Origin of the Diversity in DNA Recognition Domains in Phasevarion Associated modA Genes of Pathogenic Neisseria and Haemophilus influenzae

Jayde A Gawthorne,Scott A Beatson,Yogitha N Srikhanta,Kate L Fox,Michael P Jennings,Riccardo Manganelli

doi:10.1371/journal.pone.0032337

Jayde A Gawthorne, Scott A Beatson + Show 4 more

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https://doi.org/10.1371/journal.pone.0032337

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Journal: PloS one	Publication Date: Mar 23, 2012
Citations: 72	License type: CC BY 4.0

Affiliation: University of Queensland, Griffith University

Abstract

Phase variable restriction-modification (R-M) systems have been identified in a range of pathogenic bacteria. In some it has been demonstrated that the random switching of the mod (DNA methyltransferase) gene mediates the coordinated expression of multiple genes and constitutes a phasevarion (phase variable regulon). ModA of Neisseria and Haemophilus influenzae contain a highly variable, DNA recognition domain (DRD) that defines the target sequence that is modified by methylation and is used to define modA alleles. 18 distinct modA alleles have been identified in H. influenzae and the pathogenic Neisseria. To determine the origin of DRD variability, the 18 modA DRDs were used to search the available databases for similar sequences. Significant matches were identified between several modA alleles and mod gene from distinct bacterial species, indicating one source of the DRD variability was via horizontal gene transfer. Comparison of DRD sequences revealed significant mosaicism, indicating exchange between the Neisseria and H. influenzae modA alleles. Regions of high inter- and intra-allele similarity indicate that some modA alleles had undergone recombination more frequently than others, generating further diversity. Furthermore, the DRD from some modA alleles, such as modA12, have been transferred en bloc to replace the DRD from different modA alleles.

Highlights

Restriction-modification (R-M) systems are ubiquitous in bacteria and are involved in protecting the host cell from the invasion of foreign DNA [1]
Investigating the origins of the distinct modA phasevarions in Haemophilus influenzae and the pathogenic Neisseria forms the basis of this study
A further 5 distinct modA alleles have been determined through sequencing of modA genes in H. influenzae [14] and N. gonorrhoeae and N. meningitidis [19], Table 2

Summary

Introduction

Restriction-modification (R-M) systems are ubiquitous in bacteria and are involved in protecting the host cell from the invasion of foreign DNA [1]. R-M systems are comprised of two components, a methyltransferase (Mod) and a restriction endonuclease (Res). Mod catalyses the methylation of host DNA at a specific nucleotide within a defined recognition sequence, allowing for the recognition of self DNA and Res catalyses the cleavage of unmethylated DNA [2]. R-M systems are classified into four groups on the basis of subunit composition, cleavage position, sequence specificity and co-factor requirements [3]. Type I R-M systems are comprised of three subunits, S, M and R, which together form a holoenzyme that performs both methylation and restriction activity. Type II systems consist of two independently acting enzymes for methylation and restriction, each encoded by a separate gene. Type II restriction enzymes cleave DNA at very defined positions within or close to their recognition sequences, making them valuable laboratory tools [6]. Type IV systems are extremely similar to type II systems in that methylation and restriction are catalysed by independently acting enzymes but the restriction endonuclease requires a methyl donor for successful cleavage [3]

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