Activation of the alternative sigma factor SigB of Staphylococcus aureus following internalization by epithelial cells – An in vivo proteomics perspective

Pförtner, Henrike; Burian, Marc; Michalik, Stephan; Depke, Maren; Hildebrandt, Petra; Dhople, Vishnu M.; Pané‐Farré, Jan; Hecker, Michael; Schmidt, Frank; Völker, Uwe

doi:10.1016/j.ijmm.2013.11.014

Cited by 27 publications

(28 citation statements)

References 47 publications

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“…The roles of SarA in these in vivo studies cannot be compared because only Horsburgh et al (142) specifically investigated sarA expression levels. It is conceivable that B acts as a modulator of virulence in S. aureus, a conclusion that has been put forward by several authors (54,146,147) and is supported by a recent study that evaluated the role of B during intracellular growth of S. aureus in a host cell line (148). This study showed B -dependent changes in the expression of several genes at the mRNA and protein levels.…”

Section: B In Pathogenesissupporting

confidence: 52%

Resilience in the Face of Uncertainty: Sigma Factor B Fine-Tunes Gene Expression To Support Homeostasis in Gram-Positive Bacteria

Guldimann

Boor

Wiedmann

et al. 2016

Appl Environ Microbiol

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Gram-positive bacteria are ubiquitous and diverse microorganisms that can survive and sometimes even thrive in continuously changing environments. The key to such resilience is the ability of members of a population to respond and adjust to dynamic conditions in the environment. In bacteria, such responses and adjustments are mediated, at least in part, through appropriate changes in the bacterial transcriptome in response to the conditions encountered. Resilience is important for bacterial survival in diverse, complex, and rapidly changing environments and requires coordinated networks that integrate individual, mechanistic responses to environmental cues to enable overall metabolic homeostasis. In many Gram-positive bacteria, a key transcriptional regulator of the response to changing environmental conditions is the alternative sigma factor B . B has been characterized in a subset of Gram-positive bacteria, including the genera Bacillus, Listeria, and Staphylococcus. Recent insight from nextgeneration-sequencing results indicates that B -dependent regulation of gene expression contributes to resilience, i.e., the coordination of complex networks responsive to environmental changes. This review explores contributions of B to resilience in Bacillus, Listeria, and Staphylococcus and illustrates recently described regulatory functions of B .

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Section: B In Pathogenesissupporting

confidence: 52%

Resilience in the Face of Uncertainty: Sigma Factor B Fine-Tunes Gene Expression To Support Homeostasis in Gram-Positive Bacteria

Guldimann

Boor

Wiedmann

et al. 2016

Appl Environ Microbiol

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“…However, our finding that repression of the rbs operon by RbsR, but not activation of capsule, is controlled by ribose suggests that ribose is not likely an effector linking the two cellular processes. On the other hand, because RbsR is highly regulated by SigB, whose activity is affected by certain in vitro and in vivo stress conditions (53)(54)(55), stress signals that modulate SigB activity are likely to be important effectors for controlling the quantity of RbsR, thereby affecting ribose uptake and capsule production. However, determining which signals are involved and how transduction of these signals through SigB affects the expression of RbsR requires further indepth studies.…”

Section: Discussionmentioning

confidence: 99%

RbsR Activates Capsule but Represses the rbsUDK Operon in Staphylococcus aureus

Lei

Lee

2015

J Bacteriol

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Staphylococcus aureus capsule is an important virulence factor that is regulated by a large number of regulators. Capsule genes are expressed from a major promoter upstream of the cap operon. A 10-bp inverted repeat (IR) located 13 bp upstream of the ؊35 region of the promoter was previously shown to affect capsule gene transcription. However, little is known about transcriptional activation of the cap promoter. To search for potential proteins which directly interact with the cap promoter region (Pcap), we directly analyzed the proteins interacting with the Pcap DNA fragment from shifted gel bands identified by electrophoretic mobility shift assay. One of these regulators, RbsR, was further characterized and found to positively regulate cap gene expression by specifically binding to the cap promoter region. Footprinting analyses showed that RbsR protected a DNA region encompassing the 10-bp IR. Our results further showed that rbsR was directly controlled by SigB and that RbsR was a repressor of the rbsUDK operon, involved in ribose uptake and phosphorylation. The repression of rbsUDK by RbsR could be derepressed by D-ribose. However, D-ribose did not affect RbsR activation of capsule. IMPORTANCEStaphylococcus aureus is an important human pathogen which produces a large number of virulence factors. We have been using capsule as a model virulence factor to study virulence regulation. Although many capsule regulators have been identified, the mechanism of regulation of most of these regulators is unknown. We show here that RbsR activates capsule by direct promoter binding and that SigB is required for the expression of rbsR. These results define a new pathway wherein SigB activates capsule through RbsR. Our results further demonstrate that RbsR inhibits the rbs operon involved in ribose utilization, thereby providing an example of coregulation of metabolism and virulence in S. aureus. Thus, this study further advances our understanding of staphylococcal virulence regulation. Staphylococcus aureus produces a large number of virulence factors that endow the organism with the ability to cause a wide range of diseases in humans and animals. The expression of virulence genes is controlled by an equally impressive number of regulators forming a complex regulatory network (1-3). Although the regulation of virulence genes has been the subject of extensive studies recently, our knowledge of the virulence regulatory network in S. aureus is still fragmented. To further understand virulence regulation, we have been studying the S. aureus virulence regulatory network by employing capsule as a model virulence factor (4-7). Capsule is an antiphagocytic virulence factor, and the majority of S. aureus strains produce either type 5 or type 8 capsule (8, 9). Sixteen cap genes, which are organized as a long operon, are required for the biosynthesis of either type of capsule (10). The genetic loci for the type 5 and type 8 capsules (cap5 and cap8) are allelic, with the four genes in the middle of the operon being type specific...

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“…We carried out the experiments using the techniques described by Pfortner et al with some modifications (29). Bacterial internalizations were performed as described above.…”

Section: Methodsmentioning

confidence: 99%

Role of the Tet38 Efflux Pump in Staphylococcus aureus Internalization and Survival in Epithelial Cells

et al. 2015

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bWe previously identified the protein Tet38 as a chromosomally encoded efflux pump of Staphylococcus aureus that confers resistance to tetracycline and certain unsaturated fatty acids. Tet38 also contributes to mouse skin colonization. In this study, we discovered a novel regulator of tet38, named tetracycline regulator 21 (TetR21), that bound specifically to the tet38 promoter and repressed pump expression. A ⌬tetR21 mutant showed a 5-fold increase in tet38 transcripts and an 8-fold increase in resistance to tetracycline and fatty acids. The global regulator MgrA bound to the tetR21 promoter and indirectly repressed the expression of tet38. To further assess the full role of Tet38 in S. aureus adaptability, we tested its effect on host cell invasion using A549 (lung) and HMEC-1 (heart) cell lines. We used S. aureus RN6390, its ⌬tet38, ⌬tetR21, and ⌬mgrA mutants, and a ⌬tet38 ⌬tetR21 double mutant. After 2 h of contact, the ⌬tet38 mutant was internalized in 6-fold-lower numbers than RN6390 in A549 and HMEC-1 cells, and the ⌬tetR21 mutant was internalized in 2-fold-higher numbers than RN6390. A slight increase of 1.5-fold in internalization was found for the ⌬mgrA mutant. The growth patterns of RN6390 and the ⌬mgrA and ⌬tetR21 mutants within A549 cells were similar, while no growth was observed for the ⌬tet38 mutant. These data indicate that the Tet38 efflux pump is regulated by TetR21 and contributes to the ability of S. aureus to internalize and replicate within epithelial cells.

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Activation of the alternative sigma factor SigB of Staphylococcus aureus following internalization by epithelial cells – An in vivo proteomics perspective

Cited by 27 publications

References 47 publications

Resilience in the Face of Uncertainty: Sigma Factor B Fine-Tunes Gene Expression To Support Homeostasis in Gram-Positive Bacteria

Resilience in the Face of Uncertainty: Sigma Factor B Fine-Tunes Gene Expression To Support Homeostasis in Gram-Positive Bacteria

RbsR Activates Capsule but Represses the rbsUDK Operon in Staphylococcus aureus

Role of the Tet38 Efflux Pump in Staphylococcus aureus Internalization and Survival in Epithelial Cells

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