Presence of the Hmq System and Production of 4-Hydroxy-3-Methyl-2-Alkylquinolines Are Heterogeneously Distributed between Burkholderia cepacia Complex Species and More Prevalent among Environmental than Clinical Isolates

Coulon, Pauline M. L.; Zlosnik, James E. A.; Déziel, Éric

doi:10.1128/spectrum.00127-21

Cited by 4 publications

(4 citation statements)

References 69 publications

(116 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The PQS signal constitutes a highly specific target to address P. aeruginosa because PQS signaling seems to be quite unique for this pathogen. Besides P. aeruginosa , the marine bacterium Pelagibaca bermudensis was reported to produce PQS besides other AQs [ 29 ], while other known AQ producers, such as Burkholderia spp., do not form PQS [ 30 ]. The detection of PQS in sputum, bronchoalveolar lavage, mucopurulent fluid, blood, and urine of P. aeruginosa -infected CF patients [ 31 , 32 , 33 ], as well as necrotic muscle tissue from burn wounds [ 34 ] moreover suggests that AQ-dependent QS is functional during infection.…”

Section: Discussionmentioning

confidence: 99%

Enzyme-Mediated Quenching of the Pseudomonas Quinolone Signal (PQS): A Comparison between Naturally Occurring and Engineered PQS-Cleaving Dioxygenases

et al. 2022

View full text Add to dashboard Cite

The opportunistic pathogen Pseudomonas aeruginosa employs quorum sensing to govern the production of many virulence factors. Interference with quorum sensing signaling has therefore been put forward as an attractive approach to disarm this pathogen. Here, we analyzed the quorum quenching properties of natural and engineered (2-alkyl-)3-hydroxy-4(1H)-quinolone 2,4-dioxygenases (HQDs) that inactivate the P. aeruginosa signal molecule PQS (Pseudomonas quinolone signal; 2-heptyl-3-hydroxy-4(1H)-quinolone). When added exogenously to P. aeruginosa cultures, all HQDs tested significantly reduced the levels of PQS and other alkylquinolone-type secondary metabolites deriving from the biosynthetic pathway, such as the respiratory inhibitor 2-heptyl-4-hydroxyquinoline N-oxide. HQDs from Nocardia farcinica and Streptomyces bingchenggensis, which combine low KM values for PQS with thermal stability and resilience in the presence of P. aeruginosa exoproducts, respectively, attenuated production of the virulence factors pyocyanin and pyoverdine. A delay in mortality was observed when Galleria mellonella larvae were infected with P. aeruginosa suspensions treated with the S. bingchenggensis HQD or with inhibitors of alkylquinolone biosynthesis. Our data indicate that quenching of PQS signaling has potential as an anti-virulence strategy; however, an efficient anti-virulence therapy against P. aeruginosa likely requires a combination of agents addressing multiple targets.

show abstract

Section: Discussionmentioning

confidence: 99%

Enzyme-Mediated Quenching of the Pseudomonas Quinolone Signal (PQS): A Comparison between Naturally Occurring and Engineered PQS-Cleaving Dioxygenases

et al. 2022

View full text Add to dashboard Cite

show abstract

Section: Quorum Sensing (Qs) Signalingmentioning

confidence: 99%

“…Apart from the AHL molecules, BP is known for producing another type of QS molecule known as 4-hydroxy-3-methyl-2-alkylquinolines (HMAQs), which are similar to the Pseudomonas quinolone signal (PQS), 4-hydroxy-2-alkylquinolines (HAQs) that are found in P. aeruginosa [ 73 ]. The PQS molecule is synthesized by the pqsABCDE operon ( pa0996 - pa1000 ) which is homologous to the hhqABCDE ( bpss0481 - bpss0485 ) genes in BP [ 73 - 75 ]. In P. aeruginosa , anthranilic acid is the precursor molecule for the synthesis of HAQs and is supplied by three different pathways that includes anthranilate synthase encoded by phnAB and trpEG and the degradation of tryptophan through the kynurenine pathway [ 75 ].…”

Section: Quorum Sensing (Qs) Signalingmentioning

confidence: 99%

Biofilm Signaling, Composition and Regulation in Burkholderia pseudomallei

Nyanasegran

Nathan

Firdaus-Raih

et al. 2022

J. Microbiol. Biotechnol.

View full text Add to dashboard Cite

The incidence of melioidosis cases caused by the gram-negative pathogen Burkholderia pseudomallei (BP) is seeing an increasing trend that has spread beyond its previously known endemic regions. Biofilms produced by BP have been associated with antimicrobial therapy limitation and relapse melioidosis, thus making it urgently necessary to understand the mechanisms of biofilm formation and their role in BP biology. Microbial cells aggregate and enclose within a self-produced matrix of extracellular polymeric substances (EPSs) to form biofilm. The transition mechanism of bacterial cells from planktonic state to initiate biofilm formation, which involves the formation of surface attachment microcolonies and the maturation of the biofilm matrix, is a dynamic and complex process. Despite the emerging findings on the biofilm formation process, systemic knowledge on the molecular mechanisms of biofilm formation in BP remains fractured. This review provides insights into the signaling systems, matrix composition, and the biosynthesis regulation of EPSs (exopolysaccharide, eDNA and proteins) that facilitate the formation of biofilms in order to present an overview of our current knowledge and the questions that remain regarding BP biofilms.

show abstract

“…[22][23][24][25] The most prominent compounds of this pathway are 2-heptyl-4(1H)-quinolone (HHQ) and 2-heptyl-3-hydroxy-4(1H)-quinolone (commonly referred to as Pseudomonas quinolone signal, PQS), however many naturally occurring variations of these molecules have been isolated from diverse microbes. [25][26][27] To the best of our knowledge, currently characterized AQ degradation/modification pathways begin with the C3-hydroxylated PQS, and result in oxidative ring cleavage, additional C2/C3 oxidation, and/or glucuronidation. [28][29][30][31] To initiate the formation of PQS, which has substantial roles in P. aeruginosa QS, motility, and virulence, the flavin-dependent monooxygenase PqsH catalyzes the regioselective C3 hydroxylation of HHQ.…”

Section: Introductionmentioning

confidence: 99%

Vanadium-dependent haloperoxidases from diverse microbes halogenate exogenous alkyl quinolone quorum sensing signals

Baumgartner,

McCaughey,

Fleming

et al. 2024

Preprint

View full text Add to dashboard Cite

Site-selective vanadium-dependent haloperoxidases (VHPOs) are a unique enzyme family that catalyze selective halogenation reactions previously characterized within bacterial natural product biosynthetic pathways. However, the broader chemical roles and biological distribution of these halogenases remains to be explored. Using bioinformatic methods, we have defined a VHPO subfamily that regioselectively brominates alkyl quinolone (AQ) quorum sensing molecules.In vitroAQ halogenation activity was demonstrated from phylogenetically distinct bacteria lacking established AQ biosynthetic pathways and sourced from diverse environments. AQ-VHPOs show high sequence and biochemical similarities with negligible genomic synteny or biosynthetic gene cluster co-localization. Exposure of VHPO-containing microbes to synthetic AQs or established bacterial producers identifies the chemical and spatial response to subvert their bacteriostatic effects. The characterization of novel homologs from bacterial taxa without previously demonstrated vanadium enzymology suggests VHPO-mediated AQ bromination is a niche to manipulate the chemical ecology of microbial communities.Table of Contents GraphicSynopsisA broadly distributed subfamily of bacterial site-selective VHPOs provides protection against exogenously encountered bacteriostatic alkyl quinolone quorum sensing signals.

show abstract

Presence of the Hmq System and Production of 4-Hydroxy-3-Methyl-2-Alkylquinolines Are Heterogeneously Distributed between Burkholderia cepacia Complex Species and More Prevalent among Environmental than Clinical Isolates

Cited by 4 publications

References 69 publications

Enzyme-Mediated Quenching of the Pseudomonas Quinolone Signal (PQS): A Comparison between Naturally Occurring and Engineered PQS-Cleaving Dioxygenases

Enzyme-Mediated Quenching of the Pseudomonas Quinolone Signal (PQS): A Comparison between Naturally Occurring and Engineered PQS-Cleaving Dioxygenases

Biofilm Signaling, Composition and Regulation in Burkholderia pseudomallei

Vanadium-dependent haloperoxidases from diverse microbes halogenate exogenous alkyl quinolone quorum sensing signals

Contact Info

Product

Resources

About