Virulence determinants from a cystic fibrosis isolate of Pseudomonas aeruginosa include isocitrate lyase.
Chronic lung infections caused by Pseudomonas aeruginosa are the leading cause of morbidity and mortality for cystic fibrosis (CF) patients. Adaptation of P. aeruginosa 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 P. aeruginosa, 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), aceA. Because FRD1 is avirulent in animal infection models, we constructed an ICL mutant in P. aeruginosa 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 P. aeruginosa in mammals. Furthermore, FRD1 showed increased ICL activity and expression of an aceA : : lacZ 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 P. aeruginosa relies upon to persist within human niches.
Department of Biological Sciences, Auburn University, AL 36849, USA.
Tamishia L
TL
Lindsey
Department of Biological Sciences, Auburn University, AL 36849, USA.
Jessica M
JM
Hagins
Department of Microbiology and Infectious Diseases, University of Calgary Health Sciences Centre, Calgary, AB T2N 4N1, Canada.
Pamela A
PA
Sokol
Department of Biological Sciences, Auburn University, AL 36849, USA.
Laura A
LA
Silo-Suh
D000818:Animals; D018441:Biofilms / Q000254:growth & development; D003550:Cystic Fibrosis / Q000150:complications / Q000382:microbiology*; D004251:DNA Transposable Elements / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D007522:Isocitrate Lyase / Q000235:genetics / Q000378:metabolism*; D008297:Male; D016254:Mutagenesis, Insertional; D011552:Pseudomonas Infections / Q000150:complications / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000201:enzymology* / Q000302:isolation & purification / Q000472:pathogenicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation; D014774:Virulence / Q000235:genetics
D004251:DNA Transposable Elements; D007522:Isocitrate Lyase