Biotic inactivation of the P seudomonas aeruginosa quinolone signal molecule

Summary In P seudomonas aeruginosa , quorum sensing ( QS ) regulates the production of secondary metabolites, many of which are antimicrobials that impact on polymicrobial community composition. Consequently, quenching QS modulates the environmental impact of P . aeruginosa . To identify bacteria capable of inactivating the QS signal molecule 2‐heptyl‐3‐hydroxy‐4(1 H )‐quinolone ( PQS ), a minimal medium containing PQS as the sole carbon source was used to enrich a M alaysian rainforest soil sample. This yielded an A chromobacter xylosoxidans strain ( Q 19) that inactivated PQS , yielding a new fluorescent compound ( I ‐ PQS ) confirmed as PQS ‐derived using deuterated PQS . The I ‐ PQS structure was elucidated using mass spectrometry and nuclear magnetic resonance spectroscopy as 2‐heptyl‐2‐hydroxy‐1,2‐dihydroquinoline‐3,4‐dione ( HHQD ). A chromobacter xylosoxidans   Q 19 oxidized PQS congeners with alkyl chains ranging from C 1 to C 5 and also N ‐methyl PQS , yielding the corresponding 2‐hydroxy‐1,2‐dihydroquinoline‐3,4‐diones, but was unable to inactivate the PQS precursor HHQ . This indicates that the hydroxyl group at position 3 in PQS is essential and that A . xylosoxidans inactivates PQS via a pathway involving the incorporation of oxygen at C 2 of the heterocyclic ring. The conversion of PQS to HHQD also occurred on incubation with 12/17 A . xylosoxidans strains recovered from cystic fibrosis patients, with P . aeruginosa and with A rthrobacter , suggesting that formation of hydroxylated PQS may be a common mechanism of inactivation.