Gabriele Sass1, Laura C Miller Conrad2, Terrence-Thang H Nguyen2, David A Stevens1,3. 1. California Institute for Medical Research, San Jose, CA 95128, USA. 2. Department of Chemistry, San Jose State University, San Jose, CA 95112, USA. 3. Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Abstract
BACKGROUND: Bacteria are sources of numerous molecules used in treatment of infectious diseases. We investigated effects of molecules produced by 26 Pseudomonas aeruginosa strains against infection of mammalian cell cultures with Trypanosoma cruzi, the aetiological agent of Chagas disease. METHODS: Vero cells were infected with T. cruzi in the presence of wild-type P. aeruginosa supernatants or supernatants of mutants with defects in the production of various virulence, quorum sensing and iron acquisition factors. Quantification of T. cruzi infection (percentage of infected cells) and multiplication (number of amastigotes per infected cell) was performed and cell viability was determined. RESULTS: Wild-type P. aeruginosa products negatively affected T. cruzi infection and multiplication in a dose-dependent manner, without evident toxicity for mammalian cells. PvdD/pchE mutation (loss of the P. aeruginosa siderophores pyoverdine and pyochelin) had the greatest impact on anti-T. cruzi activity. Negative effects on T. cruzi infection by pure pyochelin, but not pyoverdine, or other P. aeruginosa exoproducts studied, were quantitatively similar to the effects of benznidazole, the current standard therapy against T. cruzi. CONCLUSIONS: The P. aeruginosa product pyochelin showed promising activity against T. cruzi and might become a new lead molecule for therapy development.
BACKGROUND: Bacteria are sources of numerous molecules used in treatment of infectious diseases. We investigated effects of molecules produced by 26 Pseudomonas aeruginosa strains against infection of mammalian cell cultures with Trypanosoma cruzi, the aetiological agent of Chagas disease. METHODS: Vero cells were infected with T. cruzi in the presence of wild-type P. aeruginosa supernatants or supernatants of mutants with defects in the production of various virulence, quorum sensing and iron acquisition factors. Quantification of T. cruzi infection (percentage of infected cells) and multiplication (number of amastigotes per infected cell) was performed and cell viability was determined. RESULTS: Wild-type P. aeruginosa products negatively affected T. cruzi infection and multiplication in a dose-dependent manner, without evident toxicity for mammalian cells. PvdD/pchE mutation (loss of the P. aeruginosa siderophores pyoverdine and pyochelin) had the greatest impact on anti-T. cruzi activity. Negative effects on T. cruzi infection by pure pyochelin, but not pyoverdine, or other P. aeruginosa exoproducts studied, were quantitatively similar to the effects of benznidazole, the current standard therapy against T. cruzi. CONCLUSIONS: The P. aeruginosa product pyochelin showed promising activity against T. cruzi and might become a new lead molecule for therapy development.
Authors: Daniel G Lee; Jonathan M Urbach; Gang Wu; Nicole T Liberati; Rhonda L Feinbaum; Sachiko Miyata; Lenard T Diggins; Jianxin He; Maude Saucier; Eric Déziel; Lisa Friedman; Li Li; George Grills; Kate Montgomery; Raju Kucherlapati; Laurence G Rahme; Frederick M Ausubel Journal: Genome Biol Date: 2006-10-12 Impact factor: 13.583
Authors: Bárbara Gionco; Eliandro R Tavares; Admilton G de Oliveira; Sueli F Yamada-Ogatta; Anderson O do Carmo; Ulisses de Pádua Pereira; Roberta T Chideroli; Ane S Simionato; Miguel O P Navarro; Andreas L Chryssafidis; Galdino Andrade Journal: Front Chem Date: 2017-09-15 Impact factor: 5.221