Non-mucoid reversion of mucoid pseudomonas aeruginosa induced by sulfate-stimulated growth

Abstract

Alginate overproducing mucoid Pseudomonas aeruginosa, responsible for chronic airway infections in cystic fibrosis (CF) patients, is resistant to antibiotic treatments and host immune clearance. In this study, we performed a Phenotype Microarray screen and identified sulfate ion as a molecule that can suppress alginate production. When a mucoid P. aeruginosa strain CM21 and additional mucoid isolates were grown with 5% sodium sulfate, significantly decreased levels of alginate were produced. Suppression of alginate production was also induced by other sulfate salts. Expression of a reporter gene fused to algD promoter was considerably decreased when grown with sulfate. Furthermore, bacterial cell shape was abnormally altered in CM21, but not in PAO1, a prototype non-mucoid strain suggesting that sulfate-stimulated cell shape change is associated with transcriptional suppression of the alginate operon. Finally, a CM21 lpxC mutant defective in lipid A biosynthesis continued to produce alginate and maintained the correct cell shape when grown with sulfate. These results suggest a potential involvement of LPS biosynthesis in the sulfate-induced reversion to non-mucoid phenotype. Together, this study proposes a novel strategy that can be potentially applied to treat persistent infection by recalcitrant mucoid P. aeruginosa.