Funding: DFG (HE 3546/6-1) (1/2018 bis 12/2022)
The importance of post-translational protein glycosylation in the pathogenesis of S. aureus infections is not well understood yet. In this project, we further analyze the importance of glycosylation of S. aureus surface proteins, such as PIs in biofilm formation and tissue colonization.
Funding: IZKF Münster Hei2/027/18 (01/2018 bis 12/2020)
Extracellular (e)DNA is a major structural component of staphylococcal biofilms. We identified a novel mechanism of eDNA generation in the coagulase-negative Staphylococcus lugdunensis mediated by the competence gene comEB. comEB is part of the comEABC competence operon. The S. lugdunensis comEB mutant has a severe defect in biofilm formation with strongly decreased eDNA levels as visualized by confocal laser scanning microscopy (see Figure). The underlying mechanisms in the eDNA-dependent biofilm formation mediated by the competence operon comEABC were studied in more detail.
Funding: IZKF Münster Hei2/027/14 (01/2014 bis 10/2017)
Most bacterial glycoproteins identified to date are virulence factors of pathogenic bacteria. The importance of protein glycosylation in the pathogenesis of S. aureus infections remains largely unknown. We identified the plasmin-sensitive protein PIs from S. aureus as a glycoprotein and found that the glycosyltransferases GtfC/GtfD and GtfE/GtfF are involved in its glycosylation. The role of PIs glycosylation in different aspects of S. aureus pathogenicity was studied in more detail.
Funding: DFG (HE 3546/2-2) (06/2013 bis 03/2017)
In this prolongation project, we characterized the previously identified Atl-mediated staphylococcal internalization mechanism by human host cells in detail (see Figure).
Funding: DFG (HE 3546/3-1) (07/2007 bis 10/2011)
Interaction between staphylococci and Candida yeasts can occur either directly or mediated by bridging molecules, such as the extracellular matrix and plasma proteins fibrinogen and fibronectin, as suggested by adhesion and coaggregation assays. To identify staphylococcal factors involved in this interaction, we used the phage display technique. We identified domains of the S. aureus extracellular fibrinogen-binding proteins coagulase and Efb binding to Candida biofilms. The coagulase leads to the conversion of fibrinogen to fibrin, which may shield the Candida cells against the host immune defense as suggested by CLSM (see Figure). Indeed, phagocytosis assays demonstrated a reduced phagocytosis rate of Candida in the presence of coagulase or Efb. The inhibition of phagocytosis of Candida cells by coagulase and Efb via two distinct mechanisms suggests that S. aureus might be beneficial for Candida to persist as it helps Candida to circumvent the host immune system.
Funding: IZKF Münster Hei2/022/09 (01/2009 bis 10/2012)
Staphylococci are serious pathogens that can cause implant-associated infections leading to significant morbidity and mortality. Colonization of the implanted medical devices by the formation of a three-dimensional structure made of bacteria and host material called biofilm is considered the most critical factor in these infections. In this project, we identified and characterized the 238 kDa S. aureus surface protein C (SasC) that mediated the formation of huge cell aggregates indicative of intercellular adhesion, higher attachment to polystyrene, and enhanced biofilm formation to S. carnosus and S. aureus. We localized the domain conferring these traits in the N-terminal protein domain. The SasC-mediated cell aggregation and biofilm formation of S. aureus may play an important role in colonization during infection with this important pathogen.
Funding: DFG (HE 3546/2-1) (01/2006 bis 12/2008)
Staphylococcus aureus is a serious pathogen that causes life-threatening chronic and recurrent infections due to its ability to persist inside the host cells. Thus, the pathogens capability to adhere to host tissue and to be internalized by human host cells are considered as critical pathogenicity factors in these infections leading to escape from the host immune response and from antibiotic therapy. The main mechanism of S. aureus internalization is thought to depend on the fibronectin-binding proteins (FnBPs). In this project, we described a novel mechanism of staphylococcal internalization that involves the major autolysin/adhesin Atl and AtlE from S. aureus and S. epidermidis, respectively. Moreover, we identified the human heat shock cognate protein Hsc70 as putative host cell receptor in Atl-mediated uptake of staphylococcal cells. While this novel mechanism of internalization may represent a “backup”-mechanism in S. aureus internalization, it may represent the major or even sole mechanism involved in internalization of coagulase-negative staphylococci and therefore may play an important role in the pathogenesis of chronic and recurrent bone diseases caused by S. epidermidis.
Funding: DFG (GRK 1409: The International Graduate School: "Molecular interactions of pathogens with biotic and abiotic surfaces" (10/2006 bis 09/2016)
S. epidermidis and S. aureus belong to the most important pathogens causing life-threatening infections, such as endocarditis and sepsis, which may be foreign-body associated. The ability of the staphylococci to form a biofilm is considered the most critical pathogenicity factor involved. Biofilm formation is a two-step process: First, the bacteria attach to a biotic or abiotic surface. Then, the bacteria proliferate and accumulate into multilayered biofilms. After biofilm maturation, single cells or small agglomerates of staphylococci can detach from the biofilm and hematogeneously seed to different organs to start an infection at a different site, e.g. infective endocarditis. In this long-term project, we studied different aspects of staphylococcal biofilm formation in detail.
Funding: IZKF Münster Hei2/042/04 (01/2004 bis 10/2007)
Förderung: DFG-Projekt im SFB 293, Teilprojekt A6 (1/2003 bis 12/2008)
Förderung: Medizinische Fakultät der Universität Münster: "Innovative Medizinische Forschung (IMF)" (2000-2001)
