Structural Rearrangement in an RsmA/CsrA Ortholog of Pseudomonas aeruginosa Creates a Dimeric RNA-Binding Protein, RsmN

Morris, Elizabeth R.; Hall, G. G.; Li, Chan; Heeb, Stephan; Kulkarni, Rahul; Lovelock, Laura; Silistre, Hazel; Messina, Marco; Cámara, Miguel; Emsley, Jonas; Williams, Paul; Searle, Mark S.

doi:10.1016/j.str.2013.07.007

Cited by 81 publications

(108 citation statements)

References 43 publications

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“…6). For example, RsmF is a homodimer that contains antiparallel ␤-sheets formed by ␤1, ␤3, and ␤4 from one polypeptide and ␤2 and ␤5 from the opposite polypeptide (157,175). This is in contrast to the case for CsrA/RsmA/RsmE, wherein ␤-sheets are formed by ␤2, ␤3, and ␤4 from one polypeptide and ␤1 and ␤5 from the opposite polypeptide.…”

Section: P Aeruginosamentioning

confidence: 98%

“…In contrast, RsmA and RsmF (RsmN) in P. aeruginosa share only 31% amino acid identity and have both shared and exclusive RNA targets (157,175). The rsmF deletion strain appears phenotypically virtually indistinguishable from wild-type cells when comparing the expression of known RsmA targets, including genes involved in biofilm, T3SS, and T6SS.…”

Section: P Aeruginosamentioning

confidence: 99%

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Regulation of Bacterial Virulence by Csr (Rsm) Systems

Vakulskas

Potts

Babitzke

et al. 2015

Microbiol Mol Biol Rev

302

400

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SUMMARY Most bacterial pathogens have the remarkable ability to flourish in the external environment and in specialized host niches. This ability requires their metabolism, physiology, and virulence factors to be responsive to changes in their surroundings. It is no surprise that the underlying genetic circuitry that supports this adaptability is multilayered and exceedingly complex. Studies over the past 2 decades have established that the CsrA/RsmA proteins, global regulators of posttranscriptional gene expression, play important roles in the expression of virulence factors of numerous proteobacterial pathogens. To accomplish these tasks, CsrA binds to the 5′ untranslated and/or early coding regions of mRNAs and alters translation, mRNA turnover, and/or transcript elongation. CsrA activity is regulated by noncoding small RNAs (sRNAs) that contain multiple CsrA binding sites, which permit them to sequester multiple CsrA homodimers away from mRNA targets. Environmental cues sensed by two-component signal transduction systems and other regulatory factors govern the expression of the CsrA-binding sRNAs and, ultimately, the effects of CsrA on secretion systems, surface molecules and biofilm formation, quorum sensing, motility, pigmentation, siderophore production, and phagocytic avoidance. This review presents the workings of the Csr system, the paradigm shift that it generated for understanding posttranscriptional regulation, and its roles in virulence networks of animal and plant pathogens.

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Section: P Aeruginosamentioning

confidence: 98%

Section: P Aeruginosamentioning

confidence: 99%

Regulation of Bacterial Virulence by Csr (Rsm) Systems

Vakulskas

Potts

Babitzke

et al. 2015

Microbiol Mol Biol Rev

302

400

View full text Add to dashboard Cite

show abstract

“…In the end, experimental evolution studies are limited by the fact that what happens in the laboratory may not reflect precisely what happens in natural systems. However, there is natural variation in Rsm homolog copy number in the pseudomonads (25,28,42), so the gain and loss of Rsm proteins is part of the evolutionary trajectory of natural systems.…”

Section: L I L T R K V G E S I N I G D D I T I T I L G V S G Q Q V mentioning

confidence: 99%

Importance of positioning for microbial evolution

Kim

Racimo

Schluter

et al. 2014

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

144

207

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Microbes commonly live in dense surface-attached communities where cells layer on top of one another such that only those at the edges have unimpeded access to limiting nutrients and space. Theory predicts that this simple spatial effect, akin to plants competing for light in a forest, generates strong natural selection on microbial phenotypes. However, we require direct empirical tests of the importance of this spatial structuring. Here we show that spontaneous mutants repeatedly arise, push their way to the surface, and dominate colonies of the bacterium Pseudomonas fluorescens Pf0-1. Microscopy and modeling suggests that these mutants use secretions to expand and push themselves up to the growth surface to gain the best access to oxygen. Physically mixing the cells in the colony, or introducing space limitations, largely removes the mutant's advantage, showing a key link between fitness and the ability of the cells to position themselves in the colony. We next follow over 500 independent adaptation events and show that all occur through mutation of a single repressor of secretions, RsmE, but that the mutants differ in competitiveness. This process allows us to map the genetic basis of their adaptation at high molecular resolution and we show how evolutionary competitiveness is explained by the specific effects of each mutation. By combining population level and molecular analyses, we demonstrate how living in dense microbial communities can generate strong natural selection to reach the growing edge.bacteria | biofilm | experimental evolution | social interaction

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“…Furthermore, many other systems can affect the activity of the Gac system, thus modulating the levels of these RsmA-repressing sRNAs (Goodman et al, 2004(Goodman et al, , 2009Ventre et al, 2006). The importance of post-transcriptional regulation in P. aeruginosa is more complex than initially thought, as a new post-transcriptional regulator (RsmN), which shares little structural homology with RsmA, but possesses a similar mechanism of action, was reported recently (Marden et al, 2013;Morris et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Complex autoregulation of the post-transcriptional regulator RsmA in Pseudomonas aeruginosa

2015

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RsmA is a post-transcriptional RNA-binding protein that acts as a pleiotropic global regulator of mRNAs in the opportunistic pathogen Pseudomonas aeruginosa. Upon binding to its target, RsmA impedes the translation of the mRNA by the ribosome. The RsmA regulon affects over 500 genes, many of which have been identified as important in the pathogenicity of P. aeruginosa. Whilst the regulatory function of RsmA is relatively well characterized, the genetic regulation of rsmA itself at the transcriptional and translational levels remains poorly understood. Here, we show that RsmA is capable of self-regulation through an unorthodox mechanism. This regulation occurs via direct interaction of the protein with an RsmA-binding site located in the early portion of its coding sequence. To the best of our knowledge this is the first report of such an unusual regulation in pseudomonads.

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Structural Rearrangement in an RsmA/CsrA Ortholog of Pseudomonas aeruginosa Creates a Dimeric RNA-Binding Protein, RsmN

Cited by 81 publications

References 43 publications

Regulation of Bacterial Virulence by Csr (Rsm) Systems

Regulation of Bacterial Virulence by Csr (Rsm) Systems

Importance of positioning for microbial evolution

Complex autoregulation of the post-transcriptional regulator RsmA in Pseudomonas aeruginosa

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