title: sarA negatively regulates Staphylococcus epidermidis biofilm formation by modulating expression of 1 MDa extracellular matrix binding protein and autolysis-dependent release of eDNA.
abstract: 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 1585ΔsarA. 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.
authors.affiliation: Institute for Medical Microbiology, Virology and Hygiene, University Medical Centre Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Christner
authors.forename: Constanze
authors.initials: C
authors.lastname: Heinze
authors.forename: Michael
authors.initials: M
authors.lastname: Busch
authors.forename: Gefion
authors.initials: G
authors.lastname: Franke
authors.forename: Moritz
authors.initials: M
authors.lastname: Hentschke
authors.forename: Sara
authors.initials: S
authors.lastname: Bayard Dühring
authors.forename: Henning
authors.initials: H
authors.lastname: Büttner
authors.forename: Marta
authors.initials: M
authors.lastname: Kotasinska
authors.forename: Victoria
authors.initials: V
authors.lastname: Wischnewski
authors.forename: Gesche
authors.initials: G
authors.lastname: Kroll
authors.forename: Friedrich
authors.initials: F
authors.lastname: Buck
authors.forename: Soeren
authors.initials: S
authors.lastname: Molin
authors.forename: Michael
authors.initials: M
authors.lastname: Otto
authors.forename: Holger
authors.initials: H
authors.lastname: Rohde
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics* / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001433:Bacteriolysis; D018441:Biofilms; D004269:DNA, Bacterial / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D013212:Staphylococcus epidermidis / Q000235:genetics / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
chemical_list: D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D004269:DNA, Bacterial; C088021:SarA protein, bacterial; D015534:Trans-Activators