The stringent response is a mechanism by which bacteria adapt to
nutritional deficiencies through the production of the
guanine nucleotides ppGpp and pppGpp, produced by the
RelA enzyme. We investigated the role of the relA gene in the ability of an extracellular pathogen, Pseudomonas aeruginosa, to cause
infection. Strains lacking the relA gene were created from the prototypical laboratory strain PAO1 as well as the mucoid
cystic fibrosis isolate 6106, which lacks functional quorum-sensing systems. The absence of relA abolished the production of
ppGpp and pppGpp under conditions of
amino acid starvation. We found that strains lacking relA exhibited reduced virulence in a D. melanogaster feeding assay. In conditions of low
magnesium, the relA gene enhanced production of the cell-cell signal N-[3-oxododecanoyl]-l-
homoserine lactone, whereas relA reduced the production of the
2-heptyl-3-hydroxy-4-quinolone signal during
serine hydroxamate induction of the stringent response. In the relA mutant, alterations in the Pseudomonas
quinolone system pathways seemed to increase the production of
pyocyanin and decrease the production of
elastase. Deletion of relA also resulted in reduced levels of the RpoS
sigma factor. These results suggest that adjustment of cellular
ppGpp and pppGpp levels could be an important regulatory mechanism in P. aeruginosa adaptation in pathogenic relationships.