High allelic diversity in the methyltransferase gene of a phase variable type III restriction-modification system has implications for the fitness of Haemophilus influenzae

Bayliss, Christopher D.; Callaghan, Martin J.; Moxon, E. Richard

doi:10.1093/nar/gkl568

Cited by 39 publications

(38 citation statements)

References 44 publications

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“…The biological significance of changing the specificity of the NgoAV system remains unknown, but 916 sites are predicted for NgoAV in the N. gonorrhoeae genome, and only 340 sites would be recognized by NgoAV⌬. The genome is certainly undermethylated in NgoAV⌬-expressing bacteria, and the expression of many different genes may be affected, as has been demonstrated for type III RM systems (6,15,20,41). In addition, PV of RM systems may aid phage defense (6).…”

Section: Discussionmentioning

confidence: 99%

“…The genome is certainly undermethylated in NgoAV⌬-expressing bacteria, and the expression of many different genes may be affected, as has been demonstrated for type III RM systems (6,15,20,41). In addition, PV of RM systems may aid phage defense (6). Phages evolve in response to host defense mechanisms and may acquire resistance to one RM system.…”

Section: Discussionmentioning

confidence: 99%

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Deletion of One Nucleotide within the Homonucleotide Tract Present in the hsdS Gene Alters the DNA Sequence Specificity of Type I Restriction-Modification System NgoAV

2011

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As a result of a frameshift mutation, the hsdS locus of the NgoAV type IC restriction and modification (RM) system comprises two genes, hsdS NgoAV1 and hsdS NgoAV2 . The specificity subunit, HsdS NgoAV , the product of the hsdS NgoAV1 gene, is a naturally truncated form of an archetypal specificity subunit (208 N-terminal amino acids instead of 410). The presence of a homonucleotide tract of seven guanines (poly[G]) at the 3 end of the hsdS NgoAV1 gene makes the NgoAV system a strong candidate for phase variation, i.e., stochastic addition or reduction in the guanine number. We have constructed mutants with 6 guanines instead of 7 and demonstrated that the deletion of a single nucleotide within the 3 end of the hsdS NgoAV1 gene restored the fusion between the hsdS NgoAV1 and hsdS NgoAV2 genes. We have demonstrated that such a contraction of the homonucleotide tract may occur in vivo: in a Neisseria gonorrhoeae population, a minor subpopulation of cells appeared to have only 6 guanines at the 3 end of the hsdS NgoAV1 gene. Escherichia coli cells carrying the fused gene and expressing the NgoAV⌬ RM system were able to restrict phage at a level comparable to that for the wild-type NgoAV system. NgoAV recognizes the quasipalindromic interrupted sequence 5-GCA(N 8 )TGC-3 and methylates both strands. NgoAV⌬ recognizes DNA sequences 5-GCA(N 7 )GTCA-3 and 5-GCA(N 7 )CTCA-3, although the latter sequence is methylated only on the complementary strand within the 5-CTCA-3 region of the second recognition target sequence.Restriction and modification (RM) systems are composed of two enzymatic activities that recognize the same specific DNA sequence. The restriction endonuclease cleaves the DNA, unless the recognized sequence is methylated by the modification methylase. RM systems are found in a wide variety of bacteria and archaea, and their main role is to protect cells from bacteriophage infections or the uptake of undesirable foreign DNA (7, 33). The importance of RM systems in host protection is difficult to estimate in the case of bacteria for which no phages or no phage detection methods are known and that encode several RM systems, such as Neisseria gonorrhoeae (43,34). Recently, a new role for RM systems as factors regulating other gene expression was proposed for type III RM systems (16,42).Type I DNA RM systems are multimeric enzyme complexes that recognize and methylate an adenine residue within a specific DNA sequence. The cleavage of double-stranded DNA takes place at an undefined region, several hundreds to thousands of base pairs away from the recognized sequence. The archetypal type I methyltransferases are encoded by two genes, hsdS and hsdM, and are composed of one HsdS subunit and two HsdM subunits. The HsdS subunit is responsible for recognition and binding of DNA by the enzymatic complex and for the interaction of the other subunits of the enzyme. The

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Deletion of One Nucleotide within the Homonucleotide Tract Present in the hsdS Gene Alters the DNA Sequence Specificity of Type I Restriction-Modification System NgoAV

2011

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“…The effectiveness of RM systems in host protection against phage infection has been demonstrated in various studies reporting 10-to 10 8 -fold protection against phage infection (reviewed in reference 34). Interestingly, the expression of many RM systems is phase variable (35)(36)(37)(38), which has important evolutionary implications, which are discussed below.…”

Section: Restriction-modificationmentioning

confidence: 99%

“…6). However, phase variation of RM systems may allow the uptake of beneficial DNA by bacteria in which the RM system is switched off (35). That said, there is some evidence that even the CRISPR-Cas system may restrain horizontal gene transfer.…”

Section: Figmentioning

confidence: 99%

Evolutionary Ecology of Prokaryotic Immune Mechanisms

Houte

Buckling

Westra

2016

Microbiol Mol Biol Rev

223

177

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SUMMARYBacteria have a range of distinct immune strategies that provide protection against bacteriophage (phage) infections. While much has been learned about the mechanism of action of these defense strategies, it is less clear why such diversity in defense strategies has evolved. In this review, we discuss the short- and long-term costs and benefits of the different resistance strategies and, hence, the ecological conditions that are likely to favor the different strategies alone and in combination. Finally, we discuss some of the broader consequences, beyond resistance to phage and other genetic elements, resulting from the operation of different immune strategies.

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“…Of the 296 independently isolated strains, 206 were available for laboratory studies. These included 52 pediatric isolates of diverse sources used in an earlier study (11), 25 of the 27 otitis isolates from Finland that were used to develop the H. influenzae MLST scheme and have been used in several other studies (2,7,28,35), 88 isolates submitted to the Active Bacterial Core Surveillance program at the Centers for Disease Control and Prevention that had been used to develop the 16S typing system (46), and several isolates for which partial genome sequences have recently been reported. All strains were confirmed to be H. influenzae based on the requirement for ␤-NAD ϩ and hemin and were judged not to be H. haemolyticus based on recently described criteria (37).…”

Section: Phylogenetic Analysis (I) Mlstmentioning

confidence: 99%

Analysis of Genetic Relatedness of Haemophilus influenzae Isolates by Multilocus Sequence Typing

et al. 2008

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The gram-negative bacterium Haemophilus influenzae is a human-restricted commensal of the nasopharynx that can also be associated with disease. The majority of H. influenzae respiratory isolates lack the genes for capsule production and are nontypeable (NTHI). Whereas encapsulated strains are known to belong to serotype-specific phylogenetic groups, the structure of the NTHI population has not been previously described. A total of 656 H. influenzae strains, including 322 NTHI strains, have been typed by multilocus sequence typing and found to have 359 sequence types (ST). We performed maximum-parsimony analysis of the 359 sequences and calculated the majority-rule consensus of 4,545 resulting equally most parsimonious trees. Eleven clades were identified, consisting of six or more ST on a branch that was present in 100% of trees. Two additional clades were defined by branches present in 91% and 82% of trees, respectively. Of these 13 clades, 8 consisted predominantly of NTHI strains, three were serotype specific, and 2 contained distinct NTHI-specific and serotype-specific clusters of strains. Sixty percent of NTHI strains have ST within one of the 13 clades, and eBURST analysis identified an additional phylogenetic group that contained 20% of NTHI strains. There was concordant clustering of certain metabolic reactions and putative virulence loci but not of disease source or geographic origin. We conclude that well-defined phylogenetic groups of NTHI strains exist and that these groups differ in genetic content. These observations will provide a framework for further study of the effect of genetic diversity on the interaction of NTHI with the host.Haemophilus influenzae is a small (1 to 2 m in length) gram-negative bacterium that is found only in humans. The polysaccharide-protein conjugate vaccines against serotype b H. influenzae have almost eliminated H. influenzae as a cause of pediatric meningitis in the western world. However, unencapsulated (nontypeable) H. influenzae (NTHI) remains an important pathogen, particularly in children and the elderly (5,8,23). NTHI infections are usually limited to respiratory mucosal sites such as the middle ear or bronchi but are occasionally systemic. It is not known whether NTHI isolates associated with localized or systemic disease are genetically distinct from each other or distinct from isolates associated with asymptomatic colonization of the nasopharynx.Efforts to understand and control NTHI disease have been hampered by the diversity of these bacteria. Many of the surface antigens that have been studied display interstrain and intrastrain heterogeneity as a result of both sequence divergence and phase variation. It is increasingly recognized that NTHI isolates also vary in genetic content. We use the term island to refer to a genetic locus (one or more genes) that occurs in some but not all strains. As used here, the term does not imply that the locus is known to be readily transferred between strains or is thought to have been recently acquired. Islands whose functi...

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High allelic diversity in the methyltransferase gene of a phase variable type III restriction-modification system has implications for the fitness of Haemophilus influenzae

Cited by 39 publications

References 44 publications

Deletion of One Nucleotide within the Homonucleotide Tract Present in the hsdS Gene Alters the DNA Sequence Specificity of Type I Restriction-Modification System NgoAV

Deletion of One Nucleotide within the Homonucleotide Tract Present in the hsdS Gene Alters the DNA Sequence Specificity of Type I Restriction-Modification System NgoAV

Evolutionary Ecology of Prokaryotic Immune Mechanisms

Analysis of Genetic Relatedness of Haemophilus influenzae Isolates by Multilocus Sequence Typing

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