Targets for bacterial resistance: recent advances in small-molecule FtsZ inhibitors

ESKAPE pathogens (including <i>Staphylococcus aureus</i>, <i>Enterococcus faecalis</i>, <i>Klebsiella pneumoniae</i>, <i>Acinetobacter baumannii</i>, <i>Pseudomonas aeruginosa</i>, and <i>Enterobacteriaceae</i>) represent a core challenge in the global antimicrobial resistance (AMR) crisis. Their multidrug resistance and high transmissibility pose severe clinical threats. However, the pharmaceutical industry's current motivation for developing new drugs targeting these resistant bacteria remains insufficient. Consequently, creating antibiotics with novel mechanisms of action has become a strategic imperative for safeguarding global public health security. Therefore, targeting the bacterial cell division core protein filamentous heat-sensitive Z (FtsZ) has emerged as a key strategy to address the AMR crisis. FtsZ exhibits high conservation and prokaryotic specificity, making it an ideal target for developing novel antimicrobial agents. This paper systematically reviews the structural and functional mechanisms of FtsZ and summarizes research progress on inhibitors targeting its GTPase activity or assembly process - including natural products, synthetic small molecules, peptides, and nanomaterials - based on their sources and structural types. Consequently, drug development targeting FtsZ holds promise as a breakthrough solution for treating infections caused by drug-resistant bacteria such as ESKAPE pathogens.