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

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-form...

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Bibliographic Details
Published in:Biomolecules (Basel, Switzerland) Switzerland), 2021-01, Vol.11 (1), p.55
Main Authors: Sundin, Charlotta, Saleeb, Michael, Spjut, Sara, Qin, Liena, Elofsson, Mikael
Format: Article
Language:English
Subjects:
Antibiotics
Antimicrobial agents
Biofilms
biologi
biology
Cell membranes
Cystic fibrosis
Cytoplasm
Cytotoxins
Drug resistance
Enzymes
Immune system
infection
Infections
Laboratories
Macrophages
Mortality
Mutation
NMR
Nuclear magnetic resonance
Opportunist infection
Organic Chemistry
organisk kemi
Pathogens
PcrV
Polyamines
Pore-forming proteins
Proteins
Pseudomonas aeruginosa
screening
small molecules
Surface plasmon resonance
type III secretion
type III secretion system
Virulence
virulence inhibitors
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Summary: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 cell-based infection assay. Treatment of 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 .
ISSN:2218-273X
2218-273X
DOI:10.3390/biom11010055