Biotic inactivation of the Pseudomonas aeruginosa quinolone signal molecule

In Pseudomonas 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(1H)-quinolone (PQS), a minimal medium containing PQS as the sole carbon source was used to enrich a Malaysian rainforest soil sample. This yielded an Achromobacter xylosoxidans strain (Q19) 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). Achromobacter xylosoxidans Q19 oxidized PQS congeners with alkyl chains ranging from C1 to C5 and also N-methyl PQS, yielding the corresponding 2-hydroxy-1,2-dihydroquinoline-3,4- diones, but was unable to inactivate thePQSprecursor 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 C2 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 Arthrobacter, suggesting that formation of hydroxylated PQS may be a common mechanism of inactivation

Biotic inactivation of the Pseudomonas aeruginosa quinolone signal molecule

In Pseudomonas 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(1H)-quinolone (PQS), a minimal medium containing PQS as the sole carbon source was used to enrich a Malaysian rainforest soil sample. This yielded an Achromobacter xylosoxidans strain (Q19) 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). Achromobacter xylosoxidans Q19 oxidized PQS congeners with alkyl chains ranging from C1 to C5 and also N-methyl PQS, yielding the corresponding 2-hydroxy-1,2-dihydroquinoline-3,4- diones, but was unable to inactivate thePQSprecursor 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 C2 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 Arthrobacter, suggesting that formation of hydroxylated PQS may be a common mechanism of inactivation

Rhodococcus erythropolis BG43 genes mediating Pseudomonas aeruginosa quinolone signal degradation and virulence factor attenuation

Müller C, Birmes FS, Rückert C, Kalinowski J, Fetzner S. Rhodococcus erythropolis BG43 genes mediating Pseudomonas aeruginosa quinolone signal degradation and virulence factor attenuation. Applied and Environmental Microbiology. 2015;81(22):7720-7729

Complete genome sequence of Rhodococcus erythropolis BG43 (DSM 46869), a degrader of Pseudomonas aeruginosa quorum sensing signal molecules

Rückert C, Birmes FS, Müller C, et al. Complete genome sequence of Rhodococcus erythropolis BG43 (DSM 46869), a degrader of Pseudomonas aeruginosa quorum sensing signal molecules. Journal of biotechnology. 2015;211:99-100.: Rhodococcus erythropolis BG43 was isolated from soil and characterized as a degrader of the quorum sensing signal molecules 2-heptyl-3-hydroxy-4(1H)-quinolone (the Pseudomonas quinolone signal, PQS) and 2-heptyl-4(1H)-quinolone, produced by Pseudomonas aeruginosa. The complete genome of R. erythropolis BG43 consists of a circular chromosome and three plasmids, one of them circular and two linear ones. In total, 6158 protein-coding regions were identified. With this genome sequence, the genetic basis of its quorum-quenching ability and possible biotechnological applications can be explored further

Chemical Modification and Detoxification of the <i>Pseudomonas aeruginosa</i> Toxin 2‑Heptyl-4-hydroxyquinoline <i>N</i>‑Oxide by Environmental and Pathogenic Bacteria

2-Heptyl-4-hydroxyquinoline <i>N</i>-oxide (HQNO), a major secondary metabolite and virulence factor produced by the opportunistic pathogen <i>Pseudomonas aeruginosa</i>, acts as a potent inhibitor of respiratory electron transfer and thereby affects host cells as well as microorganisms. In this study, we demonstrate the previously unknown capability of environmental and pathogenic bacteria to transform and detoxify this compound. Strains of <i>Arthrobacter</i> and <i>Rhodococcus</i> spp. as well as <i>Staphylococcus aureus</i> introduced a hydroxyl group at C-3 of HQNO, whereas <i>Mycobacterium abscessus</i>, <i>M. fortuitum</i>, and <i>M. smegmatis</i> performed an <i>O</i>-methylation, forming 2-heptyl-1-methoxy-4-oxoquinoline as the initial metabolite. <i>Bacillus</i> spp. produced the glycosylated derivative 2-heptyl-1-(β-d-glucopyranosydyl)-4-oxoquinoline. Assaying the effects of these metabolites on cellular respiration and on quinol oxidase activity of membrane fractions revealed that their EC₅₀ values were up to 2 orders of magnitude higher than that of HQNO. Furthermore, cellular levels of reactive oxygen species were significantly lower in the presence of the metabolites than under the influence of HQNO. Therefore, the capacity to transform HQNO should lead to a competitive advantage against <i>P. aeruginosa.</i> Our findings contribute new insight into the metabolic diversity of bacteria and add another layer of complexity to the metabolic interactions which likely contribute to shaping polymicrobial communities comprising <i>P. aeruginosa.</i