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Cell differentiation defines acute and chronic infection cell types in Staphylococcus aureus

Please always quote using this URN: urn:nbn:de:bvb:20-opus-170346
  • A central question to biology is how pathogenic bacteria initiate acute or chronic infections. Here we describe a genetic program for cell-fate decision in the opportunistic human pathogen Staphylococcus aureus, which generates the phenotypic bifurcation of the cells into two genetically identical but different cell types during the course of an infection. Whereas one cell type promotes the formation of biofilms that contribute to chronic infections, the second type is planktonic and produces the toxins that contribute to acute bacteremia. WeA central question to biology is how pathogenic bacteria initiate acute or chronic infections. Here we describe a genetic program for cell-fate decision in the opportunistic human pathogen Staphylococcus aureus, which generates the phenotypic bifurcation of the cells into two genetically identical but different cell types during the course of an infection. Whereas one cell type promotes the formation of biofilms that contribute to chronic infections, the second type is planktonic and produces the toxins that contribute to acute bacteremia. We identified a bimodal switch in the agr quorum sensing system that antagonistically regulates the differentiation of these two physiologically distinct cell types. We found that extracellular signals affect the behavior of the agr bimodal switch and modify the size of the specialized subpopulations in specific colonization niches. For instance, magnesium-enriched colonization niches causes magnesium binding to S. aureusteichoic acids and increases bacterial cell wall rigidity. This signal triggers a genetic program that ultimately downregulates the agr bimodal switch. Colonization niches with different magnesium concentrations influence the bimodal system activity, which defines a distinct ratio between these subpopulations; this in turn leads to distinct infection outcomes in vitro and in an in vivo murine infection model. Cell differentiation generates physiological heterogeneity in clonal bacterial infections and helps to determine the distinct infection types.show moreshow less

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Metadaten
Author: Juan-Carlos García-BetancurORCiD, Angel Goñi-Moreno, Thomas Horger, Melanie Schott, Malvika Sharan, Julian EikmeierORCiD, Barbara Wohlmuth, Alma Zernecke, Knut Ohlsen, Christina Kuttler, Daniel LopezORCiD
URN:urn:nbn:de:bvb:20-opus-170346
Document Type:Journal article
Faculties:Medizinische Fakultät / Institut für Klinische Biochemie und Pathobiochemie
Medizinische Fakultät / Institut für Molekulare Infektionsbiologie
Language:English
Parent Title (English):eLife
Year of Completion:2017
Volume:6
Issue:e28023
Source:eLife 2017, 6:e28023. DOI: 10.7554/eLife.28023
DOI:https://doi.org/10.7554/eLife.28023
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:Staphylococcus aureus; cell differentiation; infection; pathogenic bacteria
Release Date:2019/09/23
EU-Project number / Contract (GA) number:335568
OpenAIRE:OpenAIRE
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International