Two sRNA RyhB homologs from Yersinia pestis biovar microtus expressed in vivo have differential Hfq-dependent stability

Deng, Zhongliang; Meng, Xiangli; Su, Shanchun; Liu, Zizhong; Ji, Xiaolan; Zhang, Yiquan; Zhao, Xiangna; Wang, Xiaoyi; Yang, Ruifu; Han, Yanping

doi:10.1016/j.resmic.2012.05.006

Cited by 49 publications

(60 citation statements)

References 28 publications

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“…Iron-responsive regulators in bacteria have largely been shown to contribute to iron homeostasis by one of two mechanisms: repressing the expression of iron uptake systems under iron-replete conditions and reducing the production of iron-containing proteins in iron-limiting environments. The latter of these functions is mediated in many bacterial species by iron-responsive sRNAs (32,34,(58)(59)(60)(61)(62)(63)(64)(65), and in some pathogenic species, these iron-regulated sRNAs affect the expression of virulence traits (33,63,64,66,67). Here, we show that deletion of the locus encoding the iron-responsive PrrF sRNAs of P. aeruginosa causes defects of iron and heme homeostasis, alters biofilm formation, affects virulence gene expression, and, most strikingly, attenuates virulence.…”

Section: Discussionmentioning

confidence: 78%

The prrF -Encoded Small Regulatory RNAs Are Required for Iron Homeostasis and Virulence of Pseudomonas aeruginosa

et al. 2015

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Pseudomonas aeruginosa is an opportunistic pathogen that requires iron to cause infection, but it also must regulate the uptake of iron to avoid iron toxicity. The iron-responsive PrrF1 and PrrF2 small regulatory RNAs (sRNAs) are part of P. aeruginosa's iron regulatory network and affect the expression of at least 50 genes encoding iron-containing proteins. The genes encoding the PrrF1 and PrrF2 sRNAs are encoded in tandem in P. aeruginosa, allowing for the expression of a distinct, heme-responsive sRNA named PrrH that appears to regulate genes involved in heme metabolism. Using a combination of growth, mass spectrometry, and gene expression analysis, we showed that the ⌬prrF1,2 mutant, which lacks expression of the PrrF and PrrH sRNAs, is defective for both iron and heme homeostasis. We also identified phuS, encoding a heme binding protein involved in heme acquisition, and vreR, encoding a previously identified regulator of P. aeruginosa virulence genes, as novel targets of prrF-mediated heme regulation. Finally, we showed that the prrF locus encoding the PrrF and PrrH sRNAs is required for P. aeruginosa virulence in a murine model of acute lung infection. Moreover, we showed that inoculation with a ⌬prrF1,2 deletion mutant protects against future challenge with wild-type P. aeruginosa. Combined, these data demonstrate that the prrF-encoded sRNAs are critical regulators of P. aeruginosa virulence. Pseudomonas aeruginosa is a ubiquitous Gram-negative bacterium and versatile opportunistic pathogen. Iron is required for P. aeruginosa virulence (1-6) and is obtained through several mechanisms. In anaerobic environments, iron in its ferrous form is freely diffusible through the outer membrane (OM) and transported into the cytoplasm by the Feo inner membrane transport system (7,8). However, the insolubility of ferric iron in aerobic environments limits accessibility to this nutrient. Moreover, the sequestration of iron by host proteins creates a substantial barrier to infection (9, 10). To overcome this barrier, P. aeruginosa synthesizes and secretes two siderophores, pyoverdine and pyochelin, which scavenge ferric iron (1-4). P. aeruginosa can also acquire heme, an abundant source of iron in the human host (11). Once internalized, heme is sequestered by the cytosolic PhuS heme chaperone (12). PhuS transfers heme to the iron-regulated HemO heme oxygenase, which degrades heme to biliverdin, releasing carbon monoxide and iron (13,14). Several studies have shown that iron acquisition is essential for P. aeruginosa virulence (1-5) and biofilm formation (15-17), demonstrating the central role of this element in P. aeruginosa pathogenesis.Despite its essentiality, iron and heme can be toxic due to their ability to catalyze the formation of reactive oxygen species. Thus, to maintain iron homeostasis, P. aeruginosa must be able to not only acquire iron but also regulate uptake of iron and heme from the environment, as well as iron use and storage. Expression of genes encoding iron and heme uptake systems in P. aeruginosa is ...

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Section: Discussionmentioning

confidence: 78%

The prrF -Encoded Small Regulatory RNAs Are Required for Iron Homeostasis and Virulence of Pseudomonas aeruginosa

et al. 2015

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“…In Shigella dysenteriae, the iron-responsive sRNA RyhB has been implicated in the repression of the transcriptional activator VirB, which leads to reduced transcription of T3SS genes (65). Interestingly, Y. pestis encodes 2 RyhB sRNAs (RyhB1 and RyhB2), which could also influence the regulation of the T3SS (31,66). It is of great interest to determine how Ysr141 links the posttranscriptional activation of the T3SS to environmental signals in Yersinia and whether these mechanisms are similar to those found in other species that regulate their T3SSs via Hfq and sRNAs.…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Analysis of Small RNAs Expressed by Yersinia pestis Identifies a Regulator of the Yop-Ysc Type III Secretion System

et al. 2014

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bSmall noncoding RNA (sRNA) molecules are integral components of the regulatory machinery for many bacterial species and are known to posttranscriptionally regulate metabolic and stress-response pathways, quorum sensing, virulence factors, and more. The Yop-Ysc type III secretion system (T3SS) is a critical virulence component for the pathogenic Yersinia species, and the regulation of this system is tightly controlled at each step from transcription to translocation of effectors into host cells. The contribution of sRNAs to the regulation of the T3SS in Yersinia has been largely unstudied, however. Previously, our lab identified a role for the sRNA chaperone protein Hfq in the regulation of components of the T3SS in the gastrointestinal pathogen Yersinia pseudotuberculosis. Here we present data demonstrating a similar requirement for Hfq in the closely related species Yersinia pestis. Through deep sequencing analysis of the Y. pestis sRNA-ome, we found 63 previously unidentified putative sRNAs in this species. We identified a Yersinia-specific sRNA, Ysr141, carried by the T3SS plasmid pCD1 that is required for the production of multiple T3SS proteins. In addition, we show that Ysr141 targets an untranslated region upstream of yopJ to posttranscriptionally activate the synthesis of the YopJ protein. Furthermore, Ysr141 may be an unstable and/or processed sRNA, which could contribute to its function in the regulation of the T3SS. The discovery of an sRNA that influences the synthesis of the T3SS adds an additional layer of regulation to this tightly controlled virulence determinant of Y. pestis.

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“…The sibling RNAs RyhB1/RyhB2 are both activated after iron scarcity by inactivation of the ferric uptake regulator Fur (79). Both ncRNAs are functionally redundant, but RyhB1 seems slightly more sensitive to alterations of degradosome factors (79,80).…”

Section: Growth In Lymphatic Tissues Alters the Abundance Of Conservedmentioning

confidence: 99%

“…Both ncRNAs are functionally redundant, but RyhB1 seems slightly more sensitive to alterations of degradosome factors (79,80). They both regulate iron homeostasis by up-regulation of iron-scavenging systems and repression of nonessential ironcontaining proteins to liberate iron (79,81).…”

Section: Growth In Lymphatic Tissues Alters the Abundance Of Conservedmentioning

confidence: 99%

Tissue dual RNA-seq allows fast discovery of infection-specific functions and riboregulators shaping host–pathogen transcriptomes

Nuss

Beckstette

Пименова

et al. 2017

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

137

117

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Pathogenic bacteria need to rapidly adjust their virulence and fitness program to prevent eradication by the host. So far, underlying adaptation processes that drive pathogenesis have mostly been studied in vitro, neglecting the true complexity of host-induced stimuli acting on the invading pathogen. In this study, we developed an unbiased experimental approach that allows simultaneous monitoring of genome-wide infection-linked transcriptional alterations of the host and colonizing extracellular pathogens. Using this tool for Yersinia pseudotuberculosis-infected lymphatic tissues, we revealed numerous alterations of host transcripts associated with inflammatory and acute-phase responses, coagulative activities, and transition metal ion sequestration, highlighting that the immune response is dominated by infiltrating neutrophils and elicits a mixed T H 17/T H 1 response. In consequence, the pathogen's response is mainly directed to prevent phagocytic attacks. Yersinia up-regulates the gene and expression dose of the antiphagocytic type III secretion system (T3SS) and induces functions counteracting neutrophil-induced ion deprivation, radical stress, and nutritional restraints. Several conserved bacterial riboregulators were identified that impacted this response. The strongest influence on virulence was found for the loss of the carbon storage regulator (Csr) system, which is shown to be essential for the up-regulation of the T3SS on host cell contact. In summary, our established approach provides a powerful tool for the discovery of infection-specific stimuli, induced host and pathogen responses, and underlying regulatory processes.tissue dual RNA-seq | host-pathogen interaction | host-adapted metabolism | noncoding RNAs | Yersinia

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Two sRNA RyhB homologs from Yersinia pestis biovar microtus expressed in vivo have differential Hfq-dependent stability

Cited by 49 publications

References 28 publications

The prrF -Encoded Small Regulatory RNAs Are Required for Iron Homeostasis and Virulence of Pseudomonas aeruginosa

The prrF -Encoded Small Regulatory RNAs Are Required for Iron Homeostasis and Virulence of Pseudomonas aeruginosa

Genome-Wide Analysis of Small RNAs Expressed by Yersinia pestis Identifies a Regulator of the Yop-Ysc Type III Secretion System

Tissue dual RNA-seq allows fast discovery of infection-specific functions and riboregulators shaping host–pathogen transcriptomes

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