Human targets of Pseudomonas aeruginosa pyocyanin
- PMID: 14605211
- PMCID: PMC283589
- DOI: 10.1073/pnas.2332354100
Human targets of Pseudomonas aeruginosa pyocyanin
Abstract
Pseudomonas aeruginosa produces copious amounts of the redoxactive tricyclic compound pyocyanin that kills competing microbes and mammalian cells, especially during cystic fibrosis lung infection. Cross-phylum susceptibility to pyocyanin suggests the existence of evolutionarily conserved physiological targets. We screened a Saccharomyces cerevisiae deletion library to identify presumptive pyocyanin targets with the expectation that similar targets would be conserved in humans. Fifty S. cerevisiae targets were provisionally identified, of which 60% have orthologous human counterparts. These targets encompassed major cellular pathways involved in the cell cycle, electron transport and respiration, epidermal cell growth, protein sorting, vesicle transport, and the vacuolar ATPase. Using cultured human lung epithelial cells, we showed that pyocyanin-mediated reactive oxygen intermediates inactivate human vacuolar ATPase, supporting the validity of the yeast screen. We discuss how the inactivation of V-ATPase may negatively impact the lung function of cystic fibrosis patients.
Figures





Similar articles
-
Pseudomonas aeruginosa pyocyanin inactivates lung epithelial vacuolar ATPase-dependent cystic fibrosis transmembrane conductance regulator expression and localization.Cell Microbiol. 2006 Jul;8(7):1121-33. doi: 10.1111/j.1462-5822.2006.00696.x. Cell Microbiol. 2006. PMID: 16819965
-
Genome-wide identification of genes required for yeast growth under imatinib stress: vacuolar H+-ATPase function is an important target of this anticancer drug.OMICS. 2009 Jun;13(3):185-98. doi: 10.1089/omi.2008.0086. OMICS. 2009. PMID: 19260806
-
Pseudomonas aeruginosa pyocyanin is critical for lung infection in mice.Infect Immun. 2004 Jul;72(7):4275-8. doi: 10.1128/IAI.72.7.4275-4278.2004. Infect Immun. 2004. PMID: 15213173 Free PMC article.
-
The role of pyocyanin in Pseudomonas aeruginosa infection.Trends Mol Med. 2004 Dec;10(12):599-606. doi: 10.1016/j.molmed.2004.10.002. Trends Mol Med. 2004. PMID: 15567330 Review.
-
V-ATPase, ScNhx1p and yeast vacuole fusion.J Genet Genomics. 2012 Apr 20;39(4):167-71. doi: 10.1016/j.jgg.2012.02.001. Epub 2012 Feb 10. J Genet Genomics. 2012. PMID: 22546538 Review.
Cited by
-
The multiple signaling systems regulating virulence in Pseudomonas aeruginosa.Microbiol Mol Biol Rev. 2012 Mar;76(1):46-65. doi: 10.1128/MMBR.05007-11. Microbiol Mol Biol Rev. 2012. PMID: 22390972 Free PMC article. Review.
-
A cytotoxic type III secretion effector of Vibrio parahaemolyticus targets vacuolar H+-ATPase subunit c and ruptures host cell lysosomes.PLoS Pathog. 2012;8(7):e1002803. doi: 10.1371/journal.ppat.1002803. Epub 2012 Jul 19. PLoS Pathog. 2012. PMID: 22829766 Free PMC article.
-
Pyocyanin alters redox homeostasis and carbon flux through central metabolic pathways in Pseudomonas aeruginosa PA14.J Bacteriol. 2007 Sep;189(17):6372-81. doi: 10.1128/JB.00505-07. Epub 2007 May 25. J Bacteriol. 2007. PMID: 17526704 Free PMC article.
-
Inactivation of FOXA2 by Respiratory Bacterial Pathogens and Dysregulation of Pulmonary Mucus Homeostasis.Front Immunol. 2020 Mar 25;11:515. doi: 10.3389/fimmu.2020.00515. eCollection 2020. Front Immunol. 2020. PMID: 32269574 Free PMC article. Review.
-
The power of chemical genomics to study the link between endomembrane system components and the gravitropic response.Proc Natl Acad Sci U S A. 2005 Mar 29;102(13):4902-7. doi: 10.1073/pnas.0500222102. Epub 2005 Mar 16. Proc Natl Acad Sci U S A. 2005. PMID: 15772170 Free PMC article.
References
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases