The σ ^B -Dependent yabJ-spoVG Operon Is Involved in the Regulation of Extracellular Nuclease, Lipase, and Protease Expression in Staphylococcus aureus

Abstract

The alternative sigma factor B of Staphylococcus aureus is involved in the coordination of the general stress response, expression of virulence determinants, and modulation of antibiotic resistance levels. It controls a large regulon, either directly by recognizing conserved B promoter sequences or indirectly via B -dependent elements. The B -controlled yabJ-spoVG operon encodes two such putative downstream elements. We report here transcriptome analysis in S. aureus Newman, showing that inactivation of the yabJ-spoVG operon had primarily a repressing effect on a small subregulon encoding mainly virulence factors, including a nuclease (nuc), a protease (splE) and a lipase (lip). As a consequence, extracellular nuclease, protease, and lipase activities were reduced in a ⌬yabJ-spoVG mutant. trans-complementation by SpoVG was sufficient to restore their reduced phenotypic expression and lowered transcription due to the yabJ-spoVG deletion. It did not restore, however, the changes triggered by B inactivation, indicating that both regulons only partially overlap, despite the B dependency of the yabJ-spoVG expression. Thus, B is likely to control additional, SpoVGindependent factors affecting the expression of numerous hydrolytic enzymes. SpoVG, on the other hand, seems to fine-tune the B -dependent regulation of a subset of virulence factors by antagonizing the B effect.Staphylococcus aureus secretes a wide array of extracellular virulence factors that enable it to cause superficial skin infections or severe invasive infections, such as bacteremia, endocarditis, and osteomyelitis (4, 9, 18). The growth-and environmentdependent expression of virulence factors is a prerequisite for the survival of S. aureus in the host and the pathogenesis of staphylococcal infections. During initial colonization steps, the expression of cell surface adhesins promotes the binding to human extracellular matrix components (16). Extracellular enzymes, such as nucleases, lipases, and proteases, are, on the other hand, produced mainly in later infection stages. They destroy the local host tissue to access nutrients required for growth and spreading within the host (18) and facilitate immune evasion by interfering with the host's innate immune system (5, 41).The coordinated expression of virulence determinants in S. aureus is controlled by a complex network of regulatory elements, including two-component regulatory systems, DNAbinding proteins, and alternative sigma factors (8,13,32,53).B is the best characterized alternative sigma factor of S. aureus. It is involved in general stress responses (11,22,28,32,38) and part of the regulatory network controlling the expression of virulence determinants (25,28,31,54) and modulates antibiotic resistance levels (6,37,46,48,53).B activity is growth phase regulated, peaking toward early stationary phase (47), and controls a large regulon of genes involved in many different cellular processes by recognizing and binding to a conserved nucleotide consensus sequence (GTTTAA-12-15-G GGTAT) in the upstream ...

SigB Is a Dominant Regulator of Virulence in Staphylococcus aureus Small-Colony Variants

“…It was also reported that SigB prevents biofilm dispersion by repressing nuclease activity [40], which is a mechanism we also observed in the SCV CF07-S. Studying the molecular mechanisms controlling extracellular nuclease activity in SCVs should be of interest as SigB was also described to activate nuc1 expression through the SpoVG-dependent pathway [49]. Overall, SigB positively controls biofilm formation by at least two different mechanisms in the SCV CF07-S: it supports the expression of fnbA and represses nuclease activity.…”

Novel Pathways for Ameliorating the Fitness Cost of Gentamicin Resistant Small Colony Variants

“…The spoVG gene encodes for the downstream modulator SpoVG of the σ B general stress response (Schulthess et al, 2011), rsbU encodes for the RsbU activator of σ B (Hecker et al, 2007), while rpoF encodes for the alternative sigma factor SigB (σ B ) (Hecker et al, 2007). None of the seven sequenced lineages evolved with gentamicin had acquired mutations related to the σ B stress response.…”

SpoVG Regulates Cell Wall Metabolism and Oxacillin Resistance in Methicillin-Resistant Staphylococcus aureus Strain N315

“…In this study, we have also found that spoVG deletion can reduce oxacillin resistance in MRSA strain N315. SpoVG can directly regulate fmtB, which is one of the fem or aux genes (26,28). It has been reported that femA, also one of fem or aux genes, is involved in the synthesis of pentaglycin cross-links (5).…”

“…In nonsporulating bacteria, the B -controlled spoVG affects capsule synthesis, expression of virulence factors, and antibiotic resistance (25)(26)(27). SpoVG is considered a site-specific DNA-binding protein (28).…”