Copper economy helps fungi and bacteria form stronger biofilms

Copper economy helps fungi and bacteria form stronger biofilms

Researchers have identified a biological mechanism they call a copper economy that allows two common human pathogens to cooperate and build more resilient biofilms. The discovery suggests that the management of this specific micronutrient is what enables a fungus and a bacterium to work together, potentially offering new strategies to dismantle stubborn mixed infections.

The study focused on the fungus Candida albicans and the bacterium Staphylococcus aureus. Both are major causes of human infection and are frequently found together in bloodstream infections, wounds, and infections associated with medical devices. When these microbes form biofilms—structured communities attached to surfaces and embedded in a self-produced matrix—they become significantly harder to treat than single-species infections.

Led by Dr Seána Duggan from the University of Exeter's MRC Centre for Medical Mycology, the team grew the two species together in laboratory conditions designed to mimic the human body. Using biofilms formed on plastic, the researchers found that the dual-species communities were consistently larger and more active than biofilms formed by either microbe alone.

The cooperation is driven by non-reciprocal copper handling. Proteomic analysis revealed that C. Albicans increased its copper uptake via the transporter Ctr1. Simultaneously, S. Aureus increased proteins linked to copper stress protection and copper export, specifically via the regulator CsoR and export chaperone CopZ.

"We usually think about copper as something that can kill microbes, because high levels are toxic. Our study reveals something more nuanced. In these mixed biofilms, copper appears to act almost like a shared currency that helps two very different pathogens cooperate,"

Dr Seána Duggan, University of Exeter, via miragenews.com

This balance is fragile. The researchers discovered that the mixed biofilm was much more sensitive to copper disruption than either organism was individually. Both the limitation of copper and an excess of copper weakened the community and reduced its biomass. Specifically, copper-replete conditions compromised the role of fungal hyphae, which serve as a critical scaffold for the physical architecture of the biofilm.

While the primary focus was on S. Aureus, the study extended these findings to show that the copper import mechanisms of C. Albicans also facilitate mutualistic interactions with other bacterial species.

The implications extend beyond clinical settings. Fungal biofilms are also prevalent in aquatic environments, ranging from fresh and marine waters to domestic and healthcare water supplies. In these niches, fungi interact with bacteria, protozoa, and algae to break down organic matter and cycle nutrients. In some cases, species such as Aspergillus establish biofilms on pipe surfaces, which provides resistance to standard disinfection and creates risks for immunocompromised people. Research into these aquatic communities has linked shifts in species diversity and antifungal resistance to physicochemical parameters, including heavy metal concentrations.

For medical applications, the discovery of the copper economy provides a potential therapeutic target. Early tests suggest that copper-based approaches, including the use of copper nanoparticles, can disrupt these dual-species biofilms.

"If we can identify the conditions that make these microbial partnerships fail, we may be able to design better ways to break them apart,"

Dr Seána Duggan, University of Exeter, via miragenews.com

The research was supported by the NIHR Exeter Biomedical Research Centre and published in Microbiology under the title Copper Driven Mutualism of Candida albicans and Staphylococcus aureus Interkingdom Biofilms.