FTS Inhibitors

Fts (Filamentous temperature-sensitive) proteins play a fundamental role in bacterial cell division, serving as key components of the division machinery. Consequently, inhibiting these proteins has garnered significant attention as a strategy for combating bacterial infections. Chemical compounds known as Fts inhibitors have emerged as a class of molecules designed to disrupt or interfere with the essential functions of Fts proteins, thereby impeding the bacterial cell division process. These inhibitors target various components of the cell division machinery, with a primary focus on FtsZ, an essential and highly conserved protein in bacterial cell division.

FtsZ inhibitors are characterized by their ability to interfere with FtsZ polymerization, a crucial step in the formation of the Z-ring, a dynamic structure that pinches the bacterial cell membrane during division. One class of FtsZ inhibitors includes compounds that bind to the GTP-binding site of FtsZ, thereby disrupting the hydrolysis of GTP and disrupting the assembly of FtsZ into protofilaments, which are essential for Z-ring formation. These inhibitors can be small molecules or natural products and typically feature structural elements that mimic GTP, allowing them to compete with GTP for binding to FtsZ. Another class of Fts inhibitors includes compounds that target the FtsZ polymerization interface, obstructing the lateral interactions between FtsZ protofilaments and disrupting the proper bundling of these structures. The result is a destabilized Z-ring or the formation of non-functional FtsZ aggregates, ultimately impairing bacterial cell division. Additionally, some Fts inhibitors work by binding to other Fts proteins, such as FtsA or ZipA, which are crucial for anchoring FtsZ to the cell membrane and stabilizing the Z-ring. By interfering with these interactions, Fts inhibitors disrupt the coordinated assembly of the cell division machinery, leading to division defects and bactericidal effects.