The RNA Chaperone Hfq Regulates Antibiotic Biosynthesis in the Rhizobacterium Pseudomonas aeruginosa M18

Wang, Guohao; Huang, Xianqing; Li, Sainan; Huang, Jiaofang; Xue, Wei; Li, Yaqian; Xu, Yuquan

doi:10.1128/jb.00029-12

Cited by 23 publications

(35 citation statements)

References 55 publications

(91 reference statements)

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“…In P. aeruginosa M18, Hfq binds qscR and phzM mRNA transcripts via AU-rich sequences present in their 5 0 -leader sequences and inhibits their translation (Wang et al 2012b). As qscR is a negative regulator of the phz operons, and phzM is required for the conversion of PCA to PYO, Hfq would be expected to enhance phenazine production overall but limit PYO production.…”

Section: Post-transcriptional Regulationmentioning

confidence: 99%

Regulation of Phenazine Biosynthesis

Sakhtah

Price-Whelan

Dietrich

2013

Microbial Phenazines

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Microbiologists have historically been struck by both the beautiful pigmentation of phenazine-producing cultures and the high degree of variability in phenazine production among isolates, conditions, and even repeat experiments. Motivated by an interest in controlling phenazine biosynthesis, they have identified many of the factors that affect the regulation of this process. Phenazine production is controlled by complex regulatory networks. The variability of phenazine production can be explained in part by the effects of environmental conditions on these networks and by strain-specific differences in these networks. In this chapter, we describe the components of a common regulatory cascade that is represented in many phenazine-producing pseudomonads. Membrane sensor proteins and two component sensors control the activity of downstream regulators such as quorum sensing systems and RNA-binding proteins and small RNAs; these cytoplasmic regulators then control the production of phenazine biosynthetic proteins. We highlight examples from specific strains and cases where the mechanistic links may vary among them. We also discuss environmental parameters that have been shown to affect phenazine biosynthesis and compare their effects in different isolates. Ongoing work will further elaborate the details of the environmental sensing and regulatory responses that control production of these dramatically colored compounds. New findings have the potential to support enhanced application of phenazine-producing strains in agriculture, where they promote crop health, and the treatment of infections in which phenazines contribute to bacterial pathogenicity.

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Section: Post-transcriptional Regulationmentioning

confidence: 99%

Regulation of Phenazine Biosynthesis

Sakhtah

Price-Whelan

Dietrich

2013

Microbial Phenazines

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“…Multiple distinct regulatory characteristics of secondary metabolism, including the antibiotic biosynthesis shown by P. aeruginosa strain M18 isolated from the rhizosphere (4,(10)(11)(12)(13)(14)(15)(16)22), urged us to ascertain the genome-scale profiling of bacterial physiology and metabolism in the gacA mutant of the M18 strain. A general model of GacA-mediated global regulation in P. aeruginosa M18 is outlined in Fig.…”

Section: Discussionmentioning

confidence: 99%

“…The transcript level of qscR, a global QS regulator gene upstream of the phz2 operon, displayed a 3.3-fold decrease because of the gacA mutation. The qscR gene was also reported to mainly downregulate the expression of the phz2 operon (16).…”

Section: Gaca Acts As a Central Regulator Of Secondary Metabolismmentioning

confidence: 99%

“…A temperature of 37°C instead of 28°C is more favorable for phzM expression and PYO biosynthesis (14). Apart from the different and strong transcriptional regulation from all three P. aeruginosa quorum-sensing (QS) systems (Las, Rhl, and PQS) (11,12,15), antibiotic biosynthesis in the M18 strain is also subject to posttranscriptional regulation from the sRNA chaperone Hfq (16) and the Gac/Rsm signal transduction cascade (10,17).…”

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confidence: 99%

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Global Control of GacA in Secondary Metabolism, Primary Metabolism, Secretion Systems, and Motility in the Rhizobacterium Pseudomonas aeruginosa M18

et al. 2013

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The rhizobacterium Pseudomonas aeruginosa M18 can produce a broad spectrum of secondary metabolites, including the antibiotics pyoluteorin (Plt) and phenazine-1-carboxylic acid (PCA), hydrogen cyanide, and the siderophores pyoverdine and pyochelin. The antibiotic biosynthesis of M18 is coordinately controlled by multiple distinct regulatory pathways, of which the GacS/GacA system activates Plt biosynthesis but strongly downregulates PCA biosynthesis. Here, we investigated the global influence of a gacA mutation on the M18 transcriptome and related metabolic and physiological processes. Transcriptome profiling revealed that the transcript levels of 839 genes, which account for approximately 15% of the annotated genes in the M18 genome, were significantly influenced by the gacA mutation during the early stationary growth phase of M18. Most secondary metabolic gene clusters, such as pvd, pch, plt, amb, and hcn, were activated by GacA. The GacA regulon also included genes encoding extracellular enzymes and cytochrome oxidases. Interestingly, the primary metabolism involved in the assimilation and metabolism of phosphorus, sulfur, and nitrogen sources was also notably regulated by GacA. Another important category of the GacA regulon was secretion systems, including H1, H2, and H3 (type VI secretion systems [T6SSs]), Hxc (T2SS), and Has and Apr (T1SSs), and CupE and Tad pili. More remarkably, GacA inhibited swimming, swarming, and twitching motilities. Taken together, the Gac-initiated global regulation, which was mostly mediated through multiple regulatory systems or factors, was mainly involved in secondary and primary metabolism, secretion systems, motility, etc., contributing to ecological or nutritional competence, ion homeostasis, and biocontrol in M18. P seudomonas aeruginosa M18 is a unique and well-characterized biocontrol rhizobacterium showing a strong antifungal capability (1, 2). It can produce a diverse range of secondary metabolites, including antibiotics, siderophores, and extracellular enzymes, such as phenazine-1-carboxylic acid (PCA), pyoluteorin (Plt), hydrogen cyanide (HCN), L-2-amino-4-methoxy-trans-3-butenoic acid (AMB), pyoverdine, pyochelin, and alkaline protease (1, 2). In contrast to primary metabolism, which is essential for maintaining normal physiological processes, secondary metabolism is not absolutely required for bacterial survival but contributes to ecological and nutritional competence. AMB, a potent antibiotic and toxin, has received little attention (3). The antibiotics PCA and Plt mainly contribute to the strong antifungal capacity of the M18 strain. In the M18 genome, two copies of phenazine biosynthetic operons are highly homologous to each other and to those in P. aeruginosa PAO1 (2, 4). However, the Plt biosynthetic structural, regulatory, and transport gene cluster is conserved in gene organization and size between P. aeruginosa M18 and P. protegens Pf-5 (previously called P. fluorescens) but displays a certain level of difference in the nucleotide sequence, especially the n...

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“…Hfq is an RNA chaperone protein that acts as a global post-transcriptional regulatory protein by interacting with target mRNAs or facilitating the complementary base pairing between small non-coding RNAs and mRNAs [46]. Hfq was shown previously to positively regulate the production of bacterial secondary metabolites, including the antibiotic 2,4-diacetylphloroglucinol and phenazines in Pseudomonas species [47][48][49][50]. In E. coli K-12, the hfq gene contains three functional promoters, two of which are located inside the open reading frame of miaA [29,30,35].…”

Section: Miaa Affects Growth Of P Chlororaphis 30-84mentioning

confidence: 99%

Disruption of MiaA provides insights into the regulation of phenazine biosynthesis under suboptimal growth conditions in Pseudomonas chlororaphis 30-84

Wang

Pierson

et al. 2017

Microbiology

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Many products of secondary metabolism are activated by quorum sensing (QS), yet even at cell densities sufficient for QS, their production may be repressed under suboptimal growth conditions via mechanisms that still require elucidation. For many beneficial plant-associated bacteria, secondary metabolites such as phenazines are important for their competitive survival and plant-protective activities. Previous work established that phenazine biosynthesis in Pseudomonas chlororaphis 30-84 is regulated by the PhzR/PhzI QS system, which in turn is regulated by transcriptional regulator Pip, two-component system RpeA/RpeB and stationary phase/stress sigma factor RpoS. Disruption of MiaA, a tRNA modification enzyme, altered primary metabolism and growth leading to widespread effects on secondary metabolism, including reduced phenazine production and oxidative stress tolerance. Thus, the miaA mutant provided the opportunity to examine the regulation of phenazine production in response to altered metabolism and growth or stress tolerance. Despite the importance of MiaA for translation efficiency, the most significant effect of miaA disruption on phenazine production was the reduction in the transcription of phzR, phzI and pip, whereas neither the transcription nor translation of RpeB, a transcriptional regulator of pip, was affected. Constitutive expression of rpeB or pip in the miaA mutant completely restored phenazine production, but it resulted in further growth impairment. Constitutive expression of RpoS alleviated sensitivity to oxidative stress resulting from RpoS translation inefficiency in the miaA mutant, but it did not restore phenazine production. Our results support the model that cells curtail phenazine biosynthesis under suboptimal growth conditions via RpeB/Pip-mediated regulation of QS.

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The RNA Chaperone Hfq Regulates Antibiotic Biosynthesis in the Rhizobacterium Pseudomonas aeruginosa M18

Cited by 23 publications

References 55 publications

Regulation of Phenazine Biosynthesis

Regulation of Phenazine Biosynthesis

Global Control of GacA in Secondary Metabolism, Primary Metabolism, Secretion Systems, and Motility in the Rhizobacterium Pseudomonas aeruginosa M18

Disruption of MiaA provides insights into the regulation of phenazine biosynthesis under suboptimal growth conditions in Pseudomonas chlororaphis 30-84

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