Pseudomonas aeruginosa DesB Promotes Staphylococcus aureus Growth Inhibition in Coculture by Controlling the Synthesis of HAQs

Pseudomonas aeruginosa is a pathogen that can cause serious infections and usually coexists with other pathogens, such as Staphylococcus aureus . Virulence factors are important for maintaining a presence of the organisms in these multispecies environments, and DesB plays an important role in P . aeruginosa virulence. Therefore, we investigated the effect of DesB on S . aureus reduction under competitive situation. Liquid cultures of P . aeruginosa wild type (WT) and its desB mutant were spotted on agar plates containing S . aureus , and the size of the clear zones was compared. In addition, interbacterial competition between P . aeruginosa and S . aureus was observed over time during planktonic coculture. The transcriptional profiles of the WT and desB mutant were compared by qRT-PCR and microarray to determine the role of DesB in S . aureus reduction at the molecular level. As a result, the clear zone was smaller for the desB mutant than for P . aeruginosa PAO1 (WT), and in planktonic coculture, the number of S . aureus cells was reduced in the desB mutant. qRT-PCR and microarray revealed that the expression of MvfR-controlled pqsA-E and phnAB operons was significantly decreased, but the mexEF-oprN operon was highly expressed. The results indicate that intracellular levels of 4-hydroxy-2-heptylquinoline (HHQ), a ligand of MvfR, are reduced due to MexEF-OprN-mediated efflux in desB mutant, resulting in the decrease of MvfR binding to pqsA-E promoter and the reduction of 4-hydroxy-2-alkylquinolines (HAQs) synthesis. Overexpression of mexEF-oprN operon in desB mutant was phenotypically confirmed by observing significantly increased resistance to chloramphenicol. In conclusion, these results suggest that DesB plays a role in the inhibition of S . aureus growth by controlling HAQ synthesis.