Elsevier

Plasmid

Volume 54, Issue 3, November 2005, Pages 191-218
Plasmid

Review
Comparative overview of the genomic and genetic differences between the pathogenic Neisseria strains and species

https://doi.org/10.1016/j.plasmid.2005.04.005Get rights and content

Abstract

The availability of complete genome sequences from multiple pathogenic Neisseria strains and species has enabled a comprehensive survey of the genomic and genetic differences occurring within these species. In this review, we describe the chromosomal rearrangements that have occurred, and the genomic islands and prophages that have been identified in the various genomes. We also describe instances where specific genes are present or absent, other instances where specific genes have been inactivated, and situations where there is variation in the version of a gene that is present. We also provide an overview of mosaic genes present in these genomes, and describe the variation systems that allow the expression of particular genes to be switched ON or OFF. We have also described the presence and location of mobile non-coding elements in the various genomes. Finally, we have reviewed the incidence and properties of various extra-chromosomal elements found within these species. The overall impression is one of genomic variability and instability, resulting in increased functional flexibility within these species.

Introduction

A genome sequence is a single time-point snapshot of a subculture, of a strain, of a species of bacteria, and is inherently a singular example of a complete bacterial system. However, once multiple sequences become available for comparative analysis, and once the genome sequence characteristics as a whole can be considered in the light of existing experimental data for a species, a much deeper and more informative picture can be perceived.

The pathogenic Neisseria species: Neisseria meningitidis and Neisseria gonorrhoeae are important human pathogens, being the principal causes of bacterial meningitis and gonorrhoea, respectively. These species have been the subject of intense study over many years by a substantial research community, based upon their medical disease significance. There are therefore many informative studies that can be drawn upon, tested against, and reconsidered in the light of the complete genome sequences. In this context, these sequences in addition to serving as research resources in their own right, also provide an important framework for understanding neisserial biology and for the design and construction of future experiments.

Section snippets

Neisserial sequences available

There are now four complete pathogenic Neisseria spp. genome sequences publicly available. The first two sequences were essentially completed at the same time. The first of these to be published was of N. meningitidis serogroup B strain MC58 (Tettelin et al., 2000), composed of 2,272,351 base pairs, with 2158 annotated coding sequences. The second was of N. meningitidis serogroup A strain Z2491 (Parkhill et al., 2000), with 2,184,406 base pairs and 2121 annotated coding sequences of which 1968

Identified islands

Unlike many other bacterial species, no classical Pathogenicity Islands with characteristic adjacent tRNA loci, flanking direct repeats, foreign DNA signatures, and virulence genes (Blum et al., 1994, Hacker et al., 1990) have been found in the Neisseria spp. There are, however, a number of large regions with foreign DNA characteristics of divergent % GC and nucleotide signatures that differ between strains MC58 and Z2491, which have been called Islands of Horizontal Transfer (IHTs) (Tettelin

Differences in the presence of specific genes

Prior to the availability of complete genome sequences, a significant amount was already known about some gene differences between the Neisseria species and strains. Because of the predominant focus of research upon disease, these studies largely focused upon virulence determinants.

Degenerate genes

A noticeable feature of all the completed neisserial genome sequences is the presence of numerous genes that contain frame-shifts, deletions, and mutations affecting coding potential, as well as some instances of insertional inactivation.

porB

There are several known variations of the porB gene, encoding a porin capable of translocating into host cell mitochondrial membranes that has been found to both cause (Müller et al., 2000, Müller et al., 1999) and prevent apoptosis of host cells (Massari et al., 2000, Massari et al., 2003). These opposing observations may be due to differences in the host cells, bacterial strains, protein purification methods, growth media, stages of infection, and/or variations in the porB sequence (Binnicker

opa

The pathogenic Neisseria spp. have multiple copies of the opa gene; three or four copies in N. meningitidis, which encode what were originally called the class 5 proteins, and up to 11 copies in N. gonorrhoeae, which encode what were called the P.II proteins. These proteins are abundant outer membrane proteins that target certain host cell CEA family receptors and syndecan proteoglycan family receptors (Chen et al., 1997, Chen et al., 1995, Popp et al., 1999, van Putten and Paul, 1995, Virji et

Phase variation

Phase variation describes a process of gene ON/OFF switching that is associated with genes that are adaptive for different environmental conditions. In the Neisseria spp. gene switching is associated with simple sequence repeats that can be used to identify genes with phase variable potential. Further, a greater proportion of these genes differ between the sequenced strains than do other genes. There are also variations in whether the genes, when present, are phase variable. There are therefore

Presence and location of mobile non-coding elements

In addition to differences in coding sequences between strains, several non-coding elements are variably present or are present in different locations between different strains.

One of the most clearly described IS elements in N. meningitidis is IS1301, which has been found in 29% of meningococci tested, and is present in all serogroups. It has not been found in other Neisseria spp. (Hilse et al., 2000). Disruptions of siaA and porA by IS1301 have been reported in meningococci (Hammerschmidt et

Presence of extra-chromosomal elements

In terms of the variety of plasmids found within each pathogenic Neisseria species, and the carriage frequency, little has changed in the 15 years since this topic was last reviewed (Dillon and Yeung, 1989, Roberts, 1989). Most isolates of N. gonorrhoeae, but not N. meningitidis, carry plasmids. Most, but not all, of these plasmids are specific to one or other of the species. While the potential impact of plasmid carriage may have changed little in those 15 years, our understanding of the

Conclusions

Above all, the key messages from this review are ones of change and flexibility. These species were known to have relatively panmictic population structures (Smith et al., 1993) due to frequent intra-species recombination events facilitated by a common uptake signal sequence (Elkins et al., 1991, Goodman and Scocca, 1988). In addition, these species have been recognized to generate diversity through a silent cassette system for the generation of pilin variants (Swanson et al., 1987), and many

Acknowledgments

LAS is supported by a Wellcome Trust Project Grant. The authors would like to thank Dr Simon McGowan, of the Dunn School/WIMM Computational Biology Research Group, for the whole genome comparisons presented in Fig. 1, and Dr Charlene Kahler for a comparison of regulatory genes found in the sequenced genomes. Work in the Davies laboratory was supported by the Australian Bacterial Pathogenesis Program, funded by a Program Grant from the Australian National Health and Medical Research Council.

The

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