Stochastic Expression of Sae-Dependent Virulence Genes during Staphylococcus aureus Biofilm Development Is Dependent on SaeS

Authors

Elizabeth A. Delmain, University of Nebraska Medical CenterFollow
Derek E. Moormeier, University of Nebraska Medical Center
Jennifer L. Endres, University of Nebraska Medical CenterFollow
Rebecca E. Hodges, University of Nebraska Medical CenterFollow
Marat R. Sadykov, University of Nebraska Medical CenterFollow
Alexander R. Horswill, University of Colorado School of Medicine
Kenneth W. Bayles, University of Nebraska Medical CenterFollow

Document Type

Article

Journal Title

mBio

Publication Date

2020

Volume

11

Abstract

The intricate process of biofilm formation in the human pathogen Staphylococcus aureus involves distinct stages during which a complex mixture of matrix molecules is produced and modified throughout the developmental cycle. Early in biofilm development, a subpopulation of cells detaches from its substrate in an event termed “exodus” that is mediated by SaePQRS-dependent stochastic expression of a secreted staphylococcal nuclease, which degrades extracellular DNA within the matrix, causing the release of cells and subsequently allowing for the formation of metabolically heterogenous microcolonies. Since the SaePQRS regulatory system is involved in the transcriptional control of multiple S. aureus virulence factors, the expression of several additional virulence genes was examined within a developing biofilm by introducing fluorescent gene reporter plasmids into wild-type S. aureus and isogenic regulatory mutants and growing these strains in a microfluidic system that supplies the bacteria with a constant flow of media while simultaneously imaging developing biofilms in 5-min intervals. This study demonstrated that multiple virulence genes, including nuc, were expressed stochastically within a specialized subpopulation of cells in nascent biofilms. We demonstrated that virulence genes regulated by SaePQRS were stochastically expressed in nearly all strains examined whereas Agr-regulated genes were expressed more homogenously within maturing microcolonies. The commonly used Newman strain contains a variant of SaeS (SaeS^P) that confers constitutive kinase activity to the protein and caused this strain to lack the stochastic expression pattern observed in other strain backgrounds. Importantly, repair of the SaeS^P allele resulting in reversion to the well-conserved SaeS^L allele found in other strains restored stochastic expression in this strain.

DOI Link

10.1128/mBio.03081-19

ISSN

2150-7511

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Delmain, Elizabeth A.; Moormeier, Derek E.; Endres, Jennifer L.; Hodges, Rebecca E.; Sadykov, Marat R.; Horswill, Alexander R.; and Bayles, Kenneth W., "Stochastic Expression of Sae-Dependent Virulence Genes during Staphylococcus aureus Biofilm Development Is Dependent on SaeS" (2020). Journal Articles: Pathology and Microbiology. 68.
https://digitalcommons.unmc.edu/com_pathmicro_articles/68