The impact of serine/threonine phosphorylation in Staphylococcus aureus

Ohlsen, Knut; Donat, Stefanie

doi:10.1016/j.ijmm.2009.08.016

Cited by 77 publications

(90 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The presence of eukaryotic-like Ser/Thr kinase-phosphatase pairs in bacteria has fueled interests in elucidating their potential roles in bacterial signaling and regulation (53)(54)(55). The Stk1-Stp1 pair is conserved in Gram-positive bacteria and has been suggested to play global regulatory roles through Ser/Thr phosphorylation/dephosphorylation (6,9). We show here that this kinase/phosphatase pair can phosphorylate Cys residues in different proteins in Grampositive bacteria.…”

Section: Discussionmentioning

confidence: 69%

“…However, it wasn't until recently that eukaryotic-like Ser/Thr/Tyr phosphorylation in bacteria started to receive significant attention (6)(7)(8). Particularly, in pathogenic bacteria such as Mycobacterium tuberculosis and Staphylococcus aureus, eukaryotic-like Ser/Thr kinases (and associated phosphatases) have often been shown to participate in virulence functions (5,(9)(10)(11). The kinase/phosphatase pairs are known as Stks/Stps in bacteria; the kinase Stk1 has been called as PknB or Stk, and the phosphatase Stp1 as Stp (9).…”

mentioning

confidence: 99%

“…Particularly, in pathogenic bacteria such as Mycobacterium tuberculosis and Staphylococcus aureus, eukaryotic-like Ser/Thr kinases (and associated phosphatases) have often been shown to participate in virulence functions (5,(9)(10)(11). The kinase/phosphatase pairs are known as Stks/Stps in bacteria; the kinase Stk1 has been called as PknB or Stk, and the phosphatase Stp1 as Stp (9). Throughout this study, we will use Stk1 for the kinase and Stp1 for the phosphatase because these names are more common in the literature.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Protein cysteine phosphorylation of SarA/MgrA family transcriptional regulators mediates bacterial virulence and antibiotic resistance

Sun

Ding

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

158

170

View full text Add to dashboard Cite

Protein posttranslational modifications (PTMs), particularly phosphorylation, dramatically expand the complexity of cellular regulatory networks. Although cysteine (Cys) in various proteins can be subject to multiple PTMs, its phosphorylation was previously considered a rare PTM with almost no regulatory role assigned. We report here that phosphorylation occurs to a reactive cysteine residue conserved in the staphylococcal accessary regulator A (SarA)/MarR family global transcriptional regulator A (MgrA) family of proteins, and is mediated by the eukaryotic-like kinase-phosphatase pair Stk1-Stp1 in Staphylococcus aureus. Cys-phosphorylation is crucial in regulating virulence determinant production and bacterial resistance to vancomycin. Cell wall-targeting antibiotics, such as vancomycin and ceftriaxone, inhibit the kinase activity of Stk1 and lead to decreased Cys-phosphorylation of SarA and MgrA. An in vivo mouse model of infection established that the absence of stp1, which results in elevated protein Cys-phosphorylation, significantly reduces staphylococcal virulence. Our data indicate that Cys-phosphorylation is a unique PTM that can play crucial roles in bacterial signaling and regulation.

show abstract

Section: Discussionmentioning

confidence: 69%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Protein cysteine phosphorylation of SarA/MgrA family transcriptional regulators mediates bacterial virulence and antibiotic resistance

Sun

Ding

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

158

170

View full text Add to dashboard Cite

show abstract

“…Many of the stimuli encountered are transduced via sensor kinases in the membrane, allowing the pathogen to adapt for survival in hostile environments. In addition to the classical two-component systems, S. aureus contains one eukaryotic-like serine/threonine protein kinase (STPK), Stk1 (16,17). Recent studies provided the first insights into the regulatory function of Stk1 and the molecular mechanisms of the Ser/Thr phosphorylation system in S. aureus (17).…”

mentioning

confidence: 99%

“…In addition to the classical two-component systems, S. aureus contains one eukaryotic-like serine/threonine protein kinase (STPK), Stk1 (16,17). Recent studies provided the first insights into the regulatory function of Stk1 and the molecular mechanisms of the Ser/Thr phosphorylation system in S. aureus (17). Interestingly, the Ser/Thr kinase Stk1 was identified to influence central metabolic processes in S. aureus (18) and the activity of important regulatory factors such as SarA (19), MgrA (20), and LuxS (21).…”

mentioning

confidence: 99%

A Novel Mode of Regulation of the Staphylococcus aureus Catabolite Control Protein A (CcpA) Mediated by Stk1 Protein Phosphorylation

Leiba

Hartmann

Cluzel

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background:The catabolite control protein A (CcpA) plays an important role in Staphylococcus aureus virulence, biofilm formation, and central metabolism. Results: Phosphorylation of CcpA negatively affects its DNA binding activity and thus the expression of its target genes. Conclusion: CcpA activity is modulated by Stk1 phosphorylation. Significance: This study highlights that phosphorylation of CcpA represents a novel regulatory control mechanism for this major transcriptional factor.

show abstract

5,5′‐Methylenedisalicylic Acid (MDSA) Modulates SarA/MgrA Phosphorylation by Targeting Ser/Thr Phosphatase Stp1

et al. 2015

View full text Add to dashboard Cite

SarA (staphylococcal accessory protein A), MgrA (MarR family of global transcriptional regulator A), and SarZ (a paralogue of SarA) play critical roles in modulating the virulence, drug resistance and autolysis of Staphylococcus aureus. Recently, eukaryotic-like Ser/Thr kinase/phosphatases (Stk1/Stp1) were found to modulate phosphorylation of these transcriptional regulators as well as staphylococcal virulence. Importantly, an stp1-deficient strain showed significant virulence reduction in mice, indicative of Stp1 as a potential drug target. Here, we report that MDSA, an inhibitor of MgrA, enhances phosphorylation of SarA/MgrA by inhibiting Stp1 in S. aureus. MDSA is a more-potent inhibitor (IC50 =9.68 ± 0.52 μM) of Stp1 than commonly used phosphatase inhibitors. We anticipate that MDSA could be a lead compound to develop new approaches for reducing staph virulence by targeting Stp1.

show abstract

The impact of serine/threonine phosphorylation in Staphylococcus aureus

Cited by 77 publications

References 27 publications

Protein cysteine phosphorylation of SarA/MgrA family transcriptional regulators mediates bacterial virulence and antibiotic resistance

Protein cysteine phosphorylation of SarA/MgrA family transcriptional regulators mediates bacterial virulence and antibiotic resistance

A Novel Mode of Regulation of the Staphylococcus aureus Catabolite Control Protein A (CcpA) Mediated by Stk1 Protein Phosphorylation

5,5′‐Methylenedisalicylic Acid (MDSA) Modulates SarA/MgrA Phosphorylation by Targeting Ser/Thr Phosphatase Stp1

Contact Info

Product

Resources

About