An Overview of Drugging the Bacterial Cytoskeleton, Rod, and Divisome Systems

Bacterial infections and antibiotic resistance remain significant threats to global health, with millions of related deaths recorded annually. Projections that antibacterial resistance-related deaths could reach alarming proportions in the coming years, along with the shortcomings of current interventions, highlight the need for new drug targets, novel antibiotics, and revised strategies and policy actions. The bacterial cytoskeleton, rod, and divisome systems (BCRDs) play vital cellular roles and serve as a reserve of numerous potential therapeutic targets. The components of the BCRDs play different functions but share some common proteins and interlinked roles, suggesting the possibility of exploiting synergistic, polytherapeutic, and polypharmacological effects with antibiotics to mitigate bacterial resistance. Unfortunately, few drug targets within the BCRDs have been validated, and bacterial resistance to the inhibitors and approved antibiotics poses a challenge to the health and pharmaceutical industries. This review provides a concise but comprehensive overview of drugging the BCRDs, emphasizing the functional relationships and druggable potentials, validated targets, inhibitors, challenges, interventions, prospects, perspectives, and future directions geared toward reinvigorating research and overcoming bottlenecks in the sector. Overall, the material presented and discussed could facilitate the identification and validation of new therapeutic targets, the discovery and development of novel clinical drugs, and the revision of strategies and policy interventions to augment the fight against antibiotic resistance.