Pyridyl-Linked Hetero Hydrazones: Transmembrane H+/Cl- Symporters with Efficient Antibacterial Activity.

The development of potent antibacterial agents has become increasingly difficult as bacteria continue to evolve and develop resistance to antibiotics. It is therefore imperative to find effective antimicrobial agents that can address the evolving challenges posed by infectious diseases and antimicrobial resistance. Using artificial transmembrane ion transporters is an emerging and promising avenue to address this issue. We report pyridyl-linked hetero hydrazones as highly efficient transmembrane HCl symporters. These compounds offer an appropriate HCl binding site through cooperative protonation, followed by recognition of chloride ions. HCl transport by these compounds inhibits the growth of different Gram-negative bacterial strains with high efficacy by affecting the cell envelope homeostasis. This specific class of compounds holds substantial promise in the ongoing pursuit of developing highly efficient antibacterial agents.

An organelle-tethering mechanism couples flagellation to cell division in bacteria.

In some free-living and pathogenic bacteria, problems in the synthesis and assembly of early flagellar components can cause cell-division defects. However, the mechanism that couples cell division with the flagellar biogenesis has remained elusive. Herein, we discover the regulator MadA that controls transcription of flagellar and cell-division genes in Caulobacter crescentus. We demonstrate that MadA, a small soluble protein, binds the type III export component FlhA to promote activation of FliX, which in turn is required to license the conserved σ54-dependent transcriptional activator FlbD. While in the absence of MadA, FliX and FlbD activation is crippled, bypass mutations in FlhA restore flagellar biogenesis and cell division. Furthermore, we demonstrate that MadA safeguards the divisome stoichiometry to license cell division. We propose that MadA has a sentinel-type function that senses an early flagellar biogenesis event and, through cell-division control, ensures that a flagellated offspring emerges.