Dictyostelium discoideum as a surrogate host–microbe model for antivirulence screening in Pseudomonas aeruginosa PAO1
Author
dc.contributor.author
Bravo Toncio, Catalina
Author
dc.contributor.author
Alvárez, Javiera A.
Author
dc.contributor.author
Campos, Francisca
Author
dc.contributor.author
Ortiz Severin, Javiera
Author
dc.contributor.author
Varas, Macarena
Author
dc.contributor.author
Cabrera Paucar, Ricardo
Author
dc.contributor.author
Lagos, Carlos F.
Author
dc.contributor.author
Chávez, Francisco P.
Admission date
dc.date.accessioned
2016-12-13T20:54:19Z
Available date
dc.date.available
2016-12-13T20:54:19Z
Publication date
dc.date.issued
2016
Cita de ítem
dc.identifier.citation
International Journal of Antimicrobial Agents 47 (2016) 403–409
es_ES
Identifier
dc.identifier.other
10.1016/j.ijantimicag.2016.02.005
Identifier
dc.identifier.uri
https://repositorio.uchile.cl/handle/2250/141862
Abstract
dc.description.abstract
The interest of the pharmaceutical industry in developing new antibiotics is decreasing, as established screening systems which identify compounds that kill or inhibit the growth of bacteria can no longer be used. Consequently, antimicrobial screening using classical minimum inhibitory concentration (MIC) measurements is becoming obsolete. The discovery of antimicrobial agents that specifically target a bacterial pathogen without affecting the host and its beneficial bacteria is a promising strategy. However, few host-microbe models are available for in vivo screening of novel antivirulence molecules. Here we designed high-throughput developmental assays in the social amoeba Dictyostelium discoideum to measure Pseudomonas aeruginosa virulence and to screen for novel antivirulence molecules without side effects to the host and its beneficial bacteria Kiebsiella aerogenes. Thirty compounds were evaluated that had been previously selected by virtual screening for inhibitors of P. aeruginosa PAO1 polyphosphate kinase 1 (PaPPK1) and diverse compounds with combined PPK1 inhibitory and antivirulence activities were identified. This approach demonstrates that D. discoideum is a suitable surrogate host for preliminary high-throughput screening of antivirulence agents and that PPK1 is a suitable target for developing novel antivirulence compounds that can be further validated in mammalian models. (C) 2016 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.