title: 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.
authors.affiliation: Helmholtz Centre for Infection Research, Inhoffenstr. 7, 38124, Braunschweig, Germany. marc.erhardt@helmholtz-hzi.de.
authors.forename: Marc
authors.initials: M
authors.lastname: Erhardt
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000166:cytology / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity*; D001424:Bacterial Infections / Q000382:microbiology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects*; D006801:Humans; D014774:Virulence / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins