Role of Copper Efflux in Pneumococcal Pathogenesis and Resistance to Macrophage-Mediated Immune Clearance Original paper

Researched by:

  • Divine Aleru ID
    Divine Aleru

    User avatarI 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.

    Read More

September 5, 2025

  • 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 […]

  • 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 […]

Researched by:

  • Divine Aleru ID
    Divine Aleru

    User avatarI 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.

    Read More

Last Updated: 2025-09-05

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

I 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.

What was studied?

This study explores the role of copper efflux systems, particularly the copA gene, in the pathogenesis of Streptococcus pneumoniae and its ability to resist copper toxicity during infection. The copA gene encodes a copper efflux pump that is crucial for bacterial survival under conditions of excess copper. The research investigates how S. pneumoniae uses copper efflux to avoid macrophage-mediated killing, a key host immune defense. By studying the mutant strains of S. pneumoniae that lack the copA gene, the researchers assess the bacterium’s ability to survive copper-induced stress and its overall virulence in different infection models.

Who was studied?

The study focused on Streptococcus pneumoniae, a bacterium responsible for diseases like pneumonia, meningitis, and otitis media. The researchers used the S. pneumoniae strain TIGR4 for their experiments and created mutant strains lacking the copA, cupA, and copY genes. They also assessed macrophage-mediated killing of these strains in vitro to determine the role of copper efflux in bacterial survival under immune attack. The experiments included both wild-type and mutant strains of S. pneumoniae to compare their ability to withstand copper toxicity in host tissues.

Most important findings

The study found that the copper efflux system, specifically the copA gene, plays a critical role in the virulence of S. pneumoniae. The copA mutant exhibited a significantly reduced ability to survive in animal models, with lower bacterial counts in the lungs and bloodstream compared to the wild-type strain. This suggests that copper efflux is essential for the bacterium’s ability to resist copper toxicity during infection. The study also showed that the copA mutant was more susceptible to macrophage-mediated killing, although the bacteria were still engulfed by macrophages at similar rates as the wild-type strain. This indicates that copper efflux is crucial for resisting the toxic effects of copper within macrophages, which is part of the host’s immune defense strategy.

When macrophages were depleted in the infected mice, the virulence defect of the copA mutant was partially rescued, further confirming the role of copper efflux in immune evasion. Interestingly, while the copA and cupA mutants both showed increased sensitivity to copper in vitro, only the copA mutant displayed significant attenuation of virulence in vivo. This highlights that the efflux of copper, rather than simply copper sensitivity, is essential for S. pneumoniae‘s ability to cause disease.

Key implications

The findings underscore the importance of copper homeostasis in bacterial pathogenesis, specifically how S. pneumoniae utilizes copper efflux to avoid the toxic effects of copper and survive within the host. The copA copper exporter plays a vital role in this process by preventing copper accumulation and enabling the bacteria to resist macrophage-mediated copper toxicity. These insights provide potential targets for new therapeutic strategies aimed at disrupting copper homeostasis in S. pneumoniae. Targeting the copper efflux systems could help weaken the pathogen’s ability to survive in the host and enhance the effectiveness of the immune response, particularly by preventing the bacterium from evading copper-induced toxicity.

Copper (Cu)

Copper serves as both a vital nutrient and a potential toxin, with its regulation having profound effects on microbial pathogenesis and immune responses. In the body, copper interacts with pathogens, either supporting essential enzyme functions or hindering microbial growth through its toxicity. The gastrointestinal tract, immune cells, and bloodstream are key sites where copper plays a crucial role in controlling infection and maintaining microbial balance. Understanding copper’s interactions with the microbiome and host defenses allows for targeted clinical strategies.

Join the Roundtable

Contribute to published consensus reports, connect with top clinicians and researchers, and receive exclusive invitations to roundtable conferences.