Review
Copyright ©The Author(s) 2019.
World J Gastroenterol. Aug 28, 2019; 25(32): 4629-4660
Published online Aug 28, 2019. doi: 10.3748/wjg.v25.i32.4629
Table 4 A PubMed, MEDLINE and EMBASE search using the terms “Helicobacter pylori AND transcriptome OR transcriptomic” yielded 12 original research studies
StudyMain findingMethodSequencingRef.
1ObjectiveH. pylori 26695 culture grown in liquid medium to log phaseDepletion of ribosomal RNA (RiboZero, Epicentre, Illumina)Estibariz et al[107]
Characterization of the MTase JHP1050 in H. pylori
Main finding
RNA-sequencing on an Illumina HiSeq platform (Illumina, United States; 1 × 50 bp)
The MTase JHP1050, which methylates GCGC sequences, was found to be highly conserved in all analyzed H. pylori strains, with a nucleotide sequence identity > 87%. Absence of m5C methylation had a significant effect on H. pylori growth, led to a significant reduction in DNA uptake capacity, and reduced the bacterial protection against an excess of copper
2ObjectiveH. pylori 26695 culture grown in liquid medium to early log phaseRNA-sequencing on a HTSeq v0.6.1 platform[148]Han et al[114]
Analyzing the impact of bismuth on a diverse array of intracellular pathways in H. pylori
Main finding
Bismuth influences multiple metabolic pathways and suppresses energy production in H. pylori through disruption of the central carbon metabolism of the bacterium. Bismuth initially perturbs the citric acid cycle and then urease activity, followed by the induction of oxidative stress and inhibition of energy production, and in the meantime, induces extensive down-regulation in the H. pylori metabolome
3ObjectiveH. pylori grown on non-selective solid agar mediaDepletion of ribosomal RNA (RiboZero, Epicentre, Illumina) RNA-sequencing on an Illumina NextSeq platform (Illumina)Hathroubi et al[106]
Transcriptomic analysis to assess the process of biofilm formation in H. pylori
Main finding
H. pylori biofilm cells displayed a distinct transcriptomic profile. Lower metabolism and stress responses, likely associated with the microenvironment generated in the H. pylori biofilm, could be determinants of antimicrobial tolerance and involved in the persistence and survival of H. pylori. However, there were no specific genes up-or downregulated that are specific for biofilm formation, suggesting that there is no biofilm-specific set of genes expressed. However, genes encoding flagellar filaments were upregulated in biofilm cells and formed an integral part of the biofilm matrix
4ObjectiveH. pylori strain 7.13 was grown in liquid medium to mid exponential phase (OD of 0.5)Depletion of ribosomal RNA (RiboZero, Epicentre, Illumina)Loh et al[111]
Transcriptional analysis of H. pylori gene expression under high salt conditions
Main finding
Differential expression of multiple genes encoding outer membrane proteins, including adhesins (SabA, HopA and HopQ) and proteins involved in iron acquisition (FecA2 and FecA3) was observed. Transcript levels of sabA, hopA and hopQ were increased, whereas transcript levels of fecA2 and fecA3 were decreased under high-salt conditions. Functions associated with the up- and downregulated genes included acetone metabolism, acid survival, flagellar synthesis and iron transport
RNA-sequencing on an Illumina HiSeq 3000 platform (Illumina; 2 × 75 bp)
5ObjectiveH. pylori strain G27 grown in liquid medium, followed by adaptation of the pH (3.0, 4.5, 6.0, 7.4, 8.0)Depletion of ribosomal RNA (RiboZero, Epicentre, Illumina)Marcus et al[112]
Transcriptional analysis of H. pylori gene expression under different pH conditions
Main findingRNA-sequencing on an Illumina HiSeq 2500 platform (Illumina; 1 × 50 bp)
About 250 genes were induced, and an equal number of genes were repressed at acidic pH. Genes encoding for antioxidant proteins, flagellar structural proteins, type-IV secretion system (T4SS)/Cag-pathogenicity island, FoF1-ATPase, and proteins involved in acid acclimation were highly expressed at acidic pH
6ObjectiveDifferent H. pylori strains grown in liquid medium to mid exponential phase (OD = 0.7) with/without heat shock treatmentDepletion of ribosomal RNA (RiboZero, Epicentre, Illumina)Pepe et al[113]
Characterization of the heat shock protein repressor (HspR) binding sites in H. pylori
Main findingRNA-sequencing on an Illumina GAIIX platform (Illumina; 1 × 85 bp)
HspR is involved in the regulation of different crucial cellular functions through a limited number of genomic binding sites. There is high sequence conservation in the HAIR motif (an HspR-associated inverted repeat of Streptomyces spp.) among H. pylori strains. Site-directed mutagenesis demonstrated that the HAIR motif is fundamental for HspR binding and that additional nucleotide determinants flanking the HAIR motif are required for complete binding of HspR to its operator sequence spanning over 70 bp of DNA
7ObjectiveGastric biopsy specimens from patients with H. pylori infection and premalignant tissue changesDepletion of ribosomal RNA (RiboZero, Epicentre, Illumina)Thorelll et al[116]
Analysis of the composition of the transcriptionally active microbial community and H. pylori gene expression in gastric biopsy specimens from patients with H. pylori infection and premalignant tissue changes
RNA-Sequencing on an Illumina HiScanSQ platform (Illumina; 2 × 100 bp)
Main finding
Although H. pylori infection did not change the bacterial diversity, H. pylori abundance was positively correlated with the presence of Campylobacter, Deinococcus and Sulfurospirillum. Quantification of H. pylori gene expression found high expression of genes involved in pH regulation and nickel transport
8ObjectiveH. pylori strains grown in liquid medium and treated with high nickel (500 μM Ni2+) concentrationsDepletion of ribosomal RNA (RiboZero, Epicentre, Illumina)Vannini et al[115]
Characterization of the Nickel dependent transcriptional regulator (NikR) in H. pylori
Main findingRNA-sequencing on an Illumina MiSeq platform (Illumina; 1 × 76 bp)
NikR not only regulates metal-ion transporters but also virulence factors, non-coding RNAs, as well as toxin-antitoxin systems in response to nickel stimulation
9ObjectiveH. pylori strains grown to mid exponential growth phase (OD = 0.7)RNA-sequencing on an Illumina HiSeq 2000 platform (Illumina; 1 × 97 bp)Bischler et al[108]
Characterization of Nudix hydrolases in H. pylori
Main finding
H. pylori encodes two proteins resembling Nudix enzymes. One of them, HpRppH, is an RNA pyro-phosphohydrolase that triggers RNA degradation in H. pylori, whereas the other, HP0507, lacks such activity. Transcriptional analysis revealed at least 63 potential HpRppH targets in H. pylori
10ObjectiveH. pylori strains grown in liquid medium to mid exponential phase (OD of 0.5)Depletion of ribosomal RNA by a rRNA modified capture hybridization approach from MICROBExpress kit (Ambion, Invitrogen, Life Technologies)Redko et al[110]
Characterization of the exo- and endoribonuclease RNase J in H. pylori and its putative targets
Main finding
Strong depletion of RNase J led to a massive increase in the steady-state levels of non-rRNAs. mRNAs and RNAs antisense to open reading frames. In contrast, non-coding RNAs expressed in the intergenic regions were much less affected by RNase J depletion. This suggests that RNase J is a major RNase involved in degradation of most cellular RNAs in H. pylori
RNA-sequencing on an Illumina HiSeq 2000 platform (Illumina; 1 × 50 bp)
11Objective Analysis of methylated DNA sites throughout the H. pylori genome for several closely related H. pylori strainsH. pylori strains (HPYF1 and HPYF2) grown to mid exponential phase (OD of 0.4)RNA-sequencing on an Illumina HiSeq 2000 platform (Illumina)Futura et al[149]
Main finding
Overall, the methylome was highly variable among closely related H. pylori strains. DNA sequence motifs for methylation could be assigned to a specific homology group of the target recognition domains in the specificity-determining genes for Type I and other restriction-modification systems. Knocking out one of the Type I specificity genes led to transcriptome changes
12ObjectiveH. pylori grown on non-selective solid agar mediaTotal RNA was digested with DNase ISharma et al[150]
Characterization of the transcriptome of H. pylori, and construction of a genome-wide map of H. pylori transcriptional start sites and operons
RNA-sequencing was performed on a Roche 454 FLX platform (Roche, Basel, Switzerland) and on a Genome Analyzer II platform (Illumina; 1 × 76 bp)
Main finding
Discovery of hundreds of transcriptional start sites within operons, and opposite to annotated genes, indicating that complexity of gene expression from the small H. pylori genome is increased by uncoupling of polycistrons and by genome-wide antisense transcription. An unexpected number of approximately 60 small RNAs including the epsilon-subdivision counterpart of the regulatory 6S RNA and associated RNA products, and potential regulators of cis- and trans-encoded target messenger RNAs were discovered