Regulation of the <i>Hpy</i>II restriction–modification system of <i>Helicobacter pylori</i> by gene deletion and horizontal reconstitution

Aras, Rahul; Takata, Tohru; Ando, Takafumi; Ende, Arie van der; Blaser, Martin J.

doi:10.1046/j.1365-2958.2001.02637.x

Cited by 34 publications

(44 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A diversity of MTases expressed among independent tested strains was also observed. Both the large number and the diversity are in agreement with results published elsewhere (4,5,22,43,45,48). Among the tested MTases, eight gave the same result for all tested strains: five MTases were common to all (M.BseRI, M.EagI, M.HhaI, M.NlaIII, and M.NaeI), and two MTases were absent in all strains (M.FokI and M.Sau3AI).…”

Section: Discussionsupporting

confidence: 91%

Genomic Methylation: a Tool for Typing Helicobacter pylori Isolates

Vale

Vítor

2007

Appl Environ Microbiol

View full text Add to dashboard Cite

The genome sequences of three Helicobacter pylori strains revealed an abundant number of putative restriction and modification (R-M) systems within a small genome (1.60 to 1.67 Mb). Each R-M system includes an endonuclease that cleaves a specific DNA sequence and a DNA methyltransferase that methylates either adenosine or cytosine within the same DNA sequence. These are believed to be a defense mechanism, protecting bacteria from foreign DNA. They have been classified as selfish genetic elements; in some instances it has been shown that they are not easily lost from their host cell. Possibly because of this phenomenon, the H. pylori genome is very rich in R-M systems, with considerable variation in potential recognition sequences. For this reason the protective aspect of the methyltransferase gene has been proposed as a tool for typing H. pylori isolates. We studied the expression of H. pylori methyltransferases by digesting the genomic DNAs of 50 strains with 31 restriction endonucleases. We conclude that methyltransferase diversity is sufficiently high to enable the use of the genomic methylation status as a typing tool. The stability of methyltransferase expression was assessed by comparing the methylation status of genomic DNAs from strains that were isolated either from the same patient at different times or from different stomach locations (antrum and corpus). We found a group of five methyltransferases common to all tested strains. These five may be characteristic of the genetic pool analyzed, and their biological role may be important in the host/bacterium interaction.Microorganisms with spiral morphology in human and animal stomach have been known for over a century, but for many years, the stomach environment was considered too harsh for bacteria, and those observations were neglected (11,19). After the isolation and cultivation of Helicobacter pylori from a human gastric biopsy specimen, achieved by Barry Marshall and Robin Warren in 1982, the scientific community finally accepted the idea that there are bacteria living in the human stomach (24). Soon after this important discovery, similar microorganisms were isolated from the stomachs of various wild and domestic mammals, such as cheetahs, dogs, pigs, and cats. Marshall and Warren discovered that several human gastric pathologies are induced by H. pylori (gastritis, or ulcers of the duodenum or of the stomach) and that the bacterium is associated with inflammation of the stomach mucous membrane. Later, several epidemiological studies found a strong correlation between gastric cancer and H. pylori. Since 1994, the World Health Organization has also classified H. pylori as a group 1 carcinogen (15, 41).More than half of the human population is infected with H. pylori. In North America, as well as in northern and western Europe, 5 to 15% of children and 10 to 60% of adults are infected with H. pylori. The prevalence is much higher elsewhere (3). Although only a small percentage develop disease, this is a very large number of patients.For these reasons,...

show abstract

Section: Discussionsupporting

confidence: 91%

Genomic Methylation: a Tool for Typing Helicobacter pylori Isolates

Vale

Vítor

2007

Appl Environ Microbiol

View full text Add to dashboard Cite

show abstract

“…FM991728), G27 (CP001173), and P12 (CP001217) also lack jhp0562 alleles but have ␤-(1,3)galT 5= ends similar to that of jhp0562 supports this hypothesis. Nevertheless, since H. pylori strains are naturally competent, genetic materials deleted through intragenomic recombination can be restored by transformation (7,18,47).…”

Section: Discussionmentioning

confidence: 99%

Novel Functions for Glycosyltransferases Jhp0562 and GalT in Lewis Antigen Synthesis and Variation in Helicobacter pylori

Pohl

Kienesberger

2012

Infect Immun

Self Cite

View full text Add to dashboard Cite

ABSTRACTLewis (Le) antigens are fucosylated oligosaccharides present in theHelicobacter pylorilipopolysaccharide. Expression of these antigens is believed to be important forH. pyloricolonization, since Le antigens also are expressed on the gastric epithelia in humans. A galactosyltransferase encoded by β-(1,3)galTis essential for production of type 1 (Leaand Leb) antigens. The upstream genejhp0562, which is present in many but not allH. pyloristrains, is homologous to β-(1,3)galTbut is of unknown function. BecauseH. pyloridemonstrates extensive intragenomic recombination, we hypothesized that these two genes could undergo DNA rearrangement. A PCR screen and subsequent sequence analyses revealed that the two genes can recombine at both the 5′ and 3′ ends. Chimeric β-(1,3)galT-like alleles can restore function in a β-(1,3)galTnull mutant, but neither native nor recombinantjhp0562can. Mutagenesis ofjhp0562revealed that it is essential for synthesis of both type 1 and type 2 Le antigens. Transcriptional analyses of both loci showed β-(1,3)galTexpression in all wild-type (WT) and mutant strains tested, whereasjhp0562was not expressed injhp0562null mutants, as expected. Sincejhp0562unexpectedly displayed functions in both type 1 and type 2 Le synthesis, we asked whethergalT, part of the type 2 synthesis pathway, had analogous functions in type 1 synthesis. Mutagenesis and complementation analysis confirmed thatgalTis essential for Lebproduction. In total, these results demonstrate thatgalTandjhp0562have functions that cross the expected Le synthesis pathways and thatjhp0562provides a substrate for intragenomic recombination to generate diverse Le synthesis enzymes.

show abstract

“…In silico analysis of the H. pylori genome reveals the existence of numerous, nonrandomly distributed, proximate, direct DNA repeat sequences that are "hot spots" for intragenomic DNA rearrangements (2,8,9,57). Generation of loose DNA ends, that can participate in recombination events, are believed to promote deletion and duplication of intervening sequences between such direct DNA repeats.…”

Section: Analyses Of Muts Family Homologsmentioning

confidence: 99%

Structural and Functional Divergence of MutS2 from Bacterial MutS1 and Eukaryotic MSH4-MSH5 Homologs

2005

Self Cite

View full text Add to dashboard Cite

MutS homologs, identified in nearly all bacteria and eukaryotes, include the bacterial proteins MutS1 and MutS2 and the eukaryotic MutS homologs 1 to 7, and they often are involved in recognition and repair of mismatched bases and small insertion/deletions, thereby limiting illegitimate recombination and spontaneous mutation. To explore the relationship of MutS2 to other MutS homologs, we examined conserved protein domains. Fundamental differences in structure between MutS2 and other MutS homologs suggest that MutS1 and MutS2 diverged early during evolution, with all eukaryotic homologs arising from a MutS1 ancestor. Data from MutS1 crystal structures, biochemical results from MutS2 analyses, and our phylogenetic studies suggest that MutS2 has functions distinct from other members of the MutS family. A mutS2 mutant was constructed in Helicobacter pylori, which lacks mutS1 and mismatch repair genes mutL and mutH. We show that MutS2 plays no role in mismatch or recombinational repair or deletion between direct DNA repeats. In contrast, MutS2 plays a significant role in limiting intergenomic recombination across a range of donor DNA tested. This phenotypic analysis is consistent with the phylogenetic and biochemical data suggesting that MutS1 and MutS2 have divergent functions.MutS homologs (MSH) have been identified in most prokaryotic and all eukaryotic organisms examined. Prokaryotes have two homologs (MutS1 and MutS2), whereas seven MSH proteins (MSH1 to MSH7) have been identified in eukaryotes (16,19,23). The homodimer MutS1 and heterodimers MSH2-MSH3 and MSH2-MSH6 are primarily involved in mitotic mismatch repair, whereas MSH4-MSH5 is involved in resolution of Holliday junctions during meiosis (1, 64). All members of the MutS family contain the highly conserved Walker A/B ATPase domain (16), and many share a common mechanism of action. MutS1, MSH2-MSH3, MSH2-MSH6, and MSH4-MSH5 dimerize to form sliding clamps, and recognition of specific DNA structures or lesions results in ADP/ATP exchange (27,45,49,64).The function of the second prokaryotic homolog, MutS2, is unknown. Sequence analyses reveal fundamental differences between MutS2 and other MutS family members (19). MutS2 proteins contain a conserved C-terminal domain of ϳ250 amino acid residues not found in other MutS homologs and lack the conserved N-terminal region present in most of the other MutS family members (43). According to one hypothesis, MutS2 is more closely related to the meiotic recombination proteins MSH4 and MSH5, while MutS1 is more closely related to MSH2,. This hypothesis suggests a gene duplication event early in the evolution of MutS, resulting in the two main MutS lineages, with MSH4 and MSH5 branching with MutS2 and MSH2, -3, and -6 branching with MutS1. Consistent with this hypothesis, MutS2 has been shown to not play a role in mismatch repair (13,59,69). However, arguing against this hypothesis is the lack of homology between MutS2 and MSH4-MSH5. According to another hypothesis, all eukaryotic MutS homologs evolved from one ancesto...

show abstract

Regulation of the HpyII restriction–modification system of Helicobacter pylori by gene deletion and horizontal reconstitution

Cited by 34 publications

References 52 publications

Genomic Methylation: a Tool for Typing Helicobacter pylori Isolates

Genomic Methylation: a Tool for Typing Helicobacter pylori Isolates

Novel Functions for Glycosyltransferases Jhp0562 and GalT in Lewis Antigen Synthesis and Variation in Helicobacter pylori

Structural and Functional Divergence of MutS2 from Bacterial MutS1 and Eukaryotic MSH4-MSH5 Homologs

Contact Info

Product

Resources

About