pathogens to entry into the host tissue. The interactions between pathogens and the host are well known to be multifactorial, involving combinations of protein-carbohydrate and protein-protein interactions, or mediated by bridging molecules recognizing ligands on both the host and pathogens. We have identified several proteins with different adhesive properties from both H. influenzae and M. catarrhalis. For example, protein E, a well-conserved multifunctional protein of non-typeable H. influenzae (NTHi), binds to vitronectin, plasminogen and laminin. H. influenzae can efficiently attach and activate epithelial cells when protein E is expressed on the bacterial cell membrane. We are currently also studying adhesive properties and proteins of Pseudomonas aeruginosa and are mapping the interactome for vitronectin and laminin. In addition, we are studying the bacterial adaptation skills to different anatomical sites.

Pathogens use different strategies to avoid the innate immune system
When microbes enter the human body they face an arsenal of different molecules working together to eradicate foreign objects. Most bacterial species have therefore evolved several strategies to avoid and block these mechanisms. We have identified many different interactions with complement regulatory proteins (inhibitors) contributing to serum resistance of the respiratory pathogens. Several Haemophilus proteins contribute to serum resistance through binding of vitronectin, that is, Hsf in encapsulated H. influenzae type b and Protein E and Protein F in non-typeable H. influenzae (NTHi). Both H. influenzae and M. catarrhalis thus interfere with the classical, alternative and finally the terminal pathways of the complement system via its respective regulators C4BP, Factor H and vitronectin. Interestingly, each interaction contributes to increased serum survival of the pathogens. Even though Moraxella and NTHi seldom cause invasive infections, the described mechanisms are important for bacterial survival also in the respiratory tract since plasma components are involved in the mucosal immunity.

Membrane vesicles and antibiotic resistance
In recent years it has become more and more evident that antimicrobial resistance is an increasingly serious threat to global public health. According to the ECDC (European Centre for Disease Prevention and Control), more than 25,000 patients die from infections due to antibiotic resistant bacteria in the European Union every year. M. catarrhalis is one pathogen that the last two decades has gained resistance against beta-lactamase based antibiotics and today more than 97 % of all M. catarrhalis strains are resistant. M. catarrhalis produces outer membrane vesicles (OMV), small spheres consisting of lipids, protein and DNA. Interestingly, we recently demonstrated that OMV carry the beta-lactamase and hereby protect susceptible bacteria against killing. We are currently in detail studying the role of OMV regarding Moraxella antibiotic resistance and its importance for interactions with other pathogens dwelling in the respiratory tract.

Epidemiology of H. influenzae in Sweden
Since the introduction of a conjugated vaccine directed against H. influenzae type b (Hib) in the early 1990s, Hib infections have successfully been eliminated. However, we have recently shown an increase of invasive disease due to non-type b strains, such as NTHi (non-typeable H. influenzae) and serotype f (Hif). In a recent study we also showed an increased incidence of betalactam resistant invasive H. influenzae and that these in parts are clonal, that is, originating from the same predecessor.

Helicobacter pylori
One third of the world’s population carries the bacterial species Helicobacter pylori that causes ulcers in a large numbers of patients. A long-term infection with Helicobacter can also lead to gastric cancer. Gastric cancer is the fifth most common cancer in the world with, unfortunately, a relatively high mortality. Infection with Helicobacter may also be related to the development of MALT lymphoma, a cancer that originates from B lymphocytes. Today Helicobacter infections are treated with antibiotics, but with an ongoing development of resistance the development of innovative therapies are required. We are studying the interaction of Helicobacter with human proteins, and have recently focused on the binding of vitronectin and identified the bacterial counterpart. The interaction contributes to an increased survival from complement-mediated attacks, which indicates that it plays an important role for the bacterial persistance in human tissue.