A Repeat-Associated Small RNA Controls the Major Virulence Factors of Helicobacter pylori

Eisenbart, Sara K.; Alzheimer, Mona; Pernitzsch, Sandy R.; Dietrich, Sascha; Stahl, Stephanie; Sharma, Cynthia M.

doi:10.1016/j.molcel.2020.09.009

Cited by 28 publications

(37 citation statements)

References 105 publications

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“…Multiple binding sequences in the cagA CDS may facilitate efficient reduction of cagA transcript levels in response to HPnc4160. While the present manuscript was under revision, Eisenbart et al published a paper describing that the nickel-responsive transcriptional regulator NikR regulates the expression of HPnc4160 (which the authors of that study renamed as 'NikS'), and HPnc4160 represses multiple major virulence genes, including cagA and vacA in vitro 29 . They showed that HPnc4160 binds to the 5′UTR of the cagA mRNA of strain G27.…”

Section: Discussionmentioning

confidence: 93%

A bacterial small RNA regulates the adaptation of Helicobacter pylori to the host environment

et al. 2021

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Long-term infection of the stomach with Helicobacter pylori can cause gastric cancer. However, the mechanisms by which the bacteria adapt to the stomach environment are poorly understood. Here, we show that a small non-coding RNA of H. pylori (HPnc4160, also known as IsoB or NikS) regulates the pathogen’s adaptation to the host environment as well as bacterial oncoprotein production. In a rodent model of H. pylori infection, the genomes of bacteria isolated from the stomach possess an increased number of T-repeats upstream of the HPnc4160-coding region, and this leads to reduced HPnc4160 expression. We use RNA-seq and iTRAQ analyses to identify eight targets of HPnc4160, including genes encoding outer membrane proteins and oncoprotein CagA. Mutant strains with HPnc4160 deficiency display increased colonization ability of the mouse stomach, in comparison with the wild-type strain. Furthermore, HPnc4160 expression is lower in clinical isolates from gastric cancer patients than in isolates derived from non-cancer patients, while the expression of HPnc4160’s targets is higher in the isolates from gastric cancer patients. Therefore, the small RNA HPnc4160 regulates H. pylori adaptation to the host environment and, potentially, gastric carcinogenesis.

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Section: Discussionmentioning

confidence: 93%

A bacterial small RNA regulates the adaptation of Helicobacter pylori to the host environment

et al. 2021

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“…NikS/HPnc4160, A sRNA Regulating Major Virulence Factors in H. pylori Two recent publications report the characterization of a sRNA (HPnc4160) that regulates the expression of major H. pylori virulence factors (Eisenbart et al, 2020;Kinoshita-Daitoku et al, 2021). HPnc4160 was previously identified as a highly transcribed sRNA (IsoB) expressed from the opposite strand of a poorly expressed small ORF (AapB) as a part of a probably "degenerated" type I TA system (Sharma et al, 2010;Vannini et al, 2017).…”

Section: Trans-acting Regulatory Srnas Of H Pylorimentioning

confidence: 99%

“…HPnc4160 is strongly conserved in H. pylori and harbors a length-variable T stretch upstream its −10 promoter sequence. The expression of HPnc4160 was shown to be repressed by NikR in response to nickel (Eisenbart et al, 2020) through direct binding of this transcriptional regulator to the sRNA promoter (Vannini et al, 2017). Therefore, HPnc4160 was renamed NikS (Eisenbart et al, 2020).…”

Section: Trans-acting Regulatory Srnas Of H Pylorimentioning

confidence: 99%

“…The expression of HPnc4160 was shown to be repressed by NikR in response to nickel (Eisenbart et al, 2020) through direct binding of this transcriptional regulator to the sRNA promoter (Vannini et al, 2017). Therefore, HPnc4160 was renamed NikS (Eisenbart et al, 2020). The T stretch preceding the HPnc4160/NikS sRNA was variable in length in strains isolated from patients or during Mongolian gerbil colonization (Eisenbart et al, 2020;Kinoshita-Daitoku et al, 2021); this length variation affects the sRNA expression.…”

Section: Trans-acting Regulatory Srnas Of H Pylorimentioning

confidence: 99%

“…Therefore, HPnc4160 was renamed NikS (Eisenbart et al, 2020). The T stretch preceding the HPnc4160/NikS sRNA was variable in length in strains isolated from patients or during Mongolian gerbil colonization (Eisenbart et al, 2020;Kinoshita-Daitoku et al, 2021); this length variation affects the sRNA expression. Both studies identified the targets of this sRNA by mRNA and protein expression analysis.…”

Section: Trans-acting Regulatory Srnas Of H Pylorimentioning

confidence: 99%

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Riboregulation in the Major Gastric Pathogen Helicobacter pylori

Tejada-Arranz

Reuse

2021

Front. Microbiol.

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Helicobacter pylori is a Gram-negative bacterial pathogen that colonizes the stomach of about half of the human population worldwide. Infection by H. pylori is generally acquired during childhood and this bacterium rapidly establishes a persistent colonization. H. pylori causes chronic gastritis that, in some cases, progresses into peptic ulcer disease or adenocarcinoma that is responsible for about 800,000 deaths in the world every year. H. pylori has evolved efficient adaptive strategies to colonize the stomach, a particularly hostile acidic environment. Few transcriptional regulators are encoded by the small H. pylori genome and post-transcriptional regulation has been proposed as a major level of control of gene expression in this pathogen. The transcriptome and transcription start sites (TSSs) of H. pylori strain 26695 have been defined at the genome level. This revealed the existence of a total of 1,907 TSSs among which more than 900 TSSs for non-coding RNAs (ncRNAs) including 60 validated small RNAs (sRNAs) and abundant anti-sense RNAs, few of which have been experimentally validated. An RNA degradosome was shown to play a central role in the control of mRNA and antisense RNA decay in H. pylori. Riboregulation, genetic regulation by RNA, has also been revealed and depends both on antisense RNAs and small RNAs. Known examples will be presented in this review. Antisense RNA regulation was reported for some virulence factors and for several type I toxin antitoxin systems, one of which controls the morphological transition of H. pylori spiral shape to round coccoids. Interestingly, the few documented cases of small RNA-based regulation suggest that their mechanisms do not follow the same rules that were well established in the model organism Escherichia coli. First, the genome of H. pylori encodes none of the two well-described RNA chaperones, Hfq and ProQ that are important for riboregulation in several organisms. Second, some of the reported small RNAs target, through “rheostat”-like mechanisms, repeat-rich stretches in the 5′-untranslated region of genes encoding important virulence factors. In conclusion, there are still many unanswered questions about the extent and underlying mechanisms of riboregulation in H. pylori but recent publications highlighted original mechanisms making this important pathogen an interesting study model.

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Riboregulation in bacteria: From general principles to novel mechanisms of the trp attenuator and its sRNA and peptide products

Evguenieva‐Hackenberg

2021

WIREs RNA

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Gene expression strategies ensuring bacterial survival and competitiveness rely on cis‐ and trans‐acting RNA‐regulators (riboregulators). Among the cis‐acting riboregulators are transcriptional and translational attenuators, and antisense RNAs (asRNAs). The trans‐acting riboregulators are small RNAs (sRNAs) that bind proteins or base pairs with other RNAs. This classification is artificial since some regulatory RNAs act both in cis and in trans, or function in addition as small mRNAs. A prominent example is the archetypical, ribosome‐dependent attenuator of tryptophan (Trp) biosynthesis genes. It responds by transcription attenuation to two signals, Trp availability and inhibition of translation, and gives rise to two trans‐acting products, the attenuator sRNA rnTrpL and the leader peptide peTrpL. In Escherichia coli, rnTrpL links Trp availability to initiation of chromosome replication and in Sinorhizobium meliloti, it coordinates regulation of split tryptophan biosynthesis operons. Furthermore, in S. meliloti, peTrpL is involved in mRNA destabilization in response to antibiotic exposure. It forms two types of asRNA‐containing, antibiotic‐dependent ribonucleoprotein complexes (ARNPs), one of them changing the target specificity of rnTrpL. The posttranscriptional role of peTrpL indicates two emerging paradigms: (1) sRNA reprograming by small molecules and (2) direct involvement of antibiotics in regulatory RNPs. They broaden our view on RNA‐based mechanisms and may inspire new approaches for studying, detecting, and using antibacterial compounds. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Small Molecule‐RNA Interactions RNA Interactions with Proteins and Other Molecules > RNA‐Protein Complexes Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs

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A Repeat-Associated Small RNA Controls the Major Virulence Factors of Helicobacter pylori

Cited by 28 publications

References 105 publications

A bacterial small RNA regulates the adaptation of Helicobacter pylori to the host environment

A bacterial small RNA regulates the adaptation of Helicobacter pylori to the host environment

Riboregulation in the Major Gastric Pathogen Helicobacter pylori

Riboregulation in bacteria: From general principles to novel mechanisms of the trp attenuator and its sRNA and peptide products

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