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Virulence blockers as alternatives to antibiotics: type III secretion inhibitors against Gram-negative bacteria
Umeå University, Faculty of Science and Technology, Chemistry. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
Umeå University, Faculty of Science and Technology, Molecular Biology (Faculty of Science and Technology). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
2008 (English)In: Journal of Internal Medicine, Vol. 264, no 1, 17-29 p.Article in journal (Refereed) Published
Abstract [en]

In recent years mounting problems related to antibiotic-resistant bacteria have resulted in the prediction that we are entering the preantibiotic era. A way of preventing such a development would be to introduce novel antibacterial medicines with modes of action distinct from conventional antibiotics. Recent studies of bacterial virulence factors and toxins have resulted in increased understanding of the way in which pathogenic bacteria manipulate host cellular processes. This knowledge may now be used to develop novel antibacterial medicines that disarm pathogenic bacteria. The type III secretion system (T3SS) is known to be a potent virulence mechanism shared by a broad spectrum of pathogenic Gram-negative bacteria that interact with human, animal and plant hosts by injecting effector proteins into the cytosol of host cells. Diseases, such as bubonic plague, shigellosis, salmonellosis, typhoid fever, pulmonary infections, sexually transmitted chlamydia and diarrhoea largely depend on the bacterial proteins injected by the T3SS machinery. Recently a number of T3SS inhibitors have been identified using screening-based approaches. One class of inhibitors, the salicylidene acylhydrazides, has been subjected to chemical optimization and evaluation in several in vitro and ex vivo assays in multiple bacterial species including Yersinia spp., Chlamydia spp., Salmonella spp. and Pseudotuberculosis aeruginosa. Reports published up to date indicate that T3SS inhibitors have the potential to be developed into novel antibacterial therapeutics.

Place, publisher, year, edition, pages
2008. Vol. 264, no 1, 17-29 p.
URN: urn:nbn:se:umu:diva-10085DOI: doi:10.1111/j.1365-2796.2008.01941.xOAI: diva2:149756
Available from: 2008-06-16 Created: 2008-06-16 Last updated: 2010-03-03Bibliographically approved

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Elofsson, MikaelWolf-Watz, Hans
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ChemistryUmeå Centre for Microbial Research (UCMR)Molecular Biology (Faculty of Science and Technology)Molecular Infection Medicine Sweden (MIMS)

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