Carbapenem antibiotic production in Erwinia carotovora is regulated by CarR, a homologue of the LuxR transcriptional activator

McGowan, Simon J.; Sebaihia, Mohammed; Jones, Susan; Yu, Bo; Bainton, Nigel J.; Chan, Pan F.; Bycroft, Barrie W.; Stewart, Gordon S. A. B.; Williams, Paul; Salmond, George P. C.

doi:10.1099/13500872-141-3-541

Cited by 163 publications

(111 citation statements)

References 39 publications

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“…It is not uncommon for QS to control production of secondary metabolites. Examples include carbapenem production by Erwinia carotovora (44)(45)(46), phenazine production by Pseudomonas chloroaphis (47), violacein by Chromobacterium violaceum (48), bactobolin by B. thailandensis (8,25), mupirocin by Pseudomonas fluorescens (49), and rhamnolipids, pyocyanin, hydrogen cyanide, and pyoverdin by P. aeruginosa (50)(51)(52)(53). Control of secondary metabolite genes by QS in B. thailandensis is complex.…”

Section: Discussionmentioning

confidence: 99%

Global Analysis of the Burkholderia thailandensis Quorum Sensing-Controlled Regulon

et al. 2014

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c Burkholderia thailandensis contains three acyl-homoserine lactone quorum sensing circuits and has two additional LuxR homologs. To identify B. thailandensis quorum sensing-controlled genes, we carried out transcriptome sequencing (RNA-seq) analyses of quorum sensing mutants and their parent. The analyses were grounded in the fact that we identified genes coding for factors shown previously to be regulated by quorum sensing among a larger set of quorum-controlled genes. We also found that genes coding for contact-dependent inhibition were induced by quorum sensing and confirmed that specific quorum sensing mutants had a contact-dependent inhibition defect. Additional quorum-controlled genes included those for the production of numerous secondary metabolites, an uncharacterized exopolysaccharide, and a predicted chitin-binding protein. This study provides insights into the roles of the three quorum sensing circuits in the saprophytic lifestyle of B. thailandensis, and it provides a foundation on which to build an understanding of the roles of quorum sensing in the biology of B. thailandensis and the closely related pathogenic Burkholderia pseudomallei and Burkholderia mallei.

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Section: Discussionmentioning

confidence: 99%

Global Analysis of the Burkholderia thailandensis Quorum Sensing-Controlled Regulon

et al. 2014

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“…LuxR is a transcriptional activator that requires the AHL coinducer to initiate the expression of the lux-encoded functions (3). Analogous AHL-dependent activation mechanisms govern Ti plasmid conjugal transfer in Agrobacterium tumefaciens (10), the expression of virulence factors in Pseudomonas aeruginosa (11), the induction of antibiotic biosynthesis in P. aureofaciens (12) and Erwinia carotovora (13), exoenzyme synthesis in E. carotovora (14), and the expression of functions important in root nodulation and growth inhibition in Rhizobium leguminosarum (15). Additional bacterial quorum-sensing mechanisms are described in other recent reviews (1-4, 16, 17).…”

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confidence: 99%

A negative regulator mediates quorum-sensing control of exopolysaccharide production in Pantoea stewartii subsp. stewartii

Bodman

Majerczak²,

Coplin³

1998

Proc. Natl. Acad. Sci. U.S.A.

237

227

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Classical quorum-sensing (autoinduction) regulation, as exemplified by the lux system of Vibrio fischeri, requires N-acyl homoserine lactone (AHL) signals to stimulate cognate transcriptional activators for the cell densitydependent expression of specific target gene systems. For Pantoea stewartii subsp. stewartii, a bacterial pathogen of sweet corn and maize, the extracellular polysaccharide (EPS) stewartan is a major virulence factor, and its production is controlled by quorum sensing in a population densitydependent manner. Two genes, esaI and esaR, encode essential regulatory proteins for quorum sensing. EsaI is the AHL signal synthase, and EsaR is the cognate gene regulator. esaI, ⌬esaR, and ⌬esaI-esaR mutations were constructed to establish the regulatory role of EsaR. We report here that strains containing an esaR mutation produce high levels of EPS independently of cell density and in the absence of the AHL signal. Our data indicate that quorum-sensing regulation in P. s. subsp. stewartii, in contrast to most other described systems, uses EsaR to repress EPS synthesis at low cell density, and that derepression requires micromolar amounts of AHL. In addition, derepressed esaR strains, which synthesize EPS constitutively at low cell densities, were significantly less virulent than the wild-type parent. This finding suggests that quorum sensing in P. s. subsp. stewartii may be a mechanism to delay the expression of EPS during the early stages of infection so that it does not interfere with other mechanisms of pathogenesis.

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“…Although this compound is not a medicinally useful carbapenem due to its lack of a C-6 side chain, it nonetheless shares an identical nucleus with carbapenems that are (4). Eight of the genes, carA-H, are organized as an operon controlled by CarR, an LuxR type transcriptional activator (9,10). Five of the genes, carA-E, are believed to be directly involved in the production of the (5R)-carbapenem nucleus, and it has been shown that it can be produced in Escherichia coli, albeit at lower levels, using only CarA-C (11,12).…”

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confidence: 99%

Crystal Structure of Carbapenem Synthase (CarC)

Clifton¹,

Doan²,

Sleeman³

et al. 2003

Journal of Biological Chemistry

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The proposed biosynthetic pathway to the carbapenem antibiotics proceeds via epimerization/desaturation of a carbapenam in an unusual process catalyzed by an iron-and 2-oxoglutarate-dependent oxygenase, CarC. Crystal structures of CarC complexed with Fe(II) and 2-oxoglutarate reveal it to be hexameric (space group C222 1 ), consistent with solution studies. CarC monomers contain a double-stranded ␤-helix core that supports ligands binding a single Fe(II) to which 2-oxoglutarate complexes in a bi-dentate manner. A structure was obtained with L-N-acetylproline acting as a substrate analogue. Quantum mechanical/molecular mechanical modeling studies with stereoisomers of carbapenams and carbapenems were used to investigate substrate binding. The combined work will stimulate further mechanistic studies and aid in the engineering of carbapenem biosynthesis.

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Carbapenem antibiotic production in Erwinia carotovora is regulated by CarR, a homologue of the LuxR transcriptional activator

Cited by 163 publications

References 39 publications

Global Analysis of the Burkholderia thailandensis Quorum Sensing-Controlled Regulon

Global Analysis of the Burkholderia thailandensis Quorum Sensing-Controlled Regulon

A negative regulator mediates quorum-sensing control of exopolysaccharide production in Pantoea stewartii subsp. stewartii

Crystal Structure of Carbapenem Synthase (CarC)

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