A Salmonella Small Non-Coding RNA Facilitates Bacterial Invasion and Intracellular Replication by Modulating the Expression of Virulence Factors

Gong, Hao; Vu, Gia-Phong; Bai, Yongping; Chan, Elton; Wu, Ruo-bin; Yang, Edward; Liu, Fenyong; Lu, Sangwei

doi:10.1371/journal.ppat.1002120

Cited by 105 publications

(96 citation statements)

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“…The resulting lncRNA products might simply represent byproducts of transcription and are typically rapidly degraded after synthesis (Clark et al, 2012). (Albrecht et al, 2010(Albrecht et al, , 2011Chabelskaya et al, 2014;Chao et al, 2012;Gong et al, 2011;Grieshaber et al, 2006;Mann et al, 2012;Moon et al, 2013;Ortega et al, 2012;PadalonBrauch et al, 2008;Pfeiffer et al, 2007) crRNA, (Bhaya et al, 2011;Heidrich and Vogel, 2013;Sampson et al, 2013;van der Oost et al, 2014) (Georg and Hess, 2011;Giangrossi et al, 2010;GonzaloAsensio et al, 2013;Gottesman and Storz, 2011;Lasa et al, 2011;Lee and Groisman, 2010;Padalon-Brauch et al, 2008;Sesto et al, 2013) circRNAs rare varies arise from the 3'-5' ligation of both ends of linear RNA molecules n. a. -- (Doose et al, 2013;Vicens and Cech, 2009) - (Conway et al, 2014;Weinberg et al, 2009) Carpenter et al, 2013;Gomez et al, 2013;Iiott et al, 2014;Imamura et al, 2014;Li et al, 2014;Rapicavoli et al, 2013) poly ( …”

Section: Eukaryotic Long Non-coding Rnas (Lncrnas)mentioning

confidence: 99%

“…For instance, the FUR-regulated sRNAs RyhB and IsrE have been found to be highly induced in a fibroblast model of Salmonella infection (Ortega et al, 2012). Many pathogenicity island-encoded sRNAs (Isr genes) are activated inside macrophages (Gong et al, 2011;Padalon-Brauch et al, 2008) and numerous additional sRNAs undergo strong expression changes during growth over a range of infection-mimicking in vitro conditions (Kroger et al, 2013). Moreover, in vitro studies with Salmonella and pathogenic E. coli suggest various sRNAs that contribute to pathogenicity.…”

Section: Non-coding Rnas Involved In Virulence Infection and Immunitymentioning

confidence: 99%

“…This means that the mere intracellular induction of a given sRNA cannot be considered strict evidence for it giving rise to a virulence phenotype when deleted. and to regulate the expression of hilE, encoding a negative regulator of SPI-1 (Gong et al, 2011).…”

Section: Molecular Phenotyping Of Deletion Mutants Of Entire Srna Regmentioning

confidence: 99%

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Dual RNA-seq of pathogen and host

2012

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SummaryThe infection of a eukaryotic host cell by a bacterial pathogen is one of the most intimate examples of cross-kingdom interactions in biology. Infection processes are highly relevant from both a basic research as well as a clinical point of view. Sophisticated mechanisms have evolved in the pathogen to manipulate the host response and vice versa host cells have developed a wide range of anti-microbial defense strategies to combat bacterial invasion and clear infections.However, it is this diversity and complexity that makes infection research so challenging to technically address as common approaches have either been optimized for bacterial or eukaryotic organisms. Instead, methods are required that are able to deal with the often dramatic discrepancy between host and pathogen with respect to various cellular properties and processes. One class of cellular macromolecules that exemplify this host-pathogen heterogeneity is given by their transcriptomes: Bacterial transcripts differ from their eukaryotic counterparts in many aspects that involve both quantitative and qualitative traits. The entity of RNA transcripts present in a cell is of paramount interest as it reflects the cell's physiological state under the given condition. Genome-wide transcriptomic techniques such as RNA-seq have therefore been used for single-organism analyses for several years, but their applicability has been limited for infection studies.The present work describes the establishment of a novel transcriptomic approach for infection biology which we have termed "Dual RNA-seq". Using this technology, it was intended to shed light particularly on the contribution of non-protein-encoding transcripts to virulence, as these classes have mostly evaded previous infection studies due to the lack of suitable methods. The performance of Dual RNA-seq was evaluated in an in vitro infection model based on the important facultative intracellular pathogen Salmonella enterica serovar Typhimurium and different human cell lines. Dual RNA-seq was found to be capable of capturing all major bacterial and human transcript classes and proved reproducible. During the course of these experiments, a previously largely uncharacterized bacterial small non-coding RNA (sRNA), referred to as STnc440, was identified as one of the most strongly induced genes in intracellular Salmonella.Interestingly, while inhibition of STnc440 expression has been previously shown to cause a virulence defect in different animal models of Salmonellosis, the underlying molecular mechanisms have remained obscure. Here, classical genetics, transcriptomics and biochemical assays proposed a complex model of Salmonella gene expression control that is orchestrated by this sRNA. In particular, STnc440 was found to be involved in the regulation of multiple bacterial target mRNAs by direct base pair interaction with consequences for Salmonella virulence and

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Section: Eukaryotic Long Non-coding Rnas (Lncrnas)mentioning

confidence: 99%

Section: Non-coding Rnas Involved In Virulence Infection and Immunitymentioning

confidence: 99%

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Dual RNA-seq of pathogen and host

2012

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“…The Mlc global regulator has been shown to downregulate an hilE promoter (27). The small noncoding RNA isrM targets the hilE transcript to reduce the repressing activity of hilE (57). The LysR-type regulator LeuO has been shown to activate hilE transcription to repress HilD activity (58).…”

Section: Discussionmentioning

confidence: 99%

Two-Component Regulators Control hilA Expression by Controlling fimZ and hilE Expression within Salmonella enterica Serovar Typhimurium

Baxter

Jones

2015

Infect Immun

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c Salmonellae initiate disease through the invasion of host cells within the intestine. This ability to invade requires the coordinated action of numerous genes, many of which are found within Salmonella pathogenicity island 1 (SPI-1). The key to this process is the ability of the bacteria to respond to the environment, thereby upregulating the necessary genes under optimal conditions. Central to the control of SPI-1 is the transcriptional activator hilA. Work has identified at least 10 different activators and 8 different repressors responsible for the control of hilA. We have previously shown that hilE is a Salmonella-specific negative regulator that is able to repress hilA expression and invasion. Additionally, fimZ, a transcriptional activator responsible for the expression of type I fimbriae as well as flagellar genes, has also been implicated in this process. fimZ is homologous to response regulators from other two-component regulatory systems, although a sensor for the system has not been identified. The phoPQ and phoBR regulons are both two-component systems that negatively affect hilA expression, although the mechanism of action has not been determined. Our results show that PhoBR is capable of inducing fimZ expression, whereas PhoPQ does not affect fimZ expression but does upregulate hilE in an FimZ-dependent manner. Therefore, phosphate (sensed by PhoBR) and magnesium (sensed by PhoPQ) levels are important in controlling hilA expression levels when Salmonella is in the intestinal environment. Salmonellae have caused disease for many years. These Gramnegative bacteria can be transmitted through meat, dairy products, or eggs, from animals through the fecal-oral route, and indirectly via fecally contaminated water (1). The CDC tracks two forms of the disease, salmonellosis and typhoid fever. Salmonellosis is a mild form of disease that is typically confined to the gastrointestinal tract. It produces symptoms of fever, abdominal cramps, nausea, and diarrhea (2). A common feature of gastroenteritis or typhoid fever is the ability of Salmonella to invade host cells.Salmonella contains an island known as pathogenicity island 1 (SPI-1). This island is responsible for encoding both the structural proteins necessary for creating a type III secretion needle complex as well as some of the secreted effectors responsible for the manipulation of host cells (3, 4). Central to the control of this island is the transcriptional activator hilA, which needs to be upregulated for invasion to occur. This upregulation leads to the increased expression of all the other genes contained within SPI-1 (5, 6). Many different activators and repressors of hilA have been identified. These activators respond to a myriad of environmental signals, specifically, osmolarity, oxygen, pH, growth state, shortchain fatty acids, bile, and temperature (6-12), leading to precise control of hilA expression. The transcriptional activators HilD and HilC play an important role in controlling hilA expression. Work has shown that both genes are encode...

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“…InvR sRNA acts as a repressor of OmpD protein synthesis (Pfeiffer et al, 2007). IsrM sRNA, which is encoded by a Salmonella pathogenicity island, targets the mRNAs coding for SopA, a SPI-1 effector, and HilE, a global regulator of the expression of SPI-1 proteins (Gong et al, 2011). SgrS sRNA post-transcriptionally represses the expression of the secreted virulence factor SopD .…”

Section: Introductionmentioning

confidence: 99%