Interfaculty Institute of Microbiology and Infection Medicine

Forschungsschwerpunkte


1) Gene amplification causes prokaryotic heterogeneity.

Gene duplication and amplification (GDA) is a RecA-dependent genetic process allowing the creation of gene arrays (identical copies of genes in a repeated fashion). These arrays can expand and contract in an accordion-like fashion and create bacterial siblings with unique characteristics due to gene doses-effects. Little is known about the frequency of duplications in clinical populations of pathogens and the importance of the mechanism to influence the success of a lineage during colonization or during invasive disease is unclear. Using long read and short read genome sequencing approaches, we found GDAs to be frequent in clinical isolates of the invasive pathogen Staphylococcus aureus. In vitro and in vivo, GDAs occurred rapidly in various chromosomal regions and created bacterial siblings with different phenotypes. Exemplarily GDAs altered the immunostimulatory capacity of lineages, giving a first example that GDAs can impact host-pathogen interactions. Similarly, we found that the GDA of a heme acquisition system in Staphylococcus lugdunensis transfers a competitive advantage to the lineage to thrive on heme as sole source of nutrient iron, showing that GDAs can help to overcome selective pressures built up by our immune system.

 

2) Acquisition of and competition for trace nutrients in bacterial communities.

Bacterial pathogens are frequently hiding in human microbiomes and cause significant morbidity and mortality when they succeed in causing infection. Preventing pathogen colonisation by targeted microbiome intervention (e.g. by introduction of probiotic commensals) is a promising strategy to reduce the microbiome-associated risks of infection. However, we need to understand the central interactions between human pathogens and commensals to identify the most promising strains and species for pathogen displacement. Competition for scarce nutrients is most likely of central importance under the nutritionally poor conditions on human body surfaces and my lab studies two aspects of bacterial acquisition of and competition for nutrients.

     a) Mechanisms of trace element acquisition and physiological effects of their limitation
Iron is an essential trace element that needs to be acquired by all living organisms. My lab recently discovered a novel strategy for the acquisition of heme-iron by Staphylococcus lugdunensis. The mechanism is unique as it employs a membrane-embedded transporter of the Energy-Coupling Factor type which is generally associated with vitamin acquisition but has never been associated with iron-acquisition. Additionally, my lab investigates the physiological effects of nutrient starvation on bacterial pathogens. We found that blockage of the methionine biosynthesis pathway severely impacts bacterial growth as well as biofilm formation. This suggest that the pathway represents an attractive target for antibacterial compounds in the nutrient-limited environment of the human body.

     b) Competition for iron binding-siderophores fosters competition among members of the nasal microbiome.
Bacteria use small iron-binding siderophores to solubilize Fe-ions to increase biological availability. However, siderophores are costly to produce and represent public goods that are available to all members of the community upon secretion. In unpublished experiments we found that siderophore production is crucial for the pathogen S. aureus to colonize the anterior nares of experimental animals. Interestingly, we found plentiful siderophore-based interactions between S. aureus and nasal commensals. Some commensals produced siderophores supporting S. aureus proliferation, while others consumed S. aureus-derived siderophores which reduced pathogen expansion. These findings suggest that S. aureus might be excluded from human microbiomes by introduction of siderophore consumers, a new strategy to prevent colonisation to reduce infection.

The combined approaches of my laboratory aim to understand the collaborative and competitive interactions between human commensals and pathogens to facilitate the design of pathogen exclusion strategies.