Identification of Small Molecules Blocking the Pseudomonas aeruginosa Type III Secretion System Protein PcrV

Sundin, Charlotta; Saleeb, Michael; Spjut, Sara; Qin, Liena; Elofsson, Mikael

doi:10.3390/biom11010055

Open AccessArticle

Identification of Small Molecules Blocking the Pseudomonas aeruginosa Type III Secretion System Protein PcrV

by

Charlotta Sundin

^*,

Michael Saleeb

,

Sara Spjut

,

Liena Qin

and

Mikael Elofsson

Department of Chemistry, Umeå University, SE-901 87 Umeå, Sweden

^*

Author to whom correspondence should be addressed.

Biomolecules 2021, 11(1), 55; https://doi.org/10.3390/biom11010055

Submission received: 26 November 2020 / Revised: 21 December 2020 / Accepted: 29 December 2020 / Published: 4 January 2021

(This article belongs to the Special Issue Virulence Systems of Human Pathogens as Targets for Novel Therapeutics and Prophylactics)

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Abstract

Pseudomonas aeruginosa is an opportunistic bacterial pathogen that employs its type III secretion system (T3SS) during the acute phase of infection to translocate cytotoxins into the host cell cytoplasm to evade the immune system. The PcrV protein is located at the tip of the T3SS, facilitates the integration of pore-forming proteins into the eukaryotic cell membrane, and is required for translocation of cytotoxins into the host cell. In this study, we used surface plasmon resonance screening to identify small molecule binders of PcrV. A follow-up structure-activity relationship analysis resulted in PcrV binders that protect macrophages in a P. aeruginosa cell-based infection assay. Treatment of P. aeruginosa infections is challenging due to acquired, intrinsic, and adaptive resistance in addition to a broad arsenal of virulence systems such as the T3SS. Virulence blocking molecules targeting PcrV constitute valuable starting points for development of next generation antibacterials to treat infections caused by P. aeruginosa.

Keywords: Pseudomonas aeruginosa; type III secretion system; PcrV; virulence inhibitors; screening; surface plasmon resonance; infection

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MDPI and ACS Style

Sundin, C.; Saleeb, M.; Spjut, S.; Qin, L.; Elofsson, M. Identification of Small Molecules Blocking the Pseudomonas aeruginosa Type III Secretion System Protein PcrV. Biomolecules 2021, 11, 55. https://doi.org/10.3390/biom11010055

AMA Style

Sundin C, Saleeb M, Spjut S, Qin L, Elofsson M. Identification of Small Molecules Blocking the Pseudomonas aeruginosa Type III Secretion System Protein PcrV. Biomolecules. 2021; 11(1):55. https://doi.org/10.3390/biom11010055

Chicago/Turabian Style

Sundin, Charlotta, Michael Saleeb, Sara Spjut, Liena Qin, and Mikael Elofsson. 2021. "Identification of Small Molecules Blocking the Pseudomonas aeruginosa Type III Secretion System Protein PcrV" Biomolecules 11, no. 1: 55. https://doi.org/10.3390/biom11010055

APA Style

Sundin, C., Saleeb, M., Spjut, S., Qin, L., & Elofsson, M. (2021). Identification of Small Molecules Blocking the Pseudomonas aeruginosa Type III Secretion System Protein PcrV. Biomolecules, 11(1), 55. https://doi.org/10.3390/biom11010055

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Identification of Small Molecules Blocking the Pseudomonas aeruginosa Type III Secretion System Protein PcrV

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