Induction of Staphylococcus epidermidis biofilm formation via proteolytic processing of the accumulation-associated protein by staphylococcal and host proteases.
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.
Rohde
Holger
H
Institut für Infektionsmedizin, Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. rohde@uke.uni-hamburg.de
Burdelski
Christoph
C
Bartscht
Katrin
K
Hussain
Muzaffar
M
Buck
Friedrich
F
Horstkotte
Matthias A
MA
Knobloch
Johannes K-M
JK
Heilmann
Christine
C
Herrmann
Mathias
M
Mack
Dietrich
D
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
D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D000511:alpha-Macroglobulins; D010447:Peptide Hydrolases; D008666:Metalloendopeptidases; C022653:auR protein, Staphylococcus aureus