The metalloprotease SepA governs processing of accumulation-associated protein and shapes intercellular adhesive surface properties in Staphylococcus epidermidis

TY - JOUR

T1 - The metalloprotease SepA governs processing of accumulation-associated protein and shapes intercellular adhesive surface properties in Staphylococcus epidermidis

AU - Paharik, Alexandra E

AU - Kotasinska, Marta

AU - Both, Anna

AU - Hoang, Tra-My

AU - Büttner, Henning

AU - Roy, Paroma

AU - Fey, Paul D

AU - Horswill, Alexander R

AU - Rohde, Holger

N1 - © 2016 John Wiley & Sons Ltd.

PY - 2017/3

Y1 - 2017/3

N2 - The otherwise harmless skin inhabitant Staphylococcus epidermidis is a major cause of healthcare-associated medical device infections. The species' selective pathogenic potential depends on its production of surface adherent biofilms. Cell wall-anchored protein Aap promotes biofilm formation in S. epidermidis, independently from the polysaccharide intercellular adhesin PIA. Aap requires proteolytic cleavage to act as an intercellular adhesin. Whether and which staphylococcal proteases account for Aap processing is yet unknown. Here, evidence is provided that in PIA-negative S. epidermidis 1457Δica, the metalloprotease SepA is required for Aap-dependent S. epidermidis biofilm formation in static and dynamic biofilm models. qRT-PCR and protease activity assays demonstrated that under standard growth conditions, sepA is repressed by the global regulator SarA. Inactivation of sarA increased SepA production, and in turn augmented biofilm formation. Genetic and biochemical analyses demonstrated that SepA-related induction of biofilm accumulation resulted from enhanced Aap processing. Studies using recombinant proteins demonstrated that SepA is able to cleave the A domain of Aap at residue 335 and between the A and B domains at residue 601. This study identifies the mechanism behind Aap-mediated biofilm maturation, and also demonstrates a novel role for a secreted staphylococcal protease as a requirement for the development of a biofilm. This article is protected by copyright. All rights reserved.

AB - The otherwise harmless skin inhabitant Staphylococcus epidermidis is a major cause of healthcare-associated medical device infections. The species' selective pathogenic potential depends on its production of surface adherent biofilms. Cell wall-anchored protein Aap promotes biofilm formation in S. epidermidis, independently from the polysaccharide intercellular adhesin PIA. Aap requires proteolytic cleavage to act as an intercellular adhesin. Whether and which staphylococcal proteases account for Aap processing is yet unknown. Here, evidence is provided that in PIA-negative S. epidermidis 1457Δica, the metalloprotease SepA is required for Aap-dependent S. epidermidis biofilm formation in static and dynamic biofilm models. qRT-PCR and protease activity assays demonstrated that under standard growth conditions, sepA is repressed by the global regulator SarA. Inactivation of sarA increased SepA production, and in turn augmented biofilm formation. Genetic and biochemical analyses demonstrated that SepA-related induction of biofilm accumulation resulted from enhanced Aap processing. Studies using recombinant proteins demonstrated that SepA is able to cleave the A domain of Aap at residue 335 and between the A and B domains at residue 601. This study identifies the mechanism behind Aap-mediated biofilm maturation, and also demonstrates a novel role for a secreted staphylococcal protease as a requirement for the development of a biofilm. This article is protected by copyright. All rights reserved.

U2 - 10.1111/mmi.13594

DO - 10.1111/mmi.13594

M3 - SCORING: Journal article

C2 - 27997732

VL - 103

SP - 860

EP - 874

JO - MOL MICROBIOL

JF - MOL MICROBIOL

SN - 0950-382X

IS - 5

ER -