Dysregulation of transition metal ion homeostasis is the molecular basis for cadmium toxicity in Streptococcus pneumoniae 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
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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 investigated how cadmium (Cd²⁺) affects the homeostasis of transition metal ions in Streptococcus pneumoniae. It focused on how Cd²⁺ competes with manganese (Mn²⁺) and zinc (Zn²⁺) for uptake and accumulation in the bacterium, leading to a disturbance in its metal ion balance and an increase in oxidative stress. Using a combination of assays, structural analyses, and growth experiments, the study revealed the mechanisms by which Cd²⁺ disrupts the bacterial metal uptake and efflux systems, particularly targeting the Psa permease responsible for manganese acquisition.
Who was studied?
The study focused on Streptococcus pneumoniae (S. pneumoniae), a Gram-positive bacterium. This organism was selected due to its reliance on a single manganese-specific uptake system, the PsaBCA permease. Researchers explored how the exposure to cadmium, a non-physiological metal ion, interferes with the bacterium’s homeostasis of essential metals like manganese and zinc. The study involved various mutant strains of S. pneumoniae to examine how different metal ion transporters and homeostatic systems contribute to the bacterium’s response to cadmium exposure.
Most important findings
The study uncovered how cadmium disrupts manganese and zinc homeostasis in Streptococcus pneumoniae. Cadmium competes with manganese for the Psa permease, significantly reducing manganese accumulation and enhancing the upregulation of the manganese efflux pathway (MntE). This disruption causes oxidative stress due to decreased manganese availability for the enzyme superoxide dismutase (SodA). Additionally, cadmium affects zinc homeostasis by triggering the upregulation of the zinc-efflux transporter CzcD, leading to a depletion of intracellular zinc. This dysregulation of both manganese and zinc disrupts the function of zinc-responsive transcriptional regulators such as AdcR and SczA, ultimately impairing the bacterium’s ability to manage oxidative stress.
Key implications
This study highlights the complex mechanisms by which cadmium disrupts metal ion homeostasis in bacteria. The findings provide insight into how environmental pollutants like cadmium can impair bacterial function by disturbing essential processes like metal ion uptake and oxidative stress management. These insights are crucial for developing new therapeutic strategies to mitigate the harmful effects of cadmium exposure, particularly in microorganisms.