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Mobley HLT, Mendz GL, Hazell SL, editors. Helicobacter pylori: Physiology and Genetics. Washington (DC): ASM Press; 2001.

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Helicobacter pylori: Physiology and Genetics.

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Chapter 24Restriction and Modification Systems


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Prokaryotic restriction-modification (R-M) systems were first recognized in Escherichia coli nearly 50 years ago (8, 20) and are now known to be ubiquitous among bacterial species. In general, R-M systems consist of two distinct enzymatic activities: first, a restriction endonuclease that cleaves DNA at a specific recognition sequence, and second, a DNA methyltransferase that methylates DNA at the same site and thus prevents cleavage by the cognate restriction enzyme. The genomic sequences of Helicobacter pylori strains J99 and 26695 (3, 30) have revealed that this bacterium contains an abundance of restriction and modification genes, some of which have been subsequently shown to function as authentic R-M systems or as partial systems, composed of the DNA methyltransferase component alone. Interestingly, R-M genes comprise a significant percentage of H. pylori strain-specific genes (1, 3, 30) and are more prevalent in H. pylori than in other bacterial species whose genomes have been fully sequenced (29). R-M systems in H. pylori have been identified on the basis of sequence similarity to known restriction enzymes and methyltransferases, genetic organization, and specific enzyme isolation and characterization. This chapter summarizes the current state of knowledge regarding the structure and function of the large number of putative R-M genes and systems that are now recognized to be present in H. pylori.

Classification of R-M Systems

The majority of R-M systems can be classified as type I, II, IIS, or III on the basis of enzyme structure, cofactor requirements, structure of the DNA recognition site, and location of DNA cleavage relative to the recognition site (for recent reviews, see references 9, 22, and 32). In enteric bacteria, type I R-M systems have been demonstrated to be multifunctional protein complexes composed of three subunits encoded by the hsdS, hsdM, and hsdR genes. In this enzyme complex, the HsdS subunit determines the specificity of DNA sequence recognition for both the cleavage reaction catalyzed by the HsdR subunit and the methylation reaction catalyzed by the HsdM subunit. DNA cleavage occurs randomly at significant distances from an asymmetric recognition site (400 to 7,000 bp). Type II R-M systems consist of two separate proteins with independent enzymatic activities, a restriction endonuclease and a DNA methyltransferase. In contrast to type I systems, DNA cleavage or methylation occurs within symmetrical recognition sites. Type IIS R-M systems are similar to type II, except that DNA cleavage occurs at a fixed distance (1 to 20 bp) from an asymmetrical recognition site. Type III R-M systems are encoded by two contiguous structural genes, mod and res. Restriction enzyme activity is catalyzed by a complex containing both Mod and Res subunits; however, the mod gene product can function independently as a modification methylase. The Res subunit is necessary for DNA cleavage whereas the Mod subunit is required for specific DNA recognition for both restriction and methylation. DNA cleavage occurs 25 to 27 bp 3′ to an asymmetrical recognition site that is 5 to 6 bp in length.

R-M Systems Identified from Genome Sequences

Type I R-M systems

Analyses of the genome sequences of H. pylori strains 26695 and J99 revealed that each strain contains genes specifying three type I R-M systems (Table 1). The genetic organization of these systems is similar to that found in E. coli and other enteric bacteria (24), in which each subunit is encoded by contiguous hsdR, hsdM, and hsdS genes. In enteric bacteria, there are two transcriptional units, with hsdM and hsdS forming a separate operon from hsdR, which is transcribed from its own promoter. In H. pylori, nothing is known about the organization of transcriptional units for these genes, but the gene order and the direction of transcription for each of these putative type I systems have been determined from the genome sequences. For the first type I R-M system, the order of genes is hsdR1-hsdM1-hsdS1a/b and transcription of each gene is in the same direction, proceeding from hsdR1 toward hsdS1a/b; for the second type I R-M system, the gene order is hsdM2-hsdS2-hsdR2 and transcription of each gene is in the same direction, proceeding from hsdM2 toward hsdR2; and for the third type I R-M system, the gene order is hsdS3a/3b-hsdM3-hsdR3 and transcription of hsdR3 is divergent from hsdM3 and hsdS3a/b. In addition to these three potentially complete systems, these strains also contain orthologs of hsdS genes, one in strain J99 encoding HsdS4, and two in strain 26695 encoding HsdS5 and HsdS6. These genes are not linked genetically to hsdR and hsdM genes and may represent remnants of additional type I R-M systems.

Table 1. Type I R-M genes predicted from H. pylori genome sequences.

Table 1

Type I R-M genes predicted from H. pylori genome sequences.

At present, there are no data available that demonstrate that any of these type I R-M genes are expressed in H. pylori and produce functional proteins. In fact, the nucleotide sequence of the hsdR1 gene of strain J99 contains an authentic frameshift mutation, suggesting that HsdR1 may not be synthesized in this strain. However, a homopolymeric C tract (residues 605 to 614) precedes this frameshift, fostering the possibility that expression of this gene may be regulated by a slipped-strand repair mechanism (15, 26), similar to that recently described for H. pylori fucosyl transferase genes (6). Insertion of a C residue within this homopolymeric tract would result in the translation of an HsdR protein with approximately 84% amino acid identity to the predicted HsdR1 protein from strain 26695. The potential importance of these sequences for the regulation of HsdR1 synthesis in strain J99 is suggested by the fact that the same region of the hsdR1 gene from strain 26695 also contains a homopolymeric C tract (residues 614 to 628).

The level of amino acid identity of individual HsdR or HsdM proteins between strains 26695 and J99 is high, ranging from 82 to 92% (Table 1). However, alignment of the predicted amino acid sequences of the three different HsdR proteins (R1, R2, R3) or the three different HsdM proteins (M1, M2, M3) in either strain reveals some regions of sequence homology, but a low overall level of identity, suggesting that each set of HsdR and HsdM proteins represents different type I families (24). The HsdS subunit of type I R-M systems determines the DNA sequence specificity for both restriction and modification reactions. The HsdS proteins (S1, S2, S3) in either strain share no significant amino acid homology to each other. On the other hand, alignment of the predicted amino acid sequences of HsdS1a and HsdS1b reveals nearly 100% identity for the 180 N-terminal amino acid residues with a significant level of C-terminal sequence divergence, which is consistent with allelic genes that impart differing DNA recognition specificity. The small sizes of HsdS3b and HsdS6 make it unlikely that these proteins function as specificity determinants in H. pylori strain 26695, but this function may be provided by HsdS5. The J99 HsdS2 protein shows 93% sequence identity to the 199 C-terminal residues of the 26695 HsdS2 protein and, thus, resembles an N-terminal truncation of that S protein. Finally, in strain J99 the HsdS4 protein shares amino acid sequence homology with the other HsdS proteins in this strain and, therefore, may associate with the various HsdR and HsdM subunit pairs to produce additional type I systems with different DNA recognition specificities.

Type II and IIS R-M systems

Type II and IIS R-M systems are generally encoded by contiguous genes and, unlike type I and III R-M systems, are composed of independent restriction endonuclease and methyltransferase enzymes. Analyses of the genome sequences of strains 26695 and J99 suggest that H. pylori contains a plethora of genes with homology to known type II and IIS R-M genes (Table 2). Approximately 40% of these genes are able to express functional type II/IIS R-M proteins in H. pylori. A total of 11 putative methyltransferase genes, either shared or strain specific, that do not have an identifiable companion gene encoding a cognate restriction endonuclease are shown in Table 2. In addition, restriction endonuclease function is absent as a consequence of translational frameshift mutations in R-M systems such as the MboI-M.MboI homolog in strain J99, and the NlaIII-M.NlaIII homolog in strain 26695 in which the gene encoding the restriction endonuclease is present. These observations suggest that there is either a selective advantage for H. pylori to retain specific methyltransferase function or no selective advantage to retain the companion restriction endonuclease of a particular R-M system. Besides numerous methyltransferase genes, strains 26695 and J99 contain four complete, functional R-M systems, which differ in each strain, and four shared R-M systems that have not yet been characterized or shown to encode functional proteins (see also Table 4). The expression of the restriction endonuclease component of one of these uncharacterized R-M systems (HP1471/JHP1364) may be regulated by a slipped-strand repair mechanism involving a homopolymeric G tract in the coding sequence. Finally, strain 26695 contains the complete type IIS MboII R-M system, while in strain J99 only the 3′ end of the gene encoding the MboII homolog is present (3, 7).

Table 2. Type II R-M genes predicted from H. pylori genome sequences.

Table 2

Type II R-M genes predicted from H. pylori genome sequences.

Table 4. Type II and IIS restriction enzymes isolated from various H. pylori strains.

Table 4

Type II and IIS restriction enzymes isolated from various H. pylori strains.

Nonclassical R-M systems

Two R-M systems, identified from the genome sequence of strain 26695, have biochemical properties significantly different from the classical R-M systems (Table 2). The first one is the genetic locus HP0452, which encodes a putative protein with homology to Methanobacterium McrB. This type of restriction system does not have a modification component and is composed solely of a restriction endonuclease that cleaves DNA in specific sequence contexts that contain methylcytosine (24). The second nonclassical R-M system is gene HP1517, which encodes a putative protein with homology to E. coli Eco57I. Eco57I is a bifunctional protein with both restriction endonuclease and methylase activities (18). It has been proposed that the Eco57I R-M system, which also includes a separate methyltransferase, be classified as type IV (18). Neither of these R-M systems is present in strain J99.

Type III R-M systems

H. pylori strains 26695 and J99 each contain genes orthologous to functional type III R-M systems in E. coli and Salmonella (24). Strain 26695 contains three different type III R-M systems, and strain J99 contains two (Table 3). One of the type III R-M systems (res-2/mod-2) is shared by both strains, and the Res subunits exhibit 85% amino acid identity. In both strains the mod-2 gene contains a frameshift mutation within the open reading frame (ORF). Similar to several other R-M genes in H. pylori, expression of this gene may be regulated by a slipped-strand repair mechanism, as a homopolymeric G tract is present in mod-2 preceding the translational frameshift, residues 1326 to 1337 in 26695 and residues 1323 to 1333 in J99. In this tract of mod-2, addition of a G residue to the gene of strain 26695 or subtraction of a G residue from the gene of strain J99 would result in the synthesis of full-length proteins sharing 75% amino acid identity. Since type III R-M systems function as heterodimeric complexes composed of Res and Mod subunits and the Res subunit alone does not have enzymatic activity, expression of Res-2 in the absence of Mod-2 would not be expected to be detrimental to the host cell. In strain 26695, genetic loci HP1369 and HP1370 probably encode the respective N-terminal and C-terminal segments of Mod4. Inspection of the nucleotide sequence suggests that the Mod4 ORF prematurely terminates downstream of a homopolymeric G tract in HP1369 (residues 1402 to 1411). The addition of one G residue to this tract would allow in-frame translation to the end of HP1370, resulting in the synthesis of a 93.9-kDa Mod4 protein.

Table 3. Type III R-M genes predicted from H. pylori genome sequences.

Table 3

Type III R-M genes predicted from H. pylori genome sequences.

Expression of functional type III R-M systems has not yet been demonstrated in H. pylori. The apparent requirement for slipped-strand repair of frameshift mutations in mod-2 and mod-4 suggests that these two putative type III systems may not be expressed. De Vries et al. recently demonstrated mod transcription using a lacZ fusion in a mod gene of H. pylori strain 1061, and reported that expression of this gene was subject to on-off switching at the transcriptional level (11). The res gene in strain 1061 is located immediatedly upstream of mod and contains a homopolymeric C tract within the Res ORF. Variations in the length of this C tract, affecting translation of a full-length Res protein, were found to be linked to phase-variable mod transcription (11). H. pylori strain 1061 mod is homologous to mod-1 from strain J99 (JHP1296) (de Vries, personal communication), but strain J99 res-1 (JHP1297), located upstream of mod-1, does not contain a homopolymeric C tract within the Res ORF (3), suggesting that expression of this type III R-M system in strain J99 may be regulated differently from the type III system in strain 1061.

Functional R-M Systems

Functional type I and type III R-M systems have not been identified in H. pylori. Table 4 lists the functional type II/IIS restriction enzymes that have been isolated from various H. pylori strains (17, 25, 33, 35). A total of 26 different restriction endonucleases with unique recognition specificities from 14 H. pylori strains are shown. Fifteen restriction endonucleases were isolated from multiple strains. All but three of the enzymes are isoschizomers, that is, restriction endonucleases from different bacterial species that recognize the same sequence of known restriction enzymes. In addition to the restriction endonucleases in Table 4, isoschizomers of restriction endonucleases AsuI, FnuDII, NlaIV, SduI, and SfeI have also been isolated from several H. pylori RFL strains (MBI Fermentas) not listed in the table (25). The three restriction enzymes with unique recognition specificity were each isolated from a different Nashville, Tenn., strain and subsequently identified in other strains from diverse geographic areas (Table 4). Hpy99I was initially isolated from strain J99 and later an isoschizomer of this enzyme was isolated from the Lithuanian strain RFL61 (25). Hpy178III was isolated from strain J178, and isoschizomers of this enzyme were subsequently isolated from strains J188, CH4, and several different RFL strains (25, 33). Hpy188I was isolated from strain J188, and subsequently isoschizomers were isolated from strain J166 and 12 different RFL strains (25, 33, 35). Later, it was found that the genes encoding the Hpy188I R-M system were integrated in the same chromosomal region in strains J188 and J166 (35).

The presence of a given restriction endonuclease in a strain indicates that the cognate methyltransferase also must be present and functional to protect endogenous DNA from cleavage. The converse is not true; a specific methyltransferase activity can persist in a strain in the absence of the cognate restriction endonuclease. H. pylori contains numerous putative methyltransferase genes, many of which are not paired with genes encoding a companion restriction endonuclease. This observation is supported by the data presented in Table 5 that show the prevalence and diversity of various methyltransferase activities in 19 different H. pylori strains, as determined by resistance of genomic DNA to digestion by the cognate restriction enzyme (5). These results indicate that numerous methyltransferases are expressed by H. pylori strains, and that the complement of expressed methyltransferases differs greatly between strains. This conclusion was supported by the results of another study in which the activity of additional methyltransferases in various H. pylori strains was examined (33). For many of the methyltransferases listed in Table 5 it is not known whether the cognate restriction endonuclease is also present, but as indicated from the genome sequences, it is probable that the restriction endonuclease component of some of these potential R-M systems is either absent or nonfunctional. For example, all strains examined express the M. HpyI adenine methyltransferase that modifies the sequence CATG (M.NlaIII homolog) (5), but the majority of the strains do not express the companion restriction enzyme, HpyCH4I (iceA1) (14). In addition, strain J99 expresses methyltransferase activity homologous to M. MboI (5) but contains three translational frameshift mutations in the ORF encoding the MboI homolog and therefore most likely does not express this enzyme (3).

Table 5. Type II DNA methyltransferase activity in 19 H. pylori strainsa.

Table 5

Type II DNA methyltransferase activity in 19 H. pylori strainsa.

Role of R-M Systems in Horizontal Gene Transfer

A postulated function of R-M systems is protection of the cell from bacteriophage infection or invasion by foreign plasmid or genomic DNA; consequently, these systems appear to be involved in the maintenance of genomic integrity. Since there have only been two reports of H. pylori-specific bacteriophage (16, 27), the relative importance of R-M systems as a protective mechanism against phage infection remains uncertain, although many H. pylori strains are naturally competent for transformation by free chromosomal and plasmid DNA. It is apparent from the information available that H. pylori contains a large number of R-M systems and that the complements of these systems vary considerably between strains. Thus, foreign DNA, either from another bacterial species or a heterologous H. pylori strain, that enters the cell via natural transformation most likely will not possess the methylation pattern characteristic of the host cell DNA and will be susceptible to cleavage by resident restriction endonucleases. It has been suggested that restriction of incoming DNA may actually facilitate recombination by generating recombinogenic, double-stranded breaks in homologous donor DNA (21, 28). Therefore, enhancement of homologous recombination through the activity of R-M systems may be beneficial to H. pylori as an adaptive mechanism. The presence of a large and unique complement of R-M systems may ultimately provide some selective advantage to H. pylori in its natural environment but also presents a substantial obstacle to researchers attempting to genetically manipulate this organism (5, 12).


Analyses of the genome sequences of strains 26695 and J99 have revealed that 6 to 7% of the coding capacity of each strain are strain-specific genes, and more than half of these genes with functional orthologs in other bacterial species were predicted to encode R-M enzymes (3, 30). This prediction was subsequently supported by studies of genetic variation among H. pylori strains (1), and essentially confirmed when eight different, type II/IIS restriction endonucleases were isolated from the two sequenced strains (Table 4). With the exception of Hpy991, which is unique to H. pylori, each of these restriction endonucleases is highly homologous to prototype restriction endonucleases from other bacterial species. In general, H. pylori R-M genes occupy discrete regions of the chromosome that exhibit the greatest degree of genetic variability between strains (4) and which are usually characterized by a lower (G + C)% content than the overall genome (3). Together, these observations strongly suggest that H. pylori acquired the majority of its R-M genes from other bacterial species through horizontal gene transfer.

H. pylori apparently possesses a much greater number of R-M genes than other bacterial species whose genomes have been sequenced (29) and, as shown in Tables 4 and 5, many of these genes encode functional R-M proteins. It is unknown what, if any, selective advantage these numerous and diverse systems afford H. pylori in its natural environment. In an organism that is naturally competent for transformation by exogenous DNA, these systems may function in self/non-self recognition and protect against genomic adulteration by foreign DNA. Simultaneously, these same systems may promote homologous recombination of species-specific or closely related DNA, and thereby provide H. pylori a more rapid mechanism of genetic adaptation than de novo mutation. Rapid adaptation may be essential for an organism that colonizes a potentially hostile niche, such as the human stomach, and therefore necessary to sustain long-term infection. However, since H. pylori may readily acquire genes from its environment, it is also possible that once an R-M system establishes itself in the genome it assures its own perpetuation as a "selfish DNA element" by virtue of its DNA endonucleolytic and modifying properties (19) and therefore provides no particular benefit to its host cell.

Finally, in addition to the various R-M systems demonstrated in H. pylori, there are several examples of specific methyltransferase expression in the absence of the cognate restriction endonuclease. This observation has led to speculation that H. pylori may use site-specific methylation for the regulation of gene transcription or DNA replication. The observations that M. HpyI methyltransferase function is conserved in all the strains examined (5, 33, 34) and that hpyIM transcription is regulated by gastric epithelial cell contact (13, 23) support the hypothesis that site-specific methylation may be involved in the control of expression of genes involved in virulence and/or host cell interactions.


We thank Dawn Israel for helpful discussions and careful reading of this manuscript. This work was supported by National Institutes of Health grants R01-AI37659 and K08-DK02381.


Akopyants N. S., Fradkov A., Diatchenko L., Hill J. E., Siebert P. D., Lukyanov S. A., Sverdlov E. D., Berg D. E. PCR-based subtractive hybridization and differences in gene content among strains of Helicobacter pylori. Proc. Natl. Acad. Sci. USA. 1998;95:13108–13113. [PMC free article: PMC23726] [PubMed: 9789049]
Akopyants N. S., Jiang Q., Taylor D. E., Berg D. E. Corrected identity of isolates of Helicobacter pylori reference strain NCTC11637. Helicobacter. 1997;2:48–52. [PubMed: 9432323]
Alm R. A., Ling L. S. L., Moir D. T., King B. L., Brown E. D., Doig P. C., Smith D. R., Noonan B., Guild B. C., deJonge B. L., Carmel G., Tummino P. J., Caruso A., Uria-Nickelsen M., Mills D. M., Ives C., Gibson R., Merberg D., Mills S. D., Jiang Q., Taylor D. E., Vovis G. F., Trost T. J. Genomic-sequence comparison of two unrelated isolates of the human gastric pathogen Helicobacter pylori. Nature. 1999;397:176–180. [PubMed: 9923682]
Alm R. A., Trust T. J. Analysis of the genetic diversity of Helicobacter pylori: the tale of two genomes. J. Mol. Med. 1999;77:834–846. [PubMed: 10682319]
Ando T., Xu Q., Torres M., Kusugami K., Israel D. A., Blaser M. J. Restriction-modification system differences in Helicobacter pylori are a barrier to interstrain plasmid transfer. Mol. Microbiol. 2000;37:1052–1065. [PubMed: 10972824]
Appelmelk B. J., Martin S. L., Monteiro M. A., Clayton C. A., McColm A. A., Zheng P., Verboom T., Maaskant J. J., van den Eijnden D. H., Hokke C. H., Perry M. B., Vanden-broucke-Grauls C. M., Kusters J. G. 1999Phase variation in Helicobacter pylori lipopolysaccharide due to changes in the lengths of poly(C) tracts in alpha3-fucosyltransferase genes Infect. Immun 675361–5366.. (Erratum, 67:6715.) [PMC free article: PMC96892] [PubMed: 10496917]
Aras, R., and M. J. Blaser. 2000. Conservation of a type IIS restriction-modification system in Helicobacter pylori with homology to the MboII R-M system in Moraxella bovis, abstr. D-279, p. 290. In Abstr. 100th Gen. Meet. Am. Soc. Microbiol. 2000. American Society for Microbiology, Washington, D.C.
Bertani G., Weigle J. J. Host controlled variation in bacterial viruses. J. Bacteriol. 1953;65:113–121. [PMC free article: PMC169650] [PubMed: 13034700]
Bickle T. A., Kruger D. H. Biology of DNA restriction. Microbiol. Rev. 1993;57:434–450. [PMC free article: PMC372918] [PubMed: 8336674]
Cover T. L., Tummuru M. K., Cao P., Thompson S. A., Blaser M. J. Divergence of genetic sequences for the vacuolating cytotoxin among Helicobacter pylori strains. J. Biol. Chem. 1994;269:10566–10573. [PubMed: 8144644]
de Vries N., Duinsbergen D., Kuipers E. J., Wiesenekker P., Vandenbroucke-Grauls C. M., Kusters J. G. Phase variation in a type III restriction-modification system of Helicobacter pylori. Gastroenterology. 2000;118:A736.
Donahue J. P., Israel D. A., Peek, Jr R. M., Blaser M. J., Miller G. G. Overcoming the restriction barrier to plasmid transformation of Helicobacter pylori. Mol. Microbiol. 2000;37:1066–1074. [PubMed: 10972825]
Donahue J. P., Peek, Jr R. M., van Doorn L.-J., Thompson S. A., Xu Q., Blaser M. J., Miller G. G. Analysis of iceA1 transcription in Helicobacter pylori. Helicobacter. 2000;5:1–12. [PMC free article: PMC2779704] [PubMed: 10672045]
Figueiredo C., Quint W. G., Sanna R., Sablon E., Donahue J. P., Xu Q., Miller G. G., Peek R. M., Blaser M. J., van Doorn L.-J. Genetic organization and heterogeneity of the iceA locus of Helicobacter pylori. Gene. 2000;246:59–68. [PubMed: 10767527]
Foster P. L., Trimarchi J. M. Adaptive reversion of a frameshift mutation in Escherichia coli by simple base deletions in homopolymeric runs. Science. 1994;265:407–409. [PMC free article: PMC2990682] [PubMed: 8023164]
Heintschel von Heinegg E., Nalik H. P., Schmid E. N. Characterization of a Helicobacter pylori phage (HP1) J. Med. Microbiol. 1993;38:245–249. [PubMed: 8474115]
Ivic A., Jakeman K. J., Penn C. W., Brown N. L. Type II restriction endonucleases from Helicobacter pylori include an enzyme with a novel recognition sequence. FEMS Microbiol. Lett. 1999;179:175–180. [PubMed: 10481103]
Janulaitis A., Petrusyte M., Maneliene Z., Klimasauskas S., Butkus V. Purification and properties of the Eco57I restriction endonuclease and methylase-prototypes of a new class (type IV) Nucleic Acids Res. 1992;20:6043–6049. [PMC free article: PMC334471] [PubMed: 1334260]
Kobayashi I., Nobusato A., Kobayashi-Takahashi N., Uchiyama I. Shaping the genome-restriction-modification systems as mobile genetic elements. Curr. Opin. Genet. Dev. 1999;9:649–656. [PubMed: 10607611]
Kong H., Lin L.-F., Porter N., Stickel S., Byrd D., Posfai J., Roberts R. J. Functional analysis of putative restriction-modification system genes in the Helicobacter pylori J99 genome. Nucleic Acids Res. 2000;28:3216–3223. [PMC free article: PMC110709] [PubMed: 10954588]
Luria S. E., Human M. L. A nonhereditary, host-induced variation of bacterial viruses. J. Bacteriol. 1952;64:557–569. [PMC free article: PMC169391] [PubMed: 12999684]
McKane M., Milkman R. Transduction, restriction and recombination patterns in Escherichia coli. Genetics. 1995;139:35–43. [PMC free article: PMC1206332] [PubMed: 7705636]
Murray N. E. Type I restriction systems: sophisticated molecular machines (a legacy of Bertani and Weigle) Microbiol. Mol. Biol. Rev. 2000;64:412–434. [PMC free article: PMC98998] [PubMed: 10839821]
Peek R. M. Jr.,, Thompson S. A., Donahue J. P., Tham K. T., Atherton J. C., Blaser M. J., Miller G. G. Adherence to gastric epithelial cells induces expression of a Helicobacter pylori gene, iceA, that is associated with clinical outcome. Proc. Assoc. Am. Phys. 1998;110:531–544. [PubMed: 9824536]
Redaschi, N., and T. A. Bickle. 1996. DNA restriction and modification systems, p. 773–781. In F. C. Neidhardt (ed.), Escherichia coli and Salmonella: Cellular and Molecular Biology, 2nd ed. ASM Press, Washington, D.C.
Roberts R. J., Macelis D. REBASE—restriction enzymes and methylases. Nucleic Acids Res. 2000;28:306–307. [PMC free article: PMC102482] [PubMed: 10592256]
Rosenberg S. M., Longerich S., Gee P., Harris R. S. Adaptive mutation by deletions in small mononucleotide repeats. Science. 1994;265:405–407. [PubMed: 8023163]
Schmid E. N., von Recklinghausen G., Ansorg R. Bacteriophages in Helicobacter (Campylobacter) pylori. J. Med. Microbiol. 1990;32:101–104. [PubMed: 2355390]
Smith G. R. Mechanism and control of homologous recombination in Escherichia coli. Annu. Rev. Genet. 1987;21:179–201. [PubMed: 3327462]
The Institute for Genomic Research. 2000. http://www​
Tomb J.-F., White O., Kerlavage A. R., Clayton R. A., Sutton G. G., Fleischmann R. D., Ketchum K. A., Klenk H. P., Gill S., Dougherty B. A., Nelson K., Quackenbush J., Zhou L. X., Kirkness E. F., Peterson S., Loftus B., Richardson D., Dodson R., Khalak H. G., Glodek A., McKenney K., Fitzegerald L. M., Lee N., Adams M. D., Hickey E. K., Berg D. E., Gocayne J. D., Utterback T. R., Peterson J. D., Kelley J. M., Cotton M. D., Weidman J. M., Fujii C., Bowman C., Watthey L., Wallin E., Hayes W. S., Borodovsky M., Karp P. D., Smith H. O., Fraser C. M., Venter J. C. The complete genome sequence of the gastric pathogen Helicobacter pylori. Nature. 1997;388:539–547. [PubMed: 9252185]
Tsuda M., Karita M., Nakazawa T. Genetic transformation in Helicobacter pylori. Microbiol. Immunol. 1993;37:85–89. [PubMed: 8474363]
Vitkute J., Stankevicius K., Tamulaitiene G., Maneliene Z., Timinskas A., Berg D. E., Janulaitis A. Specificities of eleven different DNA methyltransferases of Helicobacter pylori strain 26695. J. Bacteriol. 2001;183:443–450. [PMC free article: PMC94898] [PubMed: 11133936]
Wilson G. G., Murray N. E. Restriction and modification systems. Annu. Rev. Genet. 1991;25:585–627. [PubMed: 1812816]
Xu Q., Morgan R. D., Roberts R. J., Blaser M. J. Identification of type II restriction and modification systems in Helicobacter pylori reveals their substantial diversity among strains. Proc. Natl. Acad. Sci. USA. 2000;97:9671–9676. [PMC free article: PMC16923] [PubMed: 10944229]
Xu Q., Peek R. M., Miller G. G., Blaser M. J. The Helicobacter pylori genome is modified at CATG by the product of hpyIM. J. Bacteriol. 1997;179:6807–6815. [PMC free article: PMC179612] [PubMed: 9352933]
Xu Q., Stickel S., Roberts R. J., Blaser M. J., Morgan R. D. Purification of the novel endonuclease, Hpy1881, and cloning of its restriction-modification genes reveal evidence of its horizontal transfer to the Helicobacter pylori genome. J. Biol. Chem. 2000;275:17086–17093. [PubMed: 10748211]
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