title: Molecular determinants of staphylococcal biofilm dispersal and structuring.
abstract: Staphylococci are frequently implicated in human infections, and continue to pose a therapeutic dilemma due to their ability to form deeply seated microbial communities, known as biofilms, on the surfaces of implanted medical devices and host tissues. Biofilm development has been proposed to occur in three stages: (1) attachment, (2) proliferation/structuring, and (3) detachment/dispersal. Although research within the last several decades has implicated multiple molecules in the roles as effectors of staphylococcal biofilm proliferation/structuring and detachment/dispersal, to date, only phenol soluble modulins (PSMs) have been consistently demonstrated to serve in this role under both in vitro and in vivo settings. PSMs are regulated directly through a density-dependent manner by the accessory gene regulator (Agr) system. They disrupt the non-covalent forces holding the biofilm extracellular matrix together, which is necessary for the formation of channels, a process essential for the delivery of nutrients to deeper biofilm layers, and for dispersal/dissemination of clusters of biofilm to distal organs in acute infection. Given their relevance in both acute and chronic biofilm-associated infections, the Agr system and the psm genes hold promise as potential therapeutic targets.
authors.affiliation: Pathogen Molecular Genetics Section, Laboratory of Human Bacterial Pathogenesis, National Institute of Allergy and Infectious Diseases, National Institutes of Health Bethesda, MD, USA ; Division of Hospital Internal Medicine, Department of Medicine, Mayo Clinic College of Medicine Rochester, MN, USA.
authors.forename: Katherine Y
authors.initials: KY
authors.lastname: Le
authors.affiliation: Pathogen Molecular Genetics Section, Laboratory of Human Bacterial Pathogenesis, National Institute of Allergy and Infectious Diseases, National Institutes of Health Bethesda, MD, USA ; Department of Orthopedic Surgery, Thomas Jefferson University School of Medicine Philadelphia, PA, USA.
authors.forename: Sana
authors.initials: S
authors.lastname: Dastgheyb
authors.affiliation: Pathogen Molecular Genetics Section, Laboratory of Human Bacterial Pathogenesis, National Institute of Allergy and Infectious Diseases, National Institutes of Health Bethesda, MD, USA ; Uniformed Services University of the Health and Sciences, School of Medicine Bethesda, MD, USA.
authors.forename: Trung V
authors.initials: TV
authors.lastname: Ho
authors.affiliation: Pathogen Molecular Genetics Section, Laboratory of Human Bacterial Pathogenesis, National Institute of Allergy and Infectious Diseases, National Institutes of Health Bethesda, MD, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Otto
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D018441:Biofilms; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D013203:Staphylococcal Infections / Q000382:microbiology*; D013210:Staphylococcus / Q000235:genetics / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism
chemical_list: C095698:Agr protein, Staphylococcus aureus; D001426:Bacterial Proteins; D015534:Trans-Activators
keywords: Staphylococcus aureus; Staphylococcus epidermidis; biofilm; medical devices; phenol-soluble modulins