A revolutionary advancement in microbial engineering has emerged from the laboratories of Politecnico di Milano, where researchers have devised an innovative method to control bacterial behavior through light, without resorting to genetic modification. This pioneering approach, known as the Engineering Of bacteria to See light (EOS) project, exploits the power of photo-sensitive molecules to manipulate bacterial electrical activity, representing a significant leap forward in the fight against antibiotic resistance—a global health crisis of mounting concern. By harnessing light to influence bacterial membrane potentials, scientists can now remotely regulate functions such as motility, biofilm development, and antibiotic sensitivity, opening up new frontiers in microbial therapeutics and biotechnology.
Traditional strategies to combat antibiotic resistance have often relied on developing new drugs or genetically modifying pathogens, both fraught with considerable challenges. The EOS project circumvents these hurdles by employing photo-transducing molecules that bind irreversibly to bacterial surfaces. These molecules act as transducers, converting external light stimuli into electrical signals that traverse the bacterial membrane. This optoelectronic manipulation alters the membrane potential — the voltage difference across the bacterial membrane — a fundamental bioelectrical parameter pivotal in many cellular processes. This light-responsive control “dial” offers unprecedented precision in modulating bacterial physiology, achievable simply by adjusting light exposure parameters without altering the bacteria’s genetic code.
At the molecular level, the EOS team has incorporated a photosensitive molecule known as Ziapin2 onto the membranes of Bacillus subtilis, a model Gram-positive bacterium. Ziapin2 responds to blue light illumination at 470 nanometers by inducing changes in the membrane’s electrical potential, effectively “hijacking” bacterial signaling pathways. This process, termed optomodulation, can finely tune the bacteria’s uptake mechanisms and bioelectrical states related to antibiotic resistance. The team demonstrated that this photomodulation could diminish the efficacy of certain antibiotics such as Kanamycin by reducing their cellular uptake. Conversely, antibiotics like Ampicillin, whose target resides in the bacterial cell wall rather than the cytoplasm, maintained their potency under photoactivation conditions, highlighting the nuanced relationship between membrane potential and antimicrobial action.
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By leveraging these insights, the EOS project heralds a new paradigm in antimicrobial therapy. Light-activated molecules can be used to create next-generation antimicrobial platforms, where precise spatiotemporal control of bacterial susceptibility to antibiotics becomes a reality. Beyond mere antibiotic enhancement, this technology promises the creation of biocompatible, light-guided “bacterial robots.” These engineered bacteria could be programmed to transport and release pharmaceutical compounds selectively to sites within the human body that are otherwise challenging to treat, such as the complex environment of the gastrointestinal tract. Such specificity would revolutionize targeted drug delivery while minimizing systemic side effects.
The implications of this research extend beyond therapeutic applications into fundamental microbial physiology and biophysics. The ability to non-invasively modulate bacterial membrane potential through light expands our toolkit for dissecting bacterial electrical signaling and its influence on cellular decision-making processes, including biofilm formation—a major cause of chronic infections and antibiotic resistance. By fine-tuning electrical gradients, researchers can now investigate bacterial communication and survival strategies with unparalleled precision, potentially revealing novel antimicrobial targets.
What distinguishes this technology from previous approaches is its non-reliance on genetic modification, broadening its applicability across diverse bacterial species and strains. Genetic engineering, while powerful, carries regulatory and ethical considerations, especially when dealing with pathogenic microorganisms. The EOS methodology sidesteps these concerns by exploiting a chemical-physical interface between the bacterial membrane and photoresponsive molecules, enabling reversible and externally controllable modulation of bacterial function without altering the organism’s DNA.
Furthermore, the interdisciplinary nature of the EOS project fuels its rapid advancement. It draws on expertise from physics, chemistry, materials science, and microbiology, merging photochemistry and electrochemistry principles with cutting-edge microbial research. This convergence enables the design of exquisitely tuned molecules like Ziapin2, optimized for stability, membrane integration, and efficient photoresponse, as well as sophisticated experimental setups to quantify membrane potential shifts and antibiotic uptake under various illumination regimes.
Funding from the European Research Council, through a highly competitive ERC Starting Grant totaling €1.5 million under the Horizon Europe program, has provided vital resources for this cutting-edge initiative launched in 2023. The recognition of Dr. Giuseppe Maria Paternò, EOS project’s scientific coordinator, as an “Ambassador for the ERC Network” underscores the societal and scientific importance of such innovative research. This acknowledgment also positions the project as a beacon advocating for the indispensable role of curiosity-driven research and technology development in addressing pressing global challenges such as antimicrobial resistance.
The experimental evidence published in The European Physical Journal Plus furnishes compelling data that light-controlled modulation of membrane potential directly impacts antibiotic persistence in Bacillus subtilis. The intricate experiments detail how blue light exposure dynamically alters bacterial electrical properties, modulating the intracellular concentration and effectiveness of antimicrobial agents. Such tunable control over bacterial physiology via optical means is a groundbreaking addition to microbial pharmacology, offering researchers novel strategies to resensitize resistant strains.
Moreover, this light-mediated approach aligns seamlessly with rapidly burgeoning fields such as synthetic biology and bioelectronics. The ability to “wire” bacteria with photo-transducing molecules bridges biological systems and electronic interfaces, opening possibilities for programmable microbial systems that respond to external stimuli with engineered precision. The EOS project therefore not only addresses antibiotic resistance but also contributes foundational knowledge valuable for the development of biohybrid devices and living sensors.
In conclusion, the EOS project’s innovative exploitation of light-sensitive chemical agents affixed to bacteria heralds a transformative era in microbiology and antimicrobial therapeutics. By controlling bacterial membrane potential through optomodulation, researchers have revealed a novel axis for influencing antibiotic uptake and resistance, achieved without genetic interference. This elegant intervention, enabled by fundamental interdisciplinary research, foretells a future where bacteria can be remotely controlled to combat infections, deliver drugs, and serve as components of advanced biomedical devices. As antibiotic resistance continues to threaten global health, such groundbreaking technologies offer hope for sustainable, precise, and responsive strategies to restore and enhance antibiotic efficacy, ultimately saving lives and preserving the utility of vital antimicrobial drugs.
Subject of Research: Not applicable
Article Title: Photocontrol of bacterial membrane potential regulates antibiotic persistence in B. subtilis
News Publication Date: 24-Apr-2025
Web References: http://dx.doi.org/10.1140/epjp/s13360-025-06263-7
References: The European Physical Journal Plus (Springer Nature), DOI: 10.1140/epjp/s13360-025-06263-7
Image Credits: Politecnico di Milano – Department of Physics
Keywords: Antibiotic resistance, Bacterial defenses, Bacterial physiology, Bacterial growth, Bacteriology, Research methods, Microbiology, Cell biology, Biophysics, Molecular biology, Molecular physiology, Membrane biophysics, Chemical biology, Biochemistry, Photoelectrochemistry, Electrochemistry, Photochemistry, Chemical processes, Chemical engineering
Tags: advanced microbial therapeuticsantibiotic resistance solutionsbacterial behavior controlbacterial membrane potential manipulationbiofilm development and controlEngineering Of bacteria to See light projectinnovative methods in synthetic biologylight-based microbial engineeringoptoelectronic strategies in biotechnologyovercoming antibiotic resistance challengesphoto-sensitive molecules in microbiologyremote regulation of bacterial functions
