Targeting bacterial motility: Prospective therapeutic countermeasures

Microorganisms have developed several motility types regulated by environmental conditions in host colonization to support transmission and virulence. Targeting motility is a promising antivirulence strategy. Herein, the current and developing countermeasures targeting filament-based and gliding/sliding motility mechanisms, including assembly, structure, and secretion, are reviewed. Additionally, indirect strategies that influence motility, including targeting c-di-GMP signaling, quorum sensing, and the two-component system, are described. Biological interference with metabolites and bacteriophage, as well as the promising strategies are also addressed in the review. The limitation and challenges of antimotility interventions are critically analysed. Overall, targeting motility represents a novel antivirulence paradigm to disarm pathogens while minimizing selective pressure for resistance, pointing to a promising direction for future combination therapies.