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SPARKinfect: Cracking the Electrical Code of Staphylococcus aureus to Understand How Superbugs Survive in Different Environments

Project description

How Staphylococcus aureus electrical code affects bacterial persistence

Understanding the mechanisms enabling bacterial persistence during infection is crucial for addressing antimicrobial resistance, which is a major global challenge. The ERC-funded SPARKinfect project is establishing a new bioelectric framework to understand how membrane potential governs the physiology and survival of Staphylococcus aureus during intracellular infection. The project aims to show how electrical states change during infection. It also seeks to identify the mechanisms driving these adaptations and determine how they influence antibiotic susceptibility and persistence. By shedding light on membrane potential as a regulator of bacterial pathogenesis, SPARKinfect will lay the foundations for therapeutic strategies against antimicrobial-resistant infections.

Objective

The emergence of multidrug-resistant pathogens such as Staphylococcus aureus (MRSA) poses a global health threat. A central yet underexplored driver of bacterial survival is the membrane potential (Δψ), a fundamental electrical property that regulates energy transduction, cell division, and antibiotic susceptibility. Evidence indicates that Δψ is not a passive backdrop but an active regulator of physiology, enabling adaptation to stress. Yet no systematic framework quantifies or explains Δψ dynamics of S. aureus during infection.

SPARKinfect will focus on S. aureus bioelectric physiology during intracellular infection, where bacteria are shielded from antibiotics and immunity. Using Nernstian dyes and confocal–FLIM microscopy, I will build quantitative single-cell maps of Δψ in host cells with high temporal and spatial resolution. Comparative measurements in planktonic cultures and biofilms will serve as reference states to identify infection-specific electrical signatures. I will combine these data with host–pathogen co-culture, and antibiotic challenges to test how electrical states govern persistence and treatment outcomes.

The project will first establish how intracellular Δψ dynamics differ from those observed in extracellular lifestyles, then uncover the genetic determinants of electrophysiological adaptation using imaging of mutant libraries, and finally demonstrate how specific electrical states causally shape antibiotic uptake, activity, and survival outcomes. By linking single-cell physiology to infection and treatment, SPARKinfect will provide the first mechanistic framework to explain how Δψ underpins the persistence of S. aureus inside host cells.

The results will pioneer a bioelectric perspective on pathogenesis. Beyond basic science, SPARKinfect will yield insights into intracellular antibiotic tolerance, guide novel therapeutic strategies, and establish a versatile pipeline for microbial electrophysiology applicable to other priority pathogens.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

(opens in new window) HORIZON-WIDERA-2025-TALENTS-01

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Coordinator

UNIVERSIDADE NOVA DE LISBOA
Net EU contribution
€ 191 343,12
Address
CAMPUS DE CAMPOLIDE
1099-085 Lisboa
Portugal
Activity type
Higher or Secondary Education Establishments
Links
Total cost
No data