Characterization of alanine catabolism in Pseudomonas aeruginosa and its importance for proliferation in vivo.
The opportunistic pathogen Pseudomonas aeruginosa causes a variety of infections in immunocompromised individuals, including individuals with the heritable disease cystic fibrosis. Like the carbon sources metabolized by many disease-causing bacteria, the carbon sources metabolized by P. aeruginosa at the host infection site are unknown. We recently reported that l-alanine is a preferred carbon source for P. aeruginosa and that two genes potentially involved in alanine catabolism (dadA and dadX) are induced during in vivo growth in the rat peritoneum and during in vitro growth in sputum (mucus) collected from the lungs of individuals with cystic fibrosis. The goals of this study were to characterize factors required for alanine catabolism in P. aeruginosa and to assess the importance of these factors for in vivo growth. Our results reveal that dadA and dadX are arranged in an operon and are required for catabolism of l-alanine. The dad operon is inducible by l-alanine, d-alanine, and l-valine, and induction is dependent on the transcriptional regulator Lrp. Finally, we show that a mutant unable to catabolize dl-alanine displays decreased competitiveness in a rat lung model of infection.
Boulette
Megan L
ML
Section of Molecular Genetics and Microbiology, The University of Texas at Austin, 1 University Station, A5000, Austin, TX 78712, USA.
Baynham
Patricia J
PJ
Jorth
Peter A
PA
Kukavica-Ibrulj
Irena
I
Longoria
Aissa
A
Barrera
Karla
K
Levesque
Roger C
RC
Whiteley
Marvin
M
D000409:Alanine / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D049109:Cell Proliferation; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D010538:Peritonitis / Q000382:microbiology*; D011552:Pseudomonas Infections / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000166:cytology* / Q000378:metabolism*; D051381:Rats; D014158:Transcription, Genetic
D001426:Bacterial Proteins; D000409:Alanine