1. Trends Pharmacol Sci. 2016 Sep;37(9):734-49. doi: 10.1016/j.tips.2016.05.011.
Epub 2016 Jun 22.

Targeting the Type Three Secretion System in Pseudomonas aeruginosa.

Anantharajah A(1), Mingeot-Leclercq MP(1), Van Bambeke F(2).

Author information: 
(1)Pharmacologie Cellulaire et Moléculaire, Louvain Drug Research Institute,
Université Catholique de Louvain, Brussels, Belgium. (2)Pharmacologie Cellulaire 
et Moléculaire, Louvain Drug Research Institute, Université Catholique de
Louvain, Brussels, Belgium. Electronic address:
francoise.vanbambeke@uclouvain.be.

The injectisome type three secretion system (T3SS) is a major virulence factor in
Pseudomonas aeruginosa. This bacterium is responsible for severe infections in
immunosuppressed or cystic fibrosis patients and has become resistant to many
antibiotics. Inhibitors of T3SS may therefore constitute an innovative
therapeutic target. After a brief description of the T3SS and its regulation,
this review presents strategies to inhibit T3SS-mediated toxicity and describes
the main families of existing inhibitors. Over the past few years, 12 classes of 
small-molecule inhibitors and two types of antibody have been discovered and
evaluated in vitro for their capacity to inhibit T3SS expression or function, and
to protect host cells from T3SS-mediated cytotoxicity. While only one small
molecule has been tested in vivo, a bifunctional antibody targeting both the
translocation apparatus of the T3SS and a surface polysaccharide is currently in 
Phase II clinical trials.

Copyright © 2016 Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.tips.2016.05.011 
PMID: 27344210  [PubMed - in process]