title: Induction of Staphylococcus epidermidis biofilm formation via proteolytic processing of the accumulation-associated protein by staphylococcal and host proteases.
abstract: Because of its biofilm forming potential Staphylococcus epidermidis has evolved as a leading cause of device-related infections. The polysaccharide intercellular adhesin (PIA) is significantly involved in biofilm accumulation. However, infections because of PIA-negative strains are not uncommon, suggesting the existence of PIA-independent biofilm accumulation mechanisms. Here we found that biofilm formation in the clinically significant S. epidermidis 5179 depended on the expression of a truncated 140 kDa isoform of the 220 kDa accumulation-associated protein Aap. As expression of the truncated Aap isoform leads to biofilm formation in aap-negative S. epidermidis 1585, this domain mediates intercellular adhesion in a polysaccharide-independent manner. In contrast, expression of full-length Aap did not lead to a biofilm-positive phenotype. Obviously, to gain adhesive function, full-length Aap has to be proteolytically processed through staphylococcal proteases as demonstrated by inhibition of biofilm formation by alpha(2)-macroglobulin. Importantly, also exogenously added granulocyte proteases activated Aap, thereby inducing biofilm formation in S. epidermidis 5179 and four additional, independent clinical S. epidermidis strains. It is therefore reasonable to assume that in vivo effector mechanisms of the innate immunity can directly induce protein-dependent S. epidermidis cell aggregation and biofilm formation, thereby enabling the pathogen to evade clearance by phagocytes.
authors.affiliation: Institut für Infektionsmedizin, Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. rohde@uke.uni-hamburg.de
authors.forename: Holger
authors.initials: H
authors.lastname: Rohde
authors.forename: Christoph
authors.initials: C
authors.lastname: Burdelski
authors.forename: Katrin
authors.initials: K
authors.lastname: Bartscht
authors.forename: Muzaffar
authors.initials: M
authors.lastname: Hussain
authors.forename: Friedrich
authors.initials: F
authors.lastname: Buck
authors.forename: Matthias A
authors.initials: MA
authors.lastname: Horstkotte
authors.forename: Johannes K-M
authors.initials: JK
authors.lastname: Knobloch
authors.forename: Christine
authors.initials: C
authors.lastname: Heilmann
authors.forename: Mathias
authors.initials: M
authors.lastname: Herrmann
authors.forename: Dietrich
authors.initials: D
authors.lastname: Mack
mesh_terms: D018829:Adhesins, Bacterial / Q000096:biosynthesis / Q000378:metabolism; D001422:Bacterial Adhesion / Q000235:genetics / Q000502:physiology; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000378:metabolism*; D018441:Biofilms / Q000254:growth & development*; D006098:Granulocytes / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D008666:Metalloendopeptidases / Q000502:physiology*; D010447:Peptide Hydrolases / Q000502:physiology*; D013212:Staphylococcus epidermidis / Q000201:enzymology* / Q000502:physiology*; D000511:alpha-Macroglobulins / Q000378:metabolism
chemical_list: D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D000511:alpha-Macroglobulins; D010447:Peptide Hydrolases; D008666:Metalloendopeptidases; C022653:auR protein, Staphylococcus aureus