Recombinant Salmonella paratyphi A ATP-dependent Clp protease ATP-binding subunit ClpX (clpX)
Description
Introduction to Recombinant Salmonella paratyphi A ATP-dependent Clp Protease ATP-binding Subunit ClpX
The Recombinant Salmonella paratyphi A ATP-dependent Clp protease ATP-binding subunit ClpX, encoded by the clpX gene, is a crucial component of the ClpXP proteolytic complex. This complex plays a significant role in bacterial proteostasis, stress response, and virulence. ClpX acts as an ATPase that unfolds and translocates substrates to the ClpP protease for degradation, which is essential for maintaining protein homeostasis and regulating various cellular processes in bacteria.
Function and Mechanism of ClpX
ClpX is a hexameric ATPase that recognizes specific substrates, often tagged with degradation signals such as the SsrA tag, which is involved in the trans-translation process for ribosomal rescue . This recognition is critical for the degradation of aberrant or damaged proteins, ensuring cellular health and function. In pathogens like Salmonella, ClpX contributes to virulence by regulating stress responses and the turnover of proteins involved in pathogenicity .
Role in Salmonella Virulence
In Salmonella enterica serovar Typhimurium, ClpX is involved in the regulation of flagellar synthesis by degrading the FlhD master regulator, thus controlling flagellum production . Disruption of ClpX leads to a hyperflagellate phenotype, indicating its role in modulating motility, which is a key virulence factor . In Salmonella paratyphi A, mutations in clpX have been used to create attenuated strains for vaccine development, highlighting its importance in bacterial pathogenicity .
4.1. Vaccine Development
Mutations in the clpX gene have been utilized to develop attenuated vaccine strains of Salmonella paratyphi A. For example, the CVD 1902 strain, which lacks clpX and guaBA, has shown promise as a live attenuated vaccine, eliciting immune responses without causing severe disease .
4.2. Molecular Mechanisms
Studies on ClpX have revealed its role in recognizing and degrading specific substrates. Mutations affecting this recognition can impact bacterial differentiation and development, as seen in Chlamydia . Similarly, in E. coli, mutations in ClpX can enhance motility by altering the degradation of regulatory proteins .
4.3. Implications for Pathogenicity
The disruption of ClpX in Salmonella enterica serovar Typhimurium results in persistent infection rather than acute disease, indicating its role in systemic infection and survival within host cells . This persistence is influenced by host immune responses, particularly cytokines like IFN-γ and TNF-α .
Table 1: Functions and Implications of ClpX in Bacteria
| Function/Implication | Description | Organism |
|---|---|---|
| Virulence Regulation | Controls stress responses and protein turnover | Salmonella enterica serovar Typhimurium |
| Flagellar Synthesis | Regulates flagellum production by degrading FlhD | Salmonella enterica serovar Typhimurium |
| Vaccine Development | Used to create attenuated strains for vaccine development | Salmonella paratyphi A |
| Protein Degradation | Recognizes and degrades SsrA-tagged substrates | Chlamydia trachomatis |
| Motility Enhancement | Mutations can increase motility by altering regulatory protein degradation | Escherichia coli |
Table 2: Key Research Findings on ClpX
Product Specs
Target Background
ATP-dependent specificity component of the Clp protease; directs the protease to specific substrates. Exhibits chaperone functions independently of ClpP.
KEGG: spt:SPA2273
