Three small RNAs jointly ensure secondary metabolism and biocontrol in
            <i>Pseudomonas fluorescens</i>
            CHA0

Kay, Elisabeth; Dubuis, Christophe; Haas, Dieter

doi:10.1073/pnas.0505673102

Cited by 205 publications

(263 citation statements)

References 43 publications

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“…Translation of mRNAs can continue when the cell expresses high quantities of small RNAs that compete for binding to RsmA, which is similar to the carbon storage regulator, CsrA from E. coli and the regulation of sRNA expression is promoted by a two-component system named GacS/GacA. 42 …”

Section: Carbon Source Regulation Of Antibiotic Production In Gram-nementioning

confidence: 99%

Carbon source regulation of antibiotic production

et al. 2010

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Section: Carbon Source Regulation Of Antibiotic Production In Gram-nementioning

confidence: 99%

Carbon source regulation of antibiotic production

et al. 2010

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“…1A), and the sRNA antagonists are structurally and functionally similar (29). Species-specific differences in regulation appear to be a result of two-component systems that control expression of the sRNAs and RNases that control their stability (26,27,(30)(31)(32)(33)(34). Little is known about the precise environmental signals that control sRNA expression, and therefore CsrA function (35).…”

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confidence: 99%

“…CsrA-deficient bacterial pathogens are typically attenuated for virulence, which is likely a result of misregulation of target gene expression and the resulting inability to make critical physiological transitions during an infection (1,(21)(22)(23). To further regulate these transitions, small RNAs (sRNAs) containing as many as 20 CsrA binding sites competitively inhibit CsrA by sequestering it from its native mRNA targets (24)(25)(26)(27)(28). The primary sequence of CsrA is highly conserved in the γ-proteobacteria (Fig.…”

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confidence: 99%

FliW antagonizes CsrA RNA binding by a noncompetitive allosteric mechanism

Mukherjee

Oshiro

Yakhnin

et al. 2016

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

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CsrA (carbon storage regulator A) is a widely distributed bacterial RNA binding protein that regulates translation initiation and mRNA stability of target transcripts. In γ-proteobacteria, CsrA activity is competitively antagonized by one or more small RNAs (sRNAs) containing multiple CsrA binding sites, but CsrA in bacteria outside the γ-proteobacteria is antagonized by a protein called FliW. Here we show that FliW of Bacillus subtilis does not bind to the same residues of CsrA required for RNA binding. Instead, CsrA mutants resistant to FliW antagonism (crw) altered residues of CsrA on an allosteric surface of previously unattributed function. Some crw mutants abolished CsrA–FliW binding, but others did not, suggesting that FliW and RNA interaction is not mutually exclusive. We conclude that FliW inhibits CsrA by a noncompetitive mechanism that differs dramatically from the well-established sRNA inhibitors. FliW is highly conserved with CsrA in bacteria, appears to be the ancestral form of CsrA regulation, and represents a widespread noncompetitive mechanism of CsrA control.

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“…In the opportunistic human pathogen Pseudomonas aeruginosa, there are only two functionally equivalent, GacA-controlled sRNAs, RsmY and RsmZ. These sRNAs have a high affinity for the RNA-binding protein RsmA and additionally for the RsmA paralogue RsmE in strain CHA0 (11,12,16,17). The RsmA and RsmE proteins repress the translation of genes involved in secondary metabolism during the trophophase.…”

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confidence: 99%

“…The Gac/Rsm cascade is initiated by the GacS/ GacA two-component system (8,10). At high cell population densities, Pseudomonas species excrete chemically uncharacterized signal molecules that can act as inducers of the Gac/Rsm pathway by favoring phosphorylation of the GacS sensor kinase and hence of the cognate GacA response regulator (11)(12)(13)(14). Activated GacA promotes the transcription of two or three non-coding small RNAs (sRNAs), 4 depending on the species.…”

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confidence: 99%

Small RNA-dependent Expression of Secondary Metabolism Is Controlled by Krebs Cycle Function in Pseudomonas fluorescens

Takeuchi

Kiefer

Reimmann

et al. 2009

Journal of Biological Chemistry

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Pseudomonas fluorescens CHA0, an antagonist of phytopathogenic fungi in the rhizosphere of crop plants, elaborates and excretes several secondary metabolites with antibiotic properties. Their synthesis depends on three small RNAs (RsmX, RsmY, and RsmZ), whose expression is positively controlled by the GacS-GacA two-component system at high cell population densities. To find regulatory links between primary and secondary metabolism in P. fluorescens and in the related species Pseudomonas aeruginosa, we searched for null mutations that affected central carbon metabolism as well as the expression of rsmY-gfp and rsmZ-gfp reporter constructs but without slowing down the growth rate in rich media. Mutation in the pycAB genes (for pyruvate carboxylase) led to down-regulation of rsmXYZ and secondary metabolism, whereas mutation in fumA (for a fumarase isoenzyme) resulted in up-regulation of the three small RNAs and secondary metabolism in the absence of detectable nutrient limitation. These effects required the GacS sensor kinase but not the accessory sensors RetS and LadS. An analysis of intracellular metabolites in P. fluorescens revealed a strong positive correlation between small RNA expression and the pools of 2-oxoglutarate, succinate, and fumarate. We conclude that Krebs cycle intermediates (already known to control GacA-dependent virulence factors in P. aeruginosa) exert a critical trigger function in secondary metabolism via the expression of GacA-dependent small RNAs.Secondary metabolism occurs in certain bacteria and fungi as part of developmental processes, which are often accompanied by morphological changes (1, 2). In natural environments, secondary metabolites are believed to confer a selective advantage to the producers when these organisms cannot rely on their full growth potential to compete with other organisms (3). Such a role is most plausible for secondary metabolites having antibiotic activities (4). In pure cultures, secondary metabolites are non-essential for the producers and are typically formed when cell population densities are high and growth is restricted. This distinct production phase, sometimes called idiophase, usually follows the phase of optimal growth, also termed trophophase (5). A fundamental question is what triggers the onset of the idiophase. Both extracellular and intracellular signal molecules are known to be involved. For instance, excreted quorum-sensing signal molecules, such as N-acyl-homoserine lactones of Pseudomonas species or ␥-butyrolactones of Streptomyces species, positively regulate the expression of antibiotic compounds, and the intracellular alarmone ppGpp is required for antibiotic production in Streptomyces coelicolor under conditions of nitrogen starvation (1, 6). However, these findings do not provide a generally valid picture of how secondary metabolism is initiated in microorganisms. For instance, some Pseudomonas species produce secondary metabolites without N-acyl-homoserine lactones and phosphate-limited S. coelicolor does not rely on ppGpp for antibio...

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Three small RNAs jointly ensure secondary metabolism and biocontrol in Pseudomonas fluorescens CHA0

Cited by 205 publications

References 43 publications

Carbon source regulation of antibiotic production

Carbon source regulation of antibiotic production

FliW antagonizes CsrA RNA binding by a noncompetitive allosteric mechanism

Small RNA-dependent Expression of Secondary Metabolism Is Controlled by Krebs Cycle Function in Pseudomonas fluorescens

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