Regulatory circuits and communication in Gram-negative bacteria

Lazdunski, Andrée; Ventre, Isabelle; Sturgis, James N.

doi:10.1038/nrmicro924

Cited by 203 publications

(178 citation statements)

References 120 publications

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“…The C terminus of SHJG8833 contains a helix-turn-helix (HTH) DNA-binding domain (amino acids 864-918) of LuxR family regulatory proteins (Fig. 2a), which is mainly involved in the binding of the promoter sequence upstream of its target gene (Chen & Xie, 2011;Lazdunski et al, 2004). Apparently, SHJG8833 is a member of the large ATP-binding regulators of the LuxR family (LAL).…”

Section: Sequence Analysis Of Shjg8833 Shjg8837 and Shjg8838mentioning

confidence: 99%

Regulation of the biosynthesis of thiopeptide antibiotic cyclothiazomycin by the transcriptional regulator SHJG8833 in Streptomyces hygroscopicus 5008

Zhang

Chen

et al. 2014

Microbiology

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Cyclothiazomycin is a member of the thiopeptide antibiotics, which are usually complicated derivatives of ribosomally synthesized peptides. A gene cluster containing 12 ORFs identical to the clt cluster encoding cyclothiazomycin from Streptomyces hygroscopicus 10-22 was revealed by genome sequencing in S. hygroscopicus 5008. Genes SHJG8833 and SHJG8837 of the cluster and flanking gene SHJG8838 were predicted to encode regulatory proteins from different families. In this study, we showed that the newly identified cluster is functional and we investigated the roles of these regulatory genes in the regulation of cyclothiazomycin biosynthesis. We determined that SHJG8833, but not SHJG8837 or SHJG8838, is critical for cyclothiazomycin biosynthesis. The transcriptional start point of SHJG8833 was located to a thymidine 54 nt upstream of the start codon. Inactivation of SHJG8833 abrogated the production of cyclothiazomycin, and synthesis could be restored by reintroducing SHJG8833 into the mutant strain. Gene expression analyses indicated that SHJG8833 regulates a consecutive set of seven genes from SHJG8826 to SHJG8832, whose products are predicted to be involved in different steps in the construction of the main framework of cyclothiazomycin. Transcriptional analysis indicated that these seven genes may form two operons, SHJG8826-27 and SHJG8828-32. Gel-shift analysis demonstrated that the DNA-binding domain of SHJG8833 binds the promoters of SHJG8826 and SHJG8828 and sequences internal to SHJG8826 and SHJG8829, and a conserved binding sequence was deduced. These results indicate that SHJG8833 is a positive regulator that controls cyclothiazomycin biosynthesis by activating structural genes in the clt cluster.

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Section: Sequence Analysis Of Shjg8833 Shjg8837 and Shjg8838mentioning

confidence: 99%

Regulation of the biosynthesis of thiopeptide antibiotic cyclothiazomycin by the transcriptional regulator SHJG8833 in Streptomyces hygroscopicus 5008

Zhang

Chen

et al. 2014

Microbiology

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“…The latter facilitate the coordination of gene expression within a bacterial population [1][2][3][4] . Cell-to-cell communication in bacteria is referred to as ''quorum sensing'' (QS) and depends on the action of diffusible signal molecules or ''autoinducers'' .…”

Section: Introductionmentioning

confidence: 99%

Biosensor-based assays for PQS, HHQ and related 2-alkyl-4-quinolone quorum sensing signal molecules

et al. 2007

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2-Alkyl-4-quinolones (AHQs) such as 2-heptyl-3-hydroxy-4-quinolone (PQS) and 2-heptyl-4-quinolone (HHQ) are quorum sensing signal molecules. Here, we describe methods for AHQ detection, tentative identification and quantification, which employ a lux-based Pseudomonas aeruginosa AHQ biosensor strain. The protocol describes both thin-layer chromatography (TLC) and microtiter plate assays, which use bioluminescence or the green color of pyocyanin as detection end points. Organic solvent extracts of bacterial cells or cell-free culture supernatants are chromatographed on TLC plates, which are dried and overlaid with the AHQ biosensor. AHQs appear as both luminescent and green spots. For the microtiter assay, either spent bacterial culture supernatants or extracts are added to a growth medium containing the AHQ biosensor. Light output is proportional to the AHQ content of the sample. The assays described take approximately 2 days to complete, are simple to perform, do not require sophisticated instrumentation and are highly amenable to screening large numbers of bacterial samples. However, apart from PQS and HHQ in P. aeruginosa, definitive AHQ identification will require additional MS and NMR analyses.

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“…Examples of bacterial PAMPs include LPS, peptidoglycan, unmethylated CpG motifs present in DNA, and viral nucleic acids (13). Here we have examined a class of secreted molecules, the N-acylhomoserine lactones (AHLs), that are produced by a large number of Gram-negative bacteria (14). AHLs are a structurally highly conserved group of bacteria-derived molecules.…”

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confidence: 99%

N-(3-Oxo-acyl)homoserine Lactones Signal Cell Activation through a Mechanism distinct from the Canonical Pathogen-associated Molecular Pattern Recognition Receptor Pathways

Kravchenko

Kaufmann

Mathison

et al. 2006

Journal of Biological Chemistry

121

164

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Innate immune system receptors function as sensors of infection and trigger the immune responses through ligand-specific signaling pathways. These ligands are pathogen-associated products, such as components of bacterial walls and viral nuclear acids. A common response to such ligands is the activation of mitogen-activated protein kinase p38, whereas doublestranded viral RNA additionally induces the phosphorylation of eukaryotic translation initiation factor 2␣ (eIF2␣). Here we have shown that p38 and eIF2␣ phosphorylation represent two biochemical markers of the effects induced by N-(3-oxo-acyl)homoserine lactones, the secreted products of a number of Gramnegative bacteria, including the human opportunistic pathogen Pseudomonas aeruginosa. Furthermore, N-(3-oxo-dodecanoyl)homoserine lactone induced distension of mitochondria and the endoplasmic reticulum as well as c-jun gene transcription. These effects occurred in a wide variety of cell types including alveolar macrophages and bronchial epithelial cells, requiring the structural integrity of the lactone ring motif and its natural stereochemistry. These findings suggest that N-(3-oxo-acyl)homoserine lactones might be recognized by receptors of the innate immune system. However, we provide evidence that N-(3-oxo-dodecanoyl)homoserine lactone-mediated signaling does not require the presence of the canonical innate immune system receptors, Toll-like receptors, or two members of the NLR/Nod/Caterpillar family, Nod1 and Nod2. These data offer a new understanding of the effects of N-(3-oxo-dodecanoyl)homoserine lactone on host cells and its role in persistent airway infections caused by P. aeruginosa.

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Regulatory circuits and communication in Gram-negative bacteria

Cited by 203 publications

References 120 publications

Regulation of the biosynthesis of thiopeptide antibiotic cyclothiazomycin by the transcriptional regulator SHJG8833 in Streptomyces hygroscopicus 5008

Regulation of the biosynthesis of thiopeptide antibiotic cyclothiazomycin by the transcriptional regulator SHJG8833 in Streptomyces hygroscopicus 5008

Biosensor-based assays for PQS, HHQ and related 2-alkyl-4-quinolone quorum sensing signal molecules

N-(3-Oxo-acyl)homoserine Lactones Signal Cell Activation through a Mechanism distinct from the Canonical Pathogen-associated Molecular Pattern Recognition Receptor Pathways

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