Pathogenic Gram-positive bacteria and vaccine development

Background

The factors we have focused on are the surface of the bacterial cell and soluble proteins that specifically interact with host components, such as extracellular matrix (ECM) or plasma proteins. These types of interactions are considered crucial steps for bacteria in the infection process.

The ability of these bacteria to cause disease in the host is generally thought to be complex due to several virulence factors, such as the expression of bacterial cell surface receptors (adhesins), capsule polysaccharides, toxins, and enzymes that can break down host components in combination with the host's condition. The adhesion of bacteria to components of the ECM at specific sites or structures in host cells and tissues is considered important in the infection process. This interaction depends on specific binding between the pathogen's adhesins and the host's ligands. The bacteria can also produce proteins that specifically interact with host components involved in the immune system and blood coagulation cascade, thereby, for example, avoiding phagocytosis and affecting the infected tissue. The relative importance of a particular interaction may vary depending on various factors, such as the site of infection or the type or stage of the disease. Many of these bacteria's extracellular proteins are multifunctional in their binding properties, which can be explained by their characteristic structure. They usually consist of different domains that may be repetitive. Therefore, the role of a single protein cannot be assessed by considering a selected individual binding property. It is therefore important to study these proteins at the molecular level and also extend the studies to cell and animal experiments.

For many years, our group has used molecular biology methods to study adhesins, or secreted proteins from pathogenic staphylococci and streptococci, which interact with various ECM and plasma proteins. The aim is to study the molecular mechanisms of the respective bacterium/host interactions and, through collaboration with other research groups, extend these studies to cell and animal experiments.

Aim

The purpose of the research is to study potential virulence factors in these bacteria and their interaction with hosts. 

Applied research

Although our scientific activities can be described as basic research, there is also an applied aspect, as there is a great need in society to develop new methods for combating pathogenic bacteria.

Over the years, we have been involved in several projects aimed at developing vaccines against pathogenic staphylococci and streptococci. In short, the goal of these projects was to develop vaccines to protect animals and humans against various diseases caused by pathogenic staphylococci and streptococci.

Below is a selection of our specific projects:

Studies of virulence factors in Streptococcus equi and Streptococcus zooepidemicus

For many years, we have studied Streptococcus equi subsp. equi (S. equi) and subsp. zooepidemicus (S. zooepidemicus). Both subspecies are associated with diseases in horses, with S. zooepidemicus being the most frequently isolated opportunistic pathogen causing infections in the respiratory tract, wounds, uterus, and reproductive disorders. Streptococcus zooepidemicus can be isolated from various animals and sometimes from humans, while S. equi is limited to horses and causes a serious and highly contagious respiratory disease called strangles.

In our studies, we have described various extracellular potential virulence factors in these subspecies and studied the interactions between these factors and hosts. Through collaboration with other research groups, we have also expanded our studies to include cell and animal experiments.

Vaccine against strangles

Since there was no safe and effective vaccine against strangles on the market, we started a collaborative project many years ago with the aim of developing a new safe and effective vaccine against strangles based on recombinant S. equi proteins. The results so far have been very promising, and the project has developed into a new company called Intervacc AB, which is in the process of launching the vaccine on the market.

Examples of vaccination and provocation experiments on horses with a combination of different recombinant S. equi proteins (Septavacc). Modified from Guss et al 2009 PLoS Pathog.