Enzyme-Mediated Quenching of the Quinolone Signal (PQS) Promotes Biofilm Formation of by Increasing Iron Availability.

The 2-alkyl-3-hydroxy-4(1)-quinolone 2,4-dioxygenase HodC was previously described to cleave the quinolone signal, PQS, which is exclusively used in the complex quorum sensing (QS) system of , an opportunistic pathogen employing QS to regulate virulence and biofilm development. Degradation of PQS by exogenous addition of HodC to planktonic cells of attenuated production of virulence factors, and reduced virulence . However, proteolytic cleavage reduced the efficacy of HodC. Here, we identified the secreted protease LasB of to be responsible for HodC degradation. In static biofilms of the PA14 ::Tn mutant, the catalytic activity of HodC led to an increase in viable biomass in newly formed but also in established biofilms, and reduced the expression of genes involved in iron metabolism and siderophore production, such as , and . This is likely due to an increase in the levels of bioavailable iron by degradation of PQS, which is able to sequester iron from the surrounding environment. Thus, HodC, despite its ability to quench the production of virulence factors, is contraindicated for combating biofilms.