Role of the alternative sigma factor SigB on antibiotic tolerance in Staphylococcus aureus

Staphylococcus aureus is a major human pathogen, responsible for numerous infections that, despite appropriate treatment, often become chronic or relapsing. The recurrence of infections is closely associated with the formation of bacterial persister cells. There, a subpopulation of bacteria becomes tolerant to the antibiotic treatment by entering a metabolic status of low activity (triggered persistence) or by heterogenous activation of different stress pathways (spontaneous persistence). Previous research suggested that S. aureus cells stochastically enter the stationary phase at any timepoint, which is accompanied by a drop of intracellular energy levels and results in persister formation. Bacteria expressing stationary phase markers such as activity of the capsular polysaccharide promotor (Pcap) are indicative for persisters (1). Recently, we could show that Pcap activity is mainly regulated by the alternative sigma factor B (SigB) (2). Thus, we hypothesized that SigB activity might be a trigger for persister formation in S. aureus. Pcap activity as well as the prototypic SigB target gene asp were shown to be heterogeneously expressed within a population, with maximum expression upon entering the stationary phase. We analysed S. aureus strain Newman and its sigB mutant for persister cell formation following treatment with various bactericidal antibiotics (vancomycin, gentamycin, daptomycin and ciprofloxacin). SigB had no impact on antibiotic resistance (MIC) or on persister cell formation in the exponential growth phase. However, the sigB mutant was less antibiotic tolerant when bacteria were grown to stationary phase. Repeated subculturing indicated that triggered persistence in S. aureus is SigB dependent while spontaneous persister formation seems to be independent of SigB. We aim to further elucidate the signals leading to SigB activation and thus persister formation on the single cell level.

(1) Conlon et al. (2016)

(2) Keinhörster et al. (2019)