Towards Understanding Pseudomonas aeruginosa Infection through Global Expression Profiling: From Models to Real Infection Settings and Proposed Prevention Strategies

Abstract

Pseudomonas aeruginosa is a threatening opportunistic pathogen that causes severe acute and chronic infections in immunocompromised patients. Global transcriptomic analysis of P. aeruginosa infecting various hosts was carried out. In vivo gene expression was successfully performed by developing accurate, specific technical procedures. The transcriptomic analysis suggested that the main factors expressed by P. aeruginosa upon infection of burn wounds are iron and zinc acquisition as well as alginate production. The bacterial state during burn wound infection was not fully acute, with bacterial cells undergoing serious iron limitation and having a slower metabolism. Iron acquisition and alginate production were shown to be important mechanisms common among the infection conditions studied, namely burn wound, CF patient and mouse tumour model. Two models for P. aeruginosa infection were tested. The tumour mouse model is a promising mammalian infection model whereby P. aeruginosa exhibits anaerobic growth, biofilm formation and expresses the type III secretion system. This model is being further tested in order to assess if it can be used as a chronic infection model. The plant infection model using lettuce leaves may be useful for the study of certain factors such as QS systems, but yielded different results as compared to the real mammalian infections and cannot therefore be used as a reliable infection model. The analysis of the gene expression data from the work presented here thus provided a wealth of new insights and established a foundation for future work directed at the understanding of P. aeruginosa infection and at finding new prevention and treatment strategies.