CadC, the transcriptional regulatory protein of the cadmium resistance system of Staphylococcus aureus plasmid pI258 Original paper
Researched by:
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Divine Aleru
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Divine Aleru
Read MoreI am a biochemist with a deep curiosity for the human microbiome and how it shapes human health, and I enjoy making microbiome science more accessible through research and writing. With 2 years experience in microbiome research, I have curated microbiome studies, analyzed microbial signatures, and now focus on interventions as a Microbiome Signatures and Interventions Research Coordinator.
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Metals
Metals
OverviewHeavy metals play a significant and multifaceted role in the pathogenicity of microbial species. Their involvement can be viewed from two primary perspectives: the toxicity of heavy metals to microbes and the exploitation of heavy metals by microbial pathogens to establish infections and evade the host immune response. Understanding these aspects is critical for both […]
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Microbes
Microbes
Microbes, short for microorganisms, are tiny living organisms that are ubiquitous in the environment, including on and inside the human body. They play a crucial role in human health and disease, functioning within complex ecosystems in various parts of the body, such as the skin, mouth, gut, and respiratory tract. The human microbiome, which is […]
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Divine Aleru
Read More
Researched by:
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Divine Aleru
ID
Divine Aleru
Read More
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Divine Aleru
What was studied?
This study examined the cadmium (Cd) resistance system in Staphylococcus aureus plasmid pI258, specifically focusing on the role of the CadC protein as a transcriptional regulator of the cadA gene. The cadA gene encodes a P-type ATPase responsible for the energy-dependent efflux of cadmium ions. The study aimed to characterize the function of CadC, the protein involved in regulating the cadmium resistance operon, and how it controls the expression of the cadA gene, particularly in response to cadmium exposure. The research further explored how CadC interacts with the cadA operator/promoter region and the effect of cadmium and other metal ions on this regulatory mechanism.
Who was studied?
The study involved Staphylococcus aureus strain pI258, which contains the cadA cadmium resistance operon. The CadC protein was studied by overexpressing it in Escherichia coli cells for subsequent purification. The research utilized various in vitro techniques, including gel retardation assays and DNase I footprinting assays, to analyze the interaction between CadC and the cadA operator/promoter DNA. The study also compared the cadmium resistance regulation in S. aureus with other resistance mechanisms, such as those found in the arsenic resistance system.
Most important findings
The study found that the CadC protein from S. aureus pI258 is a key transcriptional regulator of the cadA operon. In gel retardation assays, CadC bound specifically to the cadA operator/promoter region, resulting in a shift in DNA mobility, indicating a direct interaction between CadC and the DNA. This interaction was shown to be metal-dependent, with cadmium (Cd²⁺), bismuth (Bi³⁺), and lead (Pb²⁺) causing the release of CadC from the DNA in a concentration-dependent manner. DNase I footprinting assays revealed that CadC protected specific regions of the DNA from degradation, particularly between nucleotide positions 27 and 114 relative to the transcription start point. The study also showed that CadC represses transcription of the cadA gene, with this repression relieved in the presence of Cd²⁺, suggesting that CadC functions as a repressor that is regulated by cadmium ions.
Key implications
The study reveals that CadC is a crucial regulatory protein that controls cadmium resistance in S. aureus by binding to the cadA promoter and inhibiting its transcription. The metal-dependent regulation of CadC provides important insights into how bacteria manage toxic metal exposure. Understanding how CadC operates and interacts with other metal ions may aid in the development of therapeutic strategies to counteract cadmium toxicity or exploit similar mechanisms for environmental or industrial applications. The study also underscores the complexity of heavy metal resistance systems in bacteria and the role of metal-responsive regulatory proteins in maintaining bacterial survival in toxic environments.
Cadmiun (Cd)
Cadmium (Cd) is a highly toxic heavy metal commonly found in industrial, agricultural, and environmental settings. Exposure to cadmium can occur through contaminated water, food, soil, and air, and it has been linked to a variety of health issues, including kidney damage, osteoporosis, and cancer. In agriculture, cadmium is often present in phosphate fertilizers and can accumulate in plants, entering the food chain. Its toxicity to living organisms makes cadmium a subject of regulatory concern worldwide, particularly in industrial waste disposal and environmental monitoring.
Staphylococcus aureus (S. Aureus)
Staphylococcus aureus is a versatile skin and mucosal commensal that can transition into a highly virulent pathobiont. Known for its immune-evasive strategies, toxin production, and antibiotic resistance, it plays a significant role in chronic infections and microbiome imbalance.