Strategies to Block Bacterial Pathogenesis by Interference with Motility and Chemotaxis.

Abstract

Infections by motile, pathogenic bacteria, such as Campylobacter species, Clostridium species, Escherichia coli, Helicobacter pylori, Listeria monocytogenes, Neisseria gonorrhoeae, Pseudomonas aeruginosa, Salmonella species, Vibrio cholerae, and Yersinia species, represent a severe economic and health problem worldwide. Of special importance in this context is the increasing emergence and spread of multidrug-resistant bacteria. Due to the shortage of effective antibiotics for the treatment of infections caused by multidrug-resistant, pathogenic bacteria, the targeting of novel, virulence-relevant factors constitutes a promising, alternative approach. Bacteria have evolved distinct motility structures for movement across surfaces and in aqueous environments. In this review, I will focus on the bacterial flagellum, the associated chemosensory system, and the type-IV pilus as motility devices, which are crucial for bacterial pathogens to reach a preferred site of infection, facilitate biofilm formation, and adhere to surfaces or host cells. Thus, those nanomachines constitute potential targets for the development of novel anti-infectives that are urgently needed at a time of spreading antibiotic resistance. Both bacterial flagella and type-IV pili (T4P) are intricate macromolecular complexes made of dozens of different proteins and their motility function relies on the correct spatial and temporal assembly of various substructures. Specific type-III and type-IV secretion systems power the export of substrate proteins of the bacterial flagellum and type-IV pilus, respectively, and are homologous to virulence-associated type-III and type-II secretion systems. Accordingly, bacterial flagella and T4P represent attractive targets for novel antivirulence drugs interfering with synthesis, assembly, and function of these motility structures.