Resistance to antibiotics — caused by overuse in humans and excessive addition to animal feed — is a growing problem. Pathogenic strains of Escherichia coli are particularly difficult to control, having an exceptional ability to undergo rapid adaptive mutations that render antibiotics ineffective. E. coli is also an example of what is known as a ‘Gram-negative’ bacteria, with an additional outer membrane that protects the bacteria against certain antibiotics.

Fig. 1: Schematic representation showing the antibacterial action of the light-activated electrostatic complex.

Now, Shu Wang from the Beijing Chinese Academy of Sciences1 and collaborators have developed an alternative approach to address E. coli drug-resistance. They designed a new light-responsive complex that efficiently generates singlet oxygen — a form of oxygen that reacts rapidly with biomolecules to ultimately kill E. coli cells (Fig. 1).

The team created the complex by synthesizing a positively charged porphyrin (TPPN) and combining it with a negatively charged polythiophene (PTP) through electrostatic interactions. TPPN is a large, planar compound that readily sensitizes molecular oxygen through energy transfer to produce singlet oxygen when exposed to light, and PTP is an organic polymer that captures and transfers light energy. The combined PTP–TPPN complex thus generates singlet oxygen efficiently when exposed to light.

“Anionic polythiophene can form a complex with cationic porphyrin without requiring covalent linkage, which reduces complicated synthetic procedures,” says Wang. “The electrostatic interactions keep them in close proximity to meet the requirement for energy transfer and singlet oxygen generation.”

At least three times as much PTP as TPPN was required to optimize singlet oxygen production, demonstrating the importance of PTP in maximizing energy transfer within the light-activated complex. Under these conditions, the resulting complex was positively charged and could bind to the negatively charged outer bacterial membrane of E. coli. The PTP–TPPN complex killed 70% of the bacteria within 5 min upon exposure to white light.

“The positive charge of the PTP–TPPN complex promotes its adsorption to the negatively charged membrane of bacteria through electrostatic interactions,” says Wang.

Futhermore, by showing that the PTP–TPPN complex achieved near-quantitative inactivation of Bacillus subtilis (a Gram-positive bacterium), the researchers also established that their approach could be used to destroy other types of bacteria. They are currently investigating how to adapt this technique to anticancer therapy.