Analysis of Staphylococcus aureus persister cells and their roles in infection

• Applicant: Professor Dr. Friedrich Götz, since 1/2014
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2008 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 72005236

Staphylococcus aureus is capable of forming biofilms, which probably constitute reservoirs for so called persister cells. These represent a subpopulation of a bacterial culture, are metabolically rather inactive, non dividing and display enhanced antibiotic tolerance. It can be assumed that bacteria in the viable but non-culturable (VBNC) state exhibit a related pattern of dormancy. We aim to reveal possible roles of VBNC/persister cells in chronic infections and address this issue by exploiting self-established S. aureus model systems. Cells selected for antibiotic tolerance or starved for mevalonate (both resembling a VBCN/persister-state) will be subjected to transcriptome, intracellular metabolome and host-cell interaction analyses. In order to identify factors associated with the persister-state, forward- and reverse genetics approaches will be taken. Naïve S. aureus persisters might be selected using dim GFP fluorescence and FACS and genes differently expressed in normal vs. persister cells will be targeted. Furthermore, an S. aureus genomic library will be screened and genes, the putative homologs of which have been described as “persister genes” in other bacteria will be analyzed. Revealing factors associated with VBNC/persister states in S. aureus and establishing respective stable or inducible S. aureus models will allow delineating correlations to the small colony variant phenotype and shedding light on the physiology and the interaction of dormant S. aureus bacteria with host cells.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1316: Host-adapted Metabolism of Bacterial Pathogens
• Ehemaliger Antragsteller: Privatdozent Dr. Ralph Alexander Bertram, until 1/2014