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Identification of a Potent Inhibitor of Type II Secretion System From Pseudomonas Aeruginosa

Identification of a Potent Inhibitor of Type II Secretion System From Pseudomonas Aeruginosa

Wieslaw Swietnicki, Anna Czarny, Lukasz Antkowiak, Ewa Zaczynska, Monika Kolodziejczak, Jordan Sycz, Lukasz Stachowicz, Michalina Alicka, Krzysztof Marycz

Biochem Biophys Res Commun. 2019 Jun 4;513(3):688-693.

PMID: 30987825

Abstract:

Pseudomonas aeruginosa is an opportunistic pathogen infecting human population. The pathogen is becoming a serious health problem due to its ability to evade normal immune response of the host and multiple drug resistance to many antibiotics. The pathogen has 2 major virulence systems of which the type III secretion system (T3SS) is of major concern to humans. A third system, type 2 secretion system (T2SS), is common to bacteria and used to secrete exotoxin A (ExoA) responsible for human cell destruction. To help bypass the drug resistance, a strategy to block the T2SS based on a low similarity between human ATPases and the essential ATPases of the T3SS and T2SS of P. aeruginosa, was used. An in silico-optimized inhibitor of T3SS, made directly from the computer-optimized of previously published compounds and their combinatorial libraries, showed IC50 = 1.3 ± 0.2 μM in the T2SS ExoA secretion blocking test. The compound was non-toxic to human lung epithelial cell line A549 and could block cellular destruction of those cells in a cell infection model at 200 μM for at least 24 h. The compound could be a lead candidate for the development of T2SS virulence blockers of Pseudomonas aeruginosa.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP91262952	Pseudomonas exotoxin A from Pseudomonas aeruginosa		91262-95-2	Price

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