title: An Iron-Regulated Autolysin Remodels the Cell Wall To Facilitate Heme Acquisition in Staphylococcus lugdunensis.
abstract: Bacteria alter their cell surface in response to changing environments, including those encountered upon invasion of a host during infection. One alteration that occurs in several Gram-positive pathogens is the presentation of cell wall-anchored components of the iron-regulated surface determinant (Isd) system, which extracts heme from host hemoglobin to fulfill the bacterial requirement for iron. Staphylococcus lugdunensis, an opportunistic pathogen that causes infective endocarditis, encodes an Isd system. Unique among the known Isd systems, S. lugdunensis contains a gene encoding a putative autolysin located adjacent to the Isd operon. To elucidate the function of this putative autolysin, here named IsdP, we investigated its contribution to Isd protein localization and hemoglobin-dependent iron acquisition. S. lugdunensis IsdP was found to be iron regulated and cotranscribed with the Isd operon. IsdP is a specialized peptidoglycan hydrolase that cleaves the stem peptide and pentaglycine crossbridge of the cell wall and alters processing and anchoring of a major Isd system component, IsdC. Perturbation of IsdC localization due to isdP inactivation results in a hemoglobin utilization growth defect. These studies establish IsdP as an autolysin that functions in heme acquisition and describe a role for IsdP in cell wall reorganization to accommodate nutrient uptake systems during infection.
authors.affiliation: Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Allison J
authors.initials: AJ
authors.lastname: Farrand
authors.affiliation: Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Kathryn P
authors.initials: KP
authors.lastname: Haley
authors.affiliation: Department of Chemistry, Center for Innovative Technology, Institute of Chemical Biology, and Institute for Integrative Biosystems Research and Education, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: Nichole M
authors.initials: NM
authors.lastname: Lareau
authors.affiliation: Microbiology Department, Moyne Institute of Preventive Medicine, Trinity College, Dublin, Ireland.
authors.forename: Simon
authors.initials: S
authors.lastname: Heilbronner
authors.affiliation: Department of Chemistry, Center for Innovative Technology, Institute of Chemical Biology, and Institute for Integrative Biosystems Research and Education, Vanderbilt University, Nashville, Tennessee, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: McLean
authors.affiliation: Microbiology Department, Moyne Institute of Preventive Medicine, Trinity College, Dublin, Ireland.
authors.forename: Timothy
authors.initials: T
authors.lastname: Foster
authors.affiliation: Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA Tennessee Valley Healthcare Systems, U.S. Department of Veterans Affairs, Nashville, Tennessee, USA eric.skaar@vanderbilt.edu.
authors.forename: Eric P
authors.initials: EP
authors.lastname: Skaar
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism; D002473:Cell Wall / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D015151:Immunoblotting; D007501:Iron / Q000378:metabolism*; D013058:Mass Spectrometry; D009238:N-Acetylmuramoyl-L-alanine Amidase / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013203:Staphylococcal Infections / Q000378:metabolism*; D057787:Staphylococcus lugdunensis / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D007501:Iron; D009238:N-Acetylmuramoyl-L-alanine Amidase