Control of Virulence by Small RNAs in Streptococcus pneumoniae

Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America.
PLoS Pathogens (Impact Factor: 7.56). 07/2012; 8(7):e1002788. DOI: 10.1371/journal.ppat.1002788
Source: PubMed


Author Summary
Pneumonia is a leading cause of childhood mortality worldwide, resulting in more deaths in young children than any other infectious disease. One of the leading causes of pneumonia is the human pathogen, Streptococcus pneumoniae, the causative agent of over six million infections each year in the United States. Understanding how bacterial pathogens rapidly respond to dynamic host environments is a central aspect of microbial pathogenesis. Accumulating evidence has implicated sRNAs as vital regulators in a number of important cellular processes though few have been implicated in virulence. In our investigations we have applied next-generation sequencing to define the sRNA repertoire of S. pneumoniae. In addition, we utilized both targeted genetic knockouts and transposon mutagenesis to show that a significant portion of these sRNAs play important roles at various stages of pneumococcal pathogenesis. These data represent the first example of sRNAs being involved in pneumococcal pathogenesis and greatly expand the number of sRNAs that play important roles in bacterial pathogenesis.

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Available from: Yong-Dong Wang
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    • "Some ncRNAs have also proved to play an important role in bacteria adhesion. For example, Mann et al. (2012) observed that DF20 and DF32/transfer messenger RNA could decrease adhesion to the nasopharyngeal or endothelial cells, respectively, of Streptococcus pneumoniae. OmpA protein is essential for adhesion of Escherichia coli to HeLa epithelial cells and Caco-2 colonic epithelial cells, while VrrA RNA has proved to affect Vibrio cholerae virulence by regulating the expression of OmpA and TcpA (Torres and Kaper, 2003; Song et al., 2008). "
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    ABSTRACT: The capability of Vibrio alginolyticus to adhere to fish mucus is a key virulence factor of the bacteria. Our previous research showed that stress conditions, such as Cu(2+), Pb(2+), Hg(2+), and low pH, can reduce this adhesion ability. Non-coding (nc) RNAs play a crucial role in regulating bacterial gene expression, affecting the bacteria's pathogenicity. To investigate the mechanism(s) underlying the decline in adhesion ability caused by stressors, we combined high-throughput sequencing with computational techniques to detect stressed ncRNA dynamics. These approaches yielded three commonly altered ncRNAs that are predicted to regulate the bacterial chemotaxis pathway, which plays a key role in the adhesion process of bacteria. We hypothesized they play a key role in the adhesion process of V. alginolyticus. In this study, we validated the effects of these three ncRNAs on their predicted target genes and their role in the V. alginolyticus adhesion process with RNA interference (i), quantitative real-time polymerase chain reaction (qPCR), northern blot, capillary assay, and in vitro adhesion assays. The expression of these ncRNAs and their predicted target genes were confirmed by qPCR and northern blot, which reinforced the reliability of the sequencing data and the target prediction. Overexpression of these ncRNAs was capable of reducing the chemotactic and adhesion ability of V. alginolyticus, and the expression levels of their target genes were also significantly reduced. Our results indicated that these three ncRNAs: (1) are able to regulate the bacterial chemotaxis pathway, and (2) play a key role in the adhesion process of V. alginolyticus.
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    • "CiaRH two-component system has been implicated in β-lactam susceptibility, autolysis, bacteriocin production, competence, and virulence, and some of these functions appear to be mediated by the csRNAs. For instance, stationary-phase autolysis was affected by csRNA4 and csRNA5 (Halfmann et al., 2007), and csRNA5 was defective in lung infectivity (Mann et al., 2012). But one of the most apparent phenotypes associated with CiaRH is blocking of spontaneous competence upon CiaRH activation (Guenzi et al., 1994; Müller et al., 2011). "
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    ABSTRACT: Streptococcus pneumoniae is a prominent human pathogen responsible for many severe diseases and the leading cause of childhood mortality worldwide. The pneumococcus is remarkably adept at colonizing and infecting different niches in the human body, and its adaptation to dynamic host environment is a central aspect of its pathogenesis. In the last decade, increasing findings have evidenced small RNAs (sRNAs) as vital regulators in a number of important processes in bacteria. In S. pneumoniae, a small antisense RNA was first discovered in the pMV158 plasmid as a copy number regulator. More recently, genome-wide screens revealed that the pneumococcal genome also encodes multiple sRNAs, many of which have important roles in virulence while some are implicated in competence control. The knowledge of the sRNA-mediated regulation in pneumococcus remains very limited, and future research is needed for better understanding of functions and mechanisms. Here, we provide a comprehensive summary of the current knowledge on sRNAs from Streptococcus pneumoniae, focusing mainly on the trans-encoded sRNAs.
    Full-text · Article · Apr 2015 · Frontiers in Genetics
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    • "In general, research into the RNA-mediated regulation of Gram-positive bacterial species lags behind that of Gram-negative species. The importance of RNA-mediated regulatory mechanisms in the virulence of Gram-positive pathogens (Johansson et al., 2002; Mann et al., 2012; Brantl and Bruckner, 2014), as well as apparent "
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    ABSTRACT: RNA-based mechanisms of regulation represent a ubiquitous class of regulators that are associated with diverse processes including nutrient sensing, stress response, modulation of horizontal gene transfer, and virulence factor expression. While better studied in Gram-negative bacteria, the literature is replete with examples of the importance of RNA-mediated regulatory mechanisms to the virulence and fitness of Gram-positives. Regulatory RNAs are classified as cis-acting, e.g. riboswitches, which modulate the transcription, translation, or stability of co-transcribed RNA, or trans-acting, e.g. small regulatory RNAs, which target separate mRNAs or proteins. The group A Streptococcus (GAS, Streptococcus pyogenes) is a Gram-positive bacterial pathogen from which several regulatory RNA mechanisms have been characterized. The study of RNA-mediated regulation in GAS has uncovered novel concepts with respect to how small regulatory RNAs may positively regulate target mRNA stability, and to how CRISPR RNAs are processed from longer precursors. This review provides an overview of RNA-mediated regulation in Gram-positive bacteria, and is highlighted with specific examples from GAS research. The key roles that these systems play in regulating bacterial virulence are discussed and future perspectives outlined.
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