Gene duplication and amplification (GDA) describes 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. GDAs are frequently associated with unusual resistances against antibiotics. However 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. Furthermore, we found that GDAs are frequent in clinical populations of Staphylococcus aureus, affecting especially genic loci encoding lipoproteins. GDAs of this locus leads to phenotypic switching and the impacts on colonization and disease are under current investigation.
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 2013. Supported by an individual Marie Skłodowska-Curie fellowship he moved back to Germany where he now establishes his research group focusing on gene duplication and amplifications in staphylococci and their influence on infectivity and virulence.
- 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).
- Farrand AJ, Haley KP, Lareau NM, Heilbronner S, McLean JA, Foster T, Skaar EP: An Iron-Regulated Autolysin Remodels the Cell Wall To Facilitate Heme Acquisition in Staphylococcus lugdunensis. Infect Immun, 83(9):3578-3589 (2015).
- Missineo A, Di Poto A, Geoghegan JA, Rindi S, Heilbronner S, Gianotti, V, Arciola CR, Foster TJ, Speziale P, Pietrocola G: IsdC from Staphylococcus lugdunensis Induces Biofilm Formation under Low-Iron Growth Conditions." Infect Immun 82(6): 2448-2459 (2014).
- Heilbronner S, Monk IR, Foster TJ: The phage integrase vector pIPI03 allows RecA-independent, site-specific labelling of Staphylococcus lugdunensis strains. Plasmid 70(3): 377-384 (2013).
- 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, 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).
Irish Research Council (IRCSET 'Embark Initiative') – Investigation of Staphylococcus lugdunensis; genome sequence and beyond.
German Academic Exchange (DAAD) – Duplication and Amplification of the isd operon in Staphylococcus lugdunensis.
European Commission for Research and Innovation – Gen Duplication and Amplification in Staphylococcal Populations. Individual Marie Skłodowska -Curie fellowship (2015-2017)
Ministerium für Wissenschaft, Forschung und Kunst Baden-Württemberg - RiSC-Program - Detection and Effects Of Gene Amplification In Staphylococcal Clonal Populations (2018-2019)