The transcriptional regulator AlgR controls cyanide production in Pseudomonas aeruginosa.
Pseudomonas aeruginosa is an opportunistic pathogen that causes chronic lung infections in cystic fibrosis (CF) patients. One characteristic of P. aeruginosa CF isolates is the overproduction of the exopolysaccharide alginate, controlled by AlgR. Transcriptional profiling analyses comparing mucoid P. aeruginosa strains to their isogenic algR deletion strains showed that the transcription of cyanide-synthesizing genes (hcnAB) was approximately 3-fold lower in the algR mutants. S1 nuclease protection assays corroborated these findings, indicating that AlgR activates hcnA transcription in mucoid P. aeruginosa. Quantification of hydrogen cyanide (HCN) production from laboratory isolates revealed that mucoid laboratory strains made sevenfold more HCN than their nonmucoid parental strains. In addition, comparison of laboratory and clinically derived nonmucoid strains revealed that HCN was fivefold higher in the nonmucoid CF isolates. Moreover, the average amount of cyanide produced by mucoid clinical isolates was 4.7 +/- 0.85 micromol of HCN/mg of protein versus 2.4 +/- 0.40 micromol of HCN/mg of protein for nonmucoid strains from a survey conducted with 41 P. aeruginosa CF isolates from 24 patients. Our data indicate that (i) mucoid P. aeruginosa regardless of their origin (laboratory or clinically derived) produce more cyanide than their nonmucoid counterparts, (ii) AlgR regulates HCN production in P. aeruginosa, and (iii) P. aeruginosa CF isolates are more hypercyanogenic than nonmucoid laboratory strains. Taken together, cyanide production may be a relevant virulence factor in CF lung disease, the production of which is regulated, in part, by AlgR.
Department of Microbiology and Immunology, Tulane University Health Sciences Center, 1430 Tulane Ave., New Orleans, LA 70112-2699, USA.
Alexander J
AJ
Carterson
Lisa A
LA
Morici
Debra W
DW
Jackson
Anders
A
Frisk
Stephen E
SE
Lizewski
Ryan
R
Jupiter
Kendra
K
Simpson
Daniel A
DA
Kunz
Scott H
SH
Davis
Jill R
JR
Schurr
Daniel J
DJ
Hassett
Michael J
MJ
Schurr
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D003470:Culture Media; D003550:Cystic Fibrosis / Q000382:microbiology*; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D006856:Hydrogen Cyanide / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D050891:Oxidoreductases Acting on CH-NH2 Group Donors; D011401:Promoter Regions, Genetic; D011552:Pseudomonas Infections / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
C110681:AlgR protein, Pseudomonas aeruginosa; D001426:Bacterial Proteins; D003470:Culture Media; D009097:Multienzyme Complexes; D015534:Trans-Activators; D006856:Hydrogen Cyanide; D010088:Oxidoreductases; D050891:Oxidoreductases Acting on CH-NH2 Group Donors; C112800:glycine dehydrogenase (cyanide-forming)