scholarly journals Correspondence: Spontaneous secondary mutations confound analysis of the essential two-component system WalKR in Staphylococcus aureus

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Ian R. Monk ◽  
Benjamin P. Howden ◽  
Torsten Seemann ◽  
Timothy P. Stinear
Keyword(s):  
Staphylococcus Aureus ◽  
Two Component System ◽  
Component System ◽  
Two Component

scholarly journals The Staphylococcus aureus KdpDE Two-Component System Couples Extracellular K+Sensing and Agr Signaling to Infection Programming

2011 ◽  
Vol 79 (6) ◽  
pp. 2154-2167 ◽  
Author(s):  
Ting Xue ◽  
Yibo You ◽  
De Hong ◽  
Haipeng Sun ◽  
Baolin Sun
Keyword(s):  
Staphylococcus Aureus ◽  
Uptake System ◽  
Main Function ◽  
Two Component System ◽  
Component System ◽  
Content Type ◽  
Two Component ◽  
Virulence Regulator ◽  
External K

ABSTRACTThe Kdp system is widely distributed among bacteria. InEscherichia coli, the Kdp-ATPase is a high-affinity K+uptake system and its expression is activated by the KdpDE two-component system in response to K+limitation or salt stress. However, information about the role of this system in many bacteria still remains obscure. Here we demonstrate that KdpFABC inStaphylococcus aureusis not a major K+transporter and that the main function of KdpDE is not associated with K+transport but that instead it regulates transcription for a series of virulence factors through sensing external K+concentrations, indicating that this bacterium might modulate its infectious status through sensing specific external K+stimuli in different environments. Our results further reveal thatS. aureusKdpDE is upregulated by the Agr/RNAIII system, which suggests that KdpDE may be an important virulence regulator coordinating the external K+sensing and Agr signaling during pathogenesis in this bacterium.

scholarly journals Signaling mechanism by the Staphylococcus aureus two-component system LytSR: role of acetyl phosphate in bypassing the cell membrane electrical potential sensor LytS

F1000Research ◽  
2016 ◽  
Vol 4 ◽  
pp. 79 ◽  
Author(s):  
Kevin Patel ◽  
Dasantila Golemi-Kotra
Keyword(s):  
Staphylococcus Aureus ◽  
Membrane Potential ◽  
Cell Membrane ◽  
Electrical Potential ◽  
Cell Membrane Potential ◽  
Acetyl Phosphate ◽  
Two Component System ◽  
Component System ◽  
Two Component ◽  
Membrane Electrical Potential

The two-component system LytSR has been linked to the signal transduction of cell membrane electrical potential perturbation and is involved in the adaptation of Staphylococcus aureus to cationic antimicrobial peptides. It consists of a membrane-bound histidine kinase, LytS, which belongs to the family of multiple transmembrane-spanning domains receptors, and a response regulator, LytR, which belongs to the novel family of non-helix-turn-helix DNA-binding domain proteins. LytR regulates the expression of cidABC and lrgAB operons, the gene products of which are involved in programmed cell death and lysis. In vivo studies have demonstrated involvement of two overlapping regulatory networks in regulating the lrgAB operon, both depending on LytR. One regulatory network responds to glucose metabolism and the other responds to changes in the cell membrane potential. Herein, we show that LytS has autokinase activity and can catalyze a fast phosphotransfer reaction, with 50% of its phosphoryl group lost within 1 minute of incubation with LytR. LytS has also phosphatase activity. Notably, LytR undergoes phosphorylation by acetyl phosphate at a rate that is 2-fold faster than the phosphorylation by LytS. This observation is significant in lieu of the in vivo observations that regulation of the lrgAB operon is LytR-dependent in the presence of excess glucose in the medium. The latter condition does not lead to perturbation of the cell membrane potential but rather to the accumulation of acetate in the cell. Our study provides insights into the molecular basis for regulation of lrgAB in a LytR-dependent manner under conditions that do not involve sensing by LytS.

scholarly journals Disruption of Glycolysis by Nutritional Immunity Activates a Two-Component System That Coordinates a Metabolic and Antihost Response by Staphylococcus aureus

mBio ◽  
2019 ◽  
Vol 10 (4) ◽  
Author(s):  
Paola K. Párraga Solórzano ◽  
Jiangwei Yao ◽  
Charles O. Rock ◽  
Thomas E. Kehl-Fie
Keyword(s):  
Staphylococcus Aureus ◽  
Metabolic Flux ◽  
Bacterial Species ◽  
Critical Role ◽  
Dependent Manner ◽  
Two Component System ◽  
Component System ◽  
Content Type ◽  
Nutritional Immunity ◽  
Two Component

ABSTRACT During infection, bacteria use two-component signal transduction systems to sense and adapt to the dynamic host environment. Despite critically contributing to infection, the activating signals of most of these regulators remain unknown. This also applies to the Staphylococcus aureus ArlRS two-component system, which contributes to virulence by coordinating the production of toxins, adhesins, and a metabolic response that enables the bacterium to overcome host-imposed manganese starvation. Restricting the availability of essential transition metals, a strategy known as nutritional immunity, constitutes a critical defense against infection. In this work, expression analysis revealed that manganese starvation imposed by the immune effector calprotectin or by the absence of glycolytic substrates activates ArlRS. Manganese starvation imposed by calprotectin also activated the ArlRS system even when glycolytic substrates were present. A combination of metabolomics, mutational analysis, and metabolic feeding experiments revealed that ArlRS is activated by alterations in metabolic flux occurring in the latter half of the glycolytic pathway. Moreover, calprotectin was found to induce expression of staphylococcal leukocidins in an ArlRS-dependent manner. These studies indicated that ArlRS is a metabolic sensor that allows S. aureus to integrate multiple environmental stresses that alter glycolytic flux to coordinate an antihost response and to adapt to manganese starvation. They also established that the latter half of glycolysis represents a checkpoint to monitor metabolic state in S. aureus. Altogether, these findings contribute to understanding how invading pathogens, such as S. aureus, adapt to the host during infection and suggest the existence of similar mechanisms in other bacterial species. IMPORTANCE Two-component regulatory systems enable bacteria to adapt to changes in their environment during infection by altering gene expression and coordinating antihost responses. Despite the critical role of two-component systems in bacterial survival and pathogenesis, the activating signals for most of these regulators remain unidentified. This is exemplified by ArlRS, a Staphylococcus aureus global regulator that contributes to virulence and to resisting host-mediated restriction of essential nutrients, such as manganese. In this report, we demonstrate that manganese starvation and the absence of glycolytic substrates activate ArlRS. Further investigations revealed that ArlRS is activated when the latter half of glycolysis is disrupted, suggesting that S. aureus monitors flux through the second half of this pathway. Host-imposed manganese starvation also induced the expression of pore-forming toxins in an ArlRS-dependent manner. Cumulatively, this work reveals that ArlRS acts as a sensor that links nutritional status, cellular metabolism, and virulence regulation.

scholarly journals The Staphylococcus aureus ArlRS two‐component system regulates virulence factor expression through MgrA

2019 ◽  
Vol 113 (1) ◽  
pp. 103-122 ◽  
Author(s):  
Heidi A. Crosby ◽  
Nitija Tiwari ◽  
Jakub M. Kwiecinski ◽  
Zhen Xu ◽  
Allison Dykstra ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Virulence Factor ◽  
Two Component System ◽  
Component System ◽  
Two Component ◽  
Factor Expression

scholarly journals In the Staphylococcus aureus Two-Component System sae, the Response Regulator SaeR Binds to a Direct Repeat Sequence and DNA Binding Requires Phosphorylation by the Sensor Kinase SaeS

2010 ◽  
Vol 192 (8) ◽  
pp. 2111-2127 ◽  
Author(s):  
Fei Sun ◽  
Chunling Li ◽  
Dowon Jeong ◽  
Changmo Sohn ◽  
Chuan He ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Dna Binding ◽  
Response Regulator ◽  
Direct Repeat ◽  
Repeat Sequence ◽  
Sensor Kinase ◽  
Two Component System ◽  
Component System ◽  
Direct Repeat Sequence ◽  
Two Component

ABSTRACT Staphylococcus aureus uses the SaeRS two-component system to control the expression of many virulence factors such as alpha-hemolysin and coagulase; however, the molecular mechanism of this signaling has not yet been elucidated. Here, using the P1 promoter of the sae operon as a model target DNA, we demonstrated that the unphosphorylated response regulator SaeR does not bind to the P1 promoter DNA, while its C-terminal DNA binding domain alone does. The DNA binding activity of full-length SaeR could be restored by sensor kinase SaeS-induced phosphorylation. Phosphorylated SaeR is more resistant to digestion by trypsin, suggesting conformational changes. DNase I footprinting assays revealed that the SaeR protection region in the P1 promoter contains a direct repeat sequence (GTTAAN6GTTAA [where N is any nucleotide]). This sequence is critical to the binding of phosphorylated SaeR. Mutational changes in the repeat sequence greatly reduced both the in vitro binding of SaeR and the in vivo function of the P1 promoter. From these results, we concluded that SaeR recognizes the direct repeat sequence as a binding site and that binding requires phosphorylation by SaeS.

scholarly journals VfrB Is a Key Activator of the Staphylococcus aureus SaeRS Two-Component System

2016 ◽  
Vol 199 (5) ◽  
Author(s):  
Christina N. Krute ◽  
Kelly C. Rice ◽  
Jeffrey L. Bose
Keyword(s):  
Staphylococcus Aureus ◽  
Fatty Acid ◽  
Virulence Factors ◽  
Virulence Factor ◽  
Class I ◽  
Exponential Growth Phase ◽  
Two Component System ◽  
Component System ◽  
Content Type ◽  
Two Component

ABSTRACT In previous studies, we identified the fatty acid kinase virulence factor regulator B (VfrB) as a potent regulator of α-hemolysin and other virulence factors in Staphylococcus aureus. In this study, we demonstrated that VfrB is a positive activator of the SaeRS two-component regulatory system. Analysis of vfrB, saeR, and saeS mutant strains revealed that VfrB functions in the same pathway as SaeRS. At the transcriptional level, the promoter activities of SaeRS class I (coa) and class II (hla) target genes were downregulated during the exponential growth phase in the vfrB mutant, compared to the wild-type strain. In addition, saePQRS expression was decreased in the vfrB mutant strain, demonstrating a need for this protein in the autoregulation of SaeRS. The requirement for VfrB-mediated activation was circumvented when SaeS was constitutively active due to an SaeS (L18P) substitution. Furthermore, activation of SaeS via human neutrophil peptide 1 (HNP-1) overcame the dependence on VfrB for transcription from class I Sae promoters. Consistent with the role of VfrB in fatty acid metabolism, hla expression was decreased in the vfrB mutant with the addition of exogenous myristic acid. Lastly, we determined that aspartic acid residues D38 and D40, which are predicted to be key to VfrB enzymatic activity, were required for VfrB-mediated α-hemolysin production. Collectively, this study implicates VfrB as a novel accessory protein needed for the activation of SaeRS in S. aureus. IMPORTANCE The SaeRS two-component system is a key regulator of virulence determinant production in Staphylococcus aureus. Although the regulon of this two-component system is well characterized, the activation mechanisms, including the specific signaling molecules, remain elusive. Elucidating the complex regulatory circuit of SaeRS regulation is important for understanding how the system contributes to disease causation by this pathogen. To this end, we have identified the fatty acid kinase VfrB as a positive regulatory modulator of SaeRS-mediated transcription of virulence factors in S. aureus. In addition to describing a new regulatory aspect of SaeRS, this study establishes a link between fatty acid kinase activity and virulence factor regulation.

scholarly journals Two-component system VraSR positively modulates the regulation of cell-wall biosynthesis pathway in Staphylococcus aureus

2004 ◽  
Vol 49 (3) ◽  
pp. 807-821 ◽  
Author(s):  
Makoto Kuroda ◽  
Hiroko Kuroda ◽  
Taku Oshima ◽  
Fumihiko Takeuchi ◽  
Hirotada Mori ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Cell Wall Biosynthesis ◽  
Biosynthesis Pathway ◽  
Two Component System ◽  
Component System ◽  
Two Component
Sign in / Sign up

Export Citation Format

Share Document