sarA negatively regulates Staphylococcus epidermidis biofilm formation by modulating expression of 1 MDa extracellular matrix binding protein and autolysis-dependent release of eDNA.
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sarA negatively regulates Staphylococcus epidermidis biofilm formation by modulating expression of 1 MDa extracellular matrix binding protein and autolysis-dependent release of eDNA. / Christner, Martin; Heinze, Constanze; Busch, Michael; Franke, Gefion; Hentschke, Moritz; Sara, Bayard Dühring; Büttner, Henning; Kotasinska, Marta; Wischnewski, Victoria; Kroll, Gesche; Buck, Friedrich; Molin, Soeren; Otto, Michael; Rohde, Holger.
In: MOL MICROBIOL, Vol. 86, No. 2, 2, 2012, p. 394-410.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - sarA negatively regulates Staphylococcus epidermidis biofilm formation by modulating expression of 1 MDa extracellular matrix binding protein and autolysis-dependent release of eDNA.
AU - Christner, Martin
AU - Heinze, Constanze
AU - Busch, Michael
AU - Franke, Gefion
AU - Hentschke, Moritz
AU - Sara, Bayard Dühring
AU - Büttner, Henning
AU - Kotasinska, Marta
AU - Wischnewski, Victoria
AU - Kroll, Gesche
AU - Buck, Friedrich
AU - Molin, Soeren
AU - Otto, Michael
AU - Rohde, Holger
PY - 2012
Y1 - 2012
N2 - Biofilm formation is essential for Staphylococcus epidermidis pathogenicity in implant-associated infections. Nonetheless, large proportions of invasive Staphylococcus epidermidis isolates fail to form a biofilm in vitro. We here tested the hypothesis that this apparent paradox is related to the existence of superimposed regulatory systems suppressing a multicellular biofilm life style in vitro. Transposon mutagenesis of clinical significant but biofilm-negative S.?epidermidis 1585 was used to isolate a biofilm positive mutant carrying a Tn917 insertion in sarA, chief regulator of staphylococcal virulence. Genetic analysis revealed that inactivation of sarA induced biofilm formation via overexpression of the giant 1?MDa extracellular matrix binding protein (Embp), serving as an intercellular adhesin. In addition to Embp, increased extracellular DNA (eDNA) release significantly contributed to biofilm formation in mutant 1585?sarA. Increased eDNA amounts indirectly resulted from upregulation of metalloprotease SepA, leading to boosted processing of autolysin AtlE, in turn inducing augmented autolysis and release of eDNA. Hence, this study identifies sarA as a negative regulator of Embp- and eDNA-dependent biofilm formation. Given the importance of SarA as a positive regulator of polysaccharide mediated cell aggregation, the regulator enables S.?epidermidis to switch between mechanisms of biofilm formation, ensuring S.?epidermidis adaptation to hostile environments.
AB - Biofilm formation is essential for Staphylococcus epidermidis pathogenicity in implant-associated infections. Nonetheless, large proportions of invasive Staphylococcus epidermidis isolates fail to form a biofilm in vitro. We here tested the hypothesis that this apparent paradox is related to the existence of superimposed regulatory systems suppressing a multicellular biofilm life style in vitro. Transposon mutagenesis of clinical significant but biofilm-negative S.?epidermidis 1585 was used to isolate a biofilm positive mutant carrying a Tn917 insertion in sarA, chief regulator of staphylococcal virulence. Genetic analysis revealed that inactivation of sarA induced biofilm formation via overexpression of the giant 1?MDa extracellular matrix binding protein (Embp), serving as an intercellular adhesin. In addition to Embp, increased extracellular DNA (eDNA) release significantly contributed to biofilm formation in mutant 1585?sarA. Increased eDNA amounts indirectly resulted from upregulation of metalloprotease SepA, leading to boosted processing of autolysin AtlE, in turn inducing augmented autolysis and release of eDNA. Hence, this study identifies sarA as a negative regulator of Embp- and eDNA-dependent biofilm formation. Given the importance of SarA as a positive regulator of polysaccharide mediated cell aggregation, the regulator enables S.?epidermidis to switch between mechanisms of biofilm formation, ensuring S.?epidermidis adaptation to hostile environments.
KW - Humans
KW - Bacterial Proteins/genetics/metabolism
KW - Gene Expression Regulation, Bacterial
KW - Down-Regulation
KW - Adhesins, Bacterial/genetics/metabolism
KW - Bacteriolysis
KW - Biofilms
KW - DNA, Bacterial/genetics/metabolism
KW - Staphylococcus epidermidis/genetics/physiology
KW - Trans-Activators/genetics/metabolism
KW - Humans
KW - Bacterial Proteins/genetics/metabolism
KW - Gene Expression Regulation, Bacterial
KW - Down-Regulation
KW - Adhesins, Bacterial/genetics/metabolism
KW - Bacteriolysis
KW - Biofilms
KW - DNA, Bacterial/genetics/metabolism
KW - Staphylococcus epidermidis/genetics/physiology
KW - Trans-Activators/genetics/metabolism
M3 - SCORING: Journal article
VL - 86
SP - 394
EP - 410
JO - MOL MICROBIOL
JF - MOL MICROBIOL
SN - 0950-382X
IS - 2
M1 - 2
ER -
