Bacterial hyperpolarization modulated by polyoxometalates for solutions of antibiotic resistance

Developing strategies against the antibiotic resistance is a major global challenge for public health. Here, we report the synergy of the combination of Preyssler-type polyoxometalates (POMs) ([NaP₅W₃₀O₁₁₀]^14- or [AgP₅W₃₀O₁₁₀]^14-) and ribosome-targeting antibiotics for high antibacterial efficiency with low risk of antibiotic resistance. Due to their ultra-small sizes and active surface ligands, POM anions show strong affinity to bacterial cell membrane and impose hyperpolarization of the bacterial cells as well as the decrease of Mg²⁺ influx by blocking Mg²⁺ transporters, which finally lead to the structural perturbations of ribosomes and instability of bacterial structures. The bacterial growth can, therefore, be regulated by the presence of POMs: a fraction of Bacillus subtilis shifted to a 'dormant', slow-growing cellular state (an extended lag phase) upon the application of subinhibitory concentration of POMs. An approach to combat antibiotic resistant bacteria by applying POMs at their early growth phase followed by antibiotic exposure is validated, and its high efficiency for bacterial control is confirmed.