Approaches targeting the type III secretion system to treat or prevent bacterial infections

Abstract

Introduction: The type III secretion system (T3SS) injectisome is an essential virulence mechanism used by many bacterial pathogens to inject host cells with effector proteins. Bacteria harboring T3SSs can cause significant disease in humans. As bacterial antibiotic resistance is a major concern, alternative prophylaxis and therapeutics are needed and T3SSs are a target for anti-virulence drugs.

Areas covered: In this article, the authors review whole-cell-based high-throughput screens (HTSs), which have been the main approach used to identify small molecules inhibiting T3SSs. The authors review this in the context of particular characteristics of T3SSs. Furthermore, they also describe the follow-up approaches used to study the inhibitors found. The authors also highlight target-based approaches to find inhibitors of specific T3SS components. Finally, the authors briefly review strategies used to find inhibitors of effectors or of effector-activated host cell pathways, and approaches based on T3SSs for active or passive immunization and rational vaccine design.

Expert opinion: Future efforts targeting T3SS to prevent or treat bacterial infections should focus on deciphering the mode of action of inhibitors and on target-based approaches. The aim should not only be to find anti-T3SS drugs but also to develop novel or improved vaccines. Continuous efforts to understand many remaining fundamental questions about the structure and function of T3SSs will also be needed.

Keywords:

• antibiotic resistance
• bacterial pathogenesis
• salicylidene acylhydrazides
• type III secretion systems
• virulence blockers

Declaration of interest

The authors are supported by the Fundação para a Ciência e a Tecnologia (FCT). N Charro is supported by a post-doctoral fellowship within FCT grant PTDC/BIA-MIC/116780/2010 , of which LJ Mota is the principal investigator. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Notes

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