Interfaculty Institute of Microbiology and Infection Medicine

RG Heilbronner

Research Focus

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 are able to expand and contract in an accordion-like fashion and create bacterial siblings with unique characteristics. 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.

We found that the GDA of a haem acquisition system in Staphylococcus lugdunensis transfers a competitive advantage to the lineage to thrive on haem as sole source of nutrient iron. This shows how GDAs can help to overcome selective pressures build up by our immune system. Similarly, GDAs are frequent in clinical isolates of the invasive pathogen Staphylococcus aureus and can create bacterial siblings with different immunostimulatory capacity. This shows that GDAs can impact host-pathogen interactions.

2) Competition for nutritional iron in microbial communities.

Iron is an essential trace element that needs to be acquired by all living organisms. Bacteria use small iron-binding siderophores to solubilize Fe-ions to increase biological availability. We find that harmless commensals consuming pathogen-derived siderophores can reduce the expansion of pathogens by limiting iron availability. These finding suggests that pathogens can be excluded from human microbiomes by introduction of siderophore consumers, a new strategy to prevent colonisation and infection by antibiotic resistant pathogens.

CV

Simon Heilbronner studied Biology with microbiology as major and immunology as minor subject in Tübingen (Germany) and Uppsala (Sweden). Having gained the Diploma he went to Ireland to work in the lab of Prof. Timothy J. Foster in Trinity College Dublin (TCD) where he earned his PhD-degree in 2014. Supported by an individual Marie Skłodowska-Curie fellowship he moved back to Germany. He is leading an independent research group in the department of Infection Biology since 2018.

 

Group members

Name/E-Mail Funktion
Simon Heilbronner Group Leader
Power, Jeffrey Postdoc
Lea Adolf Ph.D. student
Angelika Jochim Ph.D. student
Sharmila Sekar Ph.D. student
Detlinde Futter-Bryniok Technician
Darya Belikova Technician

Selected publications

Belikova D, Jochim A, Powers J, Holden MT, Heilbronner S. Gene accordions cause genotypic and phenotypic heterogeneity in clonal populations of Staphylococcus aureus. Nat Commun 11, 3526. https://doi.org/10.1038/s41467-020-17277-3 (2020)

Jochim A, Adolf L, Belikova D, Schilling NA, Setyawati I, Chin D, Meyers S, Verhamme P, Heinrichs DE, Slotboom DJ, Heilbronner S. An ECF-type transporter scavenges heme to overcome iron-limitation in Staphylococcus lugdunensis. Elife 9, doi:10.7554/eLife.57322 (2020).

Jochim A, Shi T, Belikova D, Schwarz S, Peschel A, Heilbronner S. Methionine Limitation Impairs Pathogen Expansion and Biofilm Formation Capacity. Appl Environ Microbiol 85, doi:10.1128/AEM.00177-19 (2019)

Heilbronner S. Commentary: Staphylococcus aureus Membrane-Derived Vesicles Promote Bacterial Virulence and Confer Protective Immunity in Murine Infection Models. Front Microbiol 9:2346 (2018).

Heilbronner S, Monk IR, Brozyna JR, Heinrichs DE, Skaar EP, Peschel A, Foster TJ. Competing for Iron: Duplication and Amplification of the isd Locus in Staphylococcus lugdunensis HKU09-01 Provides a Competitive Advantage to Overcome Nutritional Limitation. PLoS Genet, 12(8):e1006246 (2016).

Liesenborghs L, Peetermans M, Claes J, Veloso TR, Vandenbriele C, Criel M, Lox M, Peetermans WE, Heilbronner S, de Groot PG, Vanassche T, Hoylaerts MF, Verhamme P. Shear-Resistant Binding to von Willebrand Factor Allows Staphylococcus lugdunensis to Adhere to the Cardiac Valves and Initiate Endocarditis. J Infect Dis, 213(7):1148-1156 (2016).

Ernst CM, Kuhn S, Slavetinsky CJ, Krismer B, Heilbronner S, Gekeler C, Kraus D, Wagner S, Peschel A. The lipid-modifying multiple peptide resistance factor is an oligomer consisting of distinct interacting synthase and flippase subunits. MBio 6(1) (2015).

Heilbronner S, Hanses F, Monk IR, Speziale P, Foster TJ. Sortase A Promotes Virulence in Experimental Staphylococcus lugdunensis Endocarditis. Microbiology 159(Pt 10): 2141-2152 (2013).

Heilbronner, S., Monk, I. R., Foster, T. J. The phage integrase vector pIPI03 allows RecA-independent, site-specific labelling of Staphylococcus lugdunensis strains. Plasmid 70, 377-384, doi:10.1016/j.plasmid.2013.09.001 (2013)

Heilbronner S, Holden, MT, van Tonder A, Geoghegan, JA, Foster TJ, Parkhill J, Bentley SD. Genome sequence of Staphylococcus lugdunensis N920143 allows identification of putative colonization and virulence factors. FEMS Microbiol Lett 322, 60-67 (2011).


Funding