title: Competing for Iron: Duplication and Amplification of the isd Locus in Staphylococcus lugdunensis HKU09-01 Provides a Competitive Advantage to Overcome Nutritional Limitation.
abstract: Staphylococcus lugdunensis is a coagulase negative bacterial pathogen that is particularly associated with severe cases of infectious endocarditis. Unique amongst the coagulase-negative staphylococci, S. lugdunensis harbors an iron regulated surface determinant locus (isd). This locus facilitates the acquisition of heme as a source of nutrient iron during infection and allows iron limitation caused by "nutritional immunity" to be overcome. The isd locus is duplicated in S. lugdunensis HKU09-01 and we show here that the duplication is intrinsically unstable and undergoes accordion-like amplification and segregation leading to extensive isd copy number variation. Amplification of the locus increased the level of expression of Isd proteins and improved binding of hemoglobin to the cell surface of S. lugdunensis. Furthermore, Isd overexpression provided an advantage when strains were competing for a limited amount of hemoglobin as the sole source of iron. Gene duplications and amplifications (GDA) are events of fundamental importance for bacterial evolution and are frequently associated with antibiotic resistance in many species. As such, GDAs are regarded as evolutionary adaptions to novel selective pressures in hostile environments pointing towards a special importance of isd for S. lugdunensis. For the first time we show an example of a GDA that involves a virulence factor of a Gram-positive pathogen and link the GDA directly to a competitive advantage when the bacteria were struggling with selective pressures mimicking "nutritional immunity".
authors: Microbiology Department, Trinity College, Dublin, Ireland.|Infection Biology, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany.
authors: Simon
authors: S
authors: Heilbronner
authors: Microbiology Department, Trinity College, Dublin, Ireland.|Department of Microbiology and Immunology, University of Melbourne, Doherty Institute for Infection and Immunity, Parkville, Victoria, Australia.
authors: Ian R
authors: 0000-0001-6982-8074
authors: IR
authors: Monk
authors: Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada.
authors: Jeremy R
authors: JR
authors: Brozyna
authors: Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada.
authors: David E
authors: DE
authors: Heinrichs
authors: Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine and Tennessee Valley Healthcare Systems, US Department of Veterans Affairs, Nashville, Tennessee, United States of America.
authors: Eric P
authors: EP
authors: Skaar
authors: Infection Biology, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany.
authors: Andreas
authors: A
authors: Peschel
authors: Microbiology Department, Trinity College, Dublin, Ireland.
authors: Timothy J
authors: TJ
authors: Foster
mesh_terms: D056915:DNA Copy Number Variations / Q000235:genetics; D004697:Endocarditis, Bacterial / Q000235:genetics / Q000382:microbiology*; D020440:Gene Duplication; D056426:Genetic Loci / Q000235:genetics; D006418:Heme / Q000235:genetics / Q000378:metabolism; D006454:Hemoglobins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism*; D035925:Iron-Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D013203:Staphylococcal Infections / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D057787:Staphylococcus lugdunensis / Q000378:metabolism* / Q000472:pathogenicity; D013499:Surface Properties
chemical_list: D006454:Hemoglobins; D035925:Iron-Regulatory Proteins; D006418:Heme; D007501:Iron