title: Phenotypic heterogeneity and temporal expression of the capsular polysaccharide in Staphylococcus aureus.
abstract: Bacteria respond to ever-changing environments through several adaptive strategies. This includes mechanisms leading to a high degree of phenotypic variability within a genetically homogeneous population. In Staphylococcus aureus, the capsular polysaccharide (CP) protects against phagocytosis, but also impedes adherence to endothelial cells and/or matrix proteins. We analysed the regulation of core biosynthesis genes (capA-P) necessary for CP synthesis using single-cell assays (immunofluorescence and promoter-activity). In persistent human carriers, we found a distinct subpopulation of nasal S. aureus to be CP positive. In vitro, cap expression is also heterogeneous and strongly growth-phase dependent. We asked whether this peculiar expression pattern (earlyOff/lateHeterogen) is orchestrated by the quorum system Agr. We show that the Agr-driven effector molecule RNAIII promotes cap expression largely via inactivation of the repressor Rot. High NaCl, deletion of CodY or Sae also resulted in higher cap expression but did not change the earlyOFF/lateHeterogen expression pattern. Activity of the quorum system itself is largely homogenous and does not account for the observed heterogeneity of cap expression or the strictly growth phase dependent expression. Our findings are in contrast to the prevailing view that quorum sensing is the main driving force for virulence gene expression when bacterial cell densities increase.
authors: Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany.
authors: Shilpa E
authors: SE
authors: George
authors: Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany.|Centre for Infection Research (DZIF), Partner Site Tübingen, Tübingen, Germany.
authors: Tran
authors: T
authors: Nguyen
authors: Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany.
authors: Tobias
authors: T
authors: Geiger
authors: Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany.
authors: Christopher
authors: C
authors: Weidenmaier
authors: Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
authors: Jean C
authors: JC
authors: Lee
authors: Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany.
authors: Jan
authors: J
authors: Liese
authors: Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany.
authors: Christiane
authors: C
authors: Wolz
mesh_terms: D016667:Bacterial Capsules / Q000737:chemistry / Q000235:genetics*; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D009666:Nose / Q000382:microbiology; D010641:Phenotype; D011135:Polysaccharides, Bacterial / Q000096:biosynthesis / Q000235:genetics*; D011401:Promoter Regions, Genetic; D053038:Quorum Sensing; D012329:RNA, Bacterial / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism* / Q000472:pathogenicity; D014774:Virulence / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D011135:Polysaccharides, Bacterial; D012329:RNA, Bacterial; C096035:RNAIII, Staphylococcus aureus; D012097:Repressor Proteins