1887

Abstract

Chronic lung infections caused by are the leading cause of morbidity and mortality for cystic fibrosis (CF) patients. Adaptation of to the CF lung results in the loss of acute virulence determinants and appears to activate chronic virulence strategies in this pathogen. In order to identify such strategies, a random transposon mutagenesis was performed and 18 genes that were required for optimal infection of alfalfa seedlings by FRD1, a CF isolate of , were recognized. The largest subset of genes (seven of the 18), were associated with central carbon metabolism, including the gene that encodes isocitrate lyase (ICL), . Because FRD1 is avirulent in animal infection models, we constructed an ICL mutant in strain PAO1 in order to assess the requirement of ICL in mammalian infection. The PAO1 ICL mutant was less virulent in the rat lung infection model, indicating that ICL is required for the pathogenesis of in mammals. Furthermore, FRD1 showed increased ICL activity and expression of an  : :  fusion compared to PAO1. We suggest that upregulation of ICL occurred during adaptation of FRD1 to the CF lung and that some of the novel virulence mechanisms employed by FRD1 to infect alfalfa seedlings may be the same mechanisms relies upon to persist within human niches.

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2008-06-01
2019-10-18
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