Acyl Carrier Protein 3 Is Involved in Oxidative Stress Response in Pseudomonas aeruginosa

The human opportunistic pathogen Pseudomonas aeruginosa expresses three acyl carrier proteins (ACPs): AcpP, Acp1, and Acp3. The function of AcpP in membrane fatty acid synthesis (FAS) was confirmed recently, but the physiological roles of Acp1 and Acp3 remain unclear. To address this, we investigated the physiological role of Acp3 in P. aeruginosa. We found that expression of Acp3 dramatically increases in the log phase of cell growth and that its transcription is under the control of the QS regulators LasR and RhlR. Deletion of acp3 from P. aeruginosa strain PAO1 results in thicker biofilm formation, increased resistance of the strain to hydrogen peroxide, and higher persistence in a mouse infection model. Tandem affinity purification (TAP) experiments revealed several novel protein-binding partners of Acp3, including KatA, the major catalase in P. aeruginosa. Acp3 was found to repress the catalase activity of KatA and, consistent with inhibition by Acp3, less reactive oxygen species are present in the acp3 deletion strain. Overall, our study reveals that Acp3 has a distinct function from that of the canonical AcpP and may be involved in the oxidative stress response

The role of 2,4-dihydroxyquinoline (DHQ) in Pseudomonas aeruginosa pathogenicity

Bacteria synchronize group behaviors using quorum sensing, which is advantageous during an infection to thwart immune cell attack and resist deleterious changes in the environment. In Pseudomonas aeruginosa, the Pseudomonas quinolone signal (Pqs) quorum-sensing system is an important component of an interconnected intercellular communication network. Two alkylquinolones, 2-heptyl-4-quinolone (HHQ) and 2-heptyl-3-hydroxy-4-quinolone (PQS), activate transcriptional regulator PqsR to promote the production of quinolone signals and virulence factors. Our work focused on the most abundant quinolone produced from the Pqs system, 2,4-dihydroxyquinoline (DHQ), which was shown previously to sustain pyocyanin production and antifungal activity of P. aeruginosa. However, little is known about how DHQ affects P. aeruginosa pathogenicity. Using C. elegans as a model for P. aeruginosa infection, we found pqs mutants only able to produce DHQ maintained virulence towards the nematodes similar to wild-type. In addition, DHQ-only producing mutants displayed increased colonization of C. elegans and virulence factor production compared to a quinolone-null strain. DHQ also bound to PqsR and activated the transcription of pqs operon. More importantly, high extracellular concentration of DHQ was maintained in both aerobic and anaerobic growth. High levels of DHQ were also detected in the sputum samples of cystic fibrosis patients. Taken together, our findings suggest DHQ may play an important role in sustaining P. aeruginosa pathogenicity under oxygen-limiting conditions