Neisseria genomics: current status and future perspectives

Abstract High-throughput whole genome sequencing has unlocked a multitude of possibilities enabling members of the Neisseria genus to be examined with unprecedented detail, including the human pathogens Neisseria meningitidis and Neisseria gonorrhoeae. To maximise the potential benefit of this for public health, it is becoming increasingly important to ensure that this plethora of data are adequately stored, disseminated and made readily accessible. Investigations facilitating cross-species comparisons as well as the analysis of global datasets will allow differences among and within species and across geographic locations and different times to be identified, improving our understanding of the distinct phenotypes observed. Recent advances in high-throughput platforms that measure the transcriptome, proteome and/or epigenome are also becoming increasingly employed to explore the complexities of Neisseria biology. An integrated approach to the analysis of these is essential to fully understand the impact these may have in the Neisseria genus. This article reviews the current status of some of the tools available for next generation sequence analysis at the dawn of the ‘post-genomic’ era.

[1]  Kristin Reiche,et al.  The primary transcriptome of the major human pathogen Helicobacter pylori , 2010, Nature.

[2]  Jane W. Marsh,et al.  Genomic Investigation Reveals Highly Conserved, Mosaic, Recombination Events Associated with Capsular Switching among Invasive Neisseria meningitidis Serogroup W Sequence Type (ST)-11 Strains , 2016, Genome biology and evolution.

[3]  W. Shafer,et al.  The MtrR repressor binds the DNA sequence between the mtrR and mtrC genes of Neisseria gonorrhoeae , 1997, Journal of bacteriology.

[4]  B. Tjaden,et al.  The Gonococcal Transcriptome during Infection of the Lower Genital Tract in Women , 2015, PloS one.

[5]  Carmen Buchrieser,et al.  NeMeSys: a biological resource for narrowing the gap between sequence and function in the human pathogen Neisseria meningitidis , 2009, Genome Biology.

[6]  Richard Durbin,et al.  Sequence analysis Fast and accurate short read alignment with Burrows – Wheeler transform , 2009 .

[7]  Andrew J. Page,et al.  Roary: rapid large-scale prokaryote pan genome analysis , 2015, bioRxiv.

[8]  J. Weber,et al.  Human whole-genome shotgun sequencing. , 1997, Genome research.

[9]  Time-resolved dual RNA-Seq reveals extensive rewiring of lung epithelial and pneumococcal transcriptomes during early infection , 2016 .

[10]  C. del Rio,et al.  Population structure of Neisseria gonorrhoeae based on whole genome data and its relationship with antibiotic resistance , 2015, PeerJ.

[11]  W. Shafer,et al.  Transcriptional control of the mtr efflux system of Neisseria gonorrhoeae , 1995, Journal of bacteriology.

[12]  Brian D. Ondov,et al.  Mash: fast genome and metagenome distance estimation using MinHash , 2015, Genome Biology.

[13]  J. Parkhill,et al.  A genomic approach to bacterial taxonomy: an examination and proposed reclassification of species within the genus Neisseria , 2012, Microbiology.

[14]  M. Bochud,et al.  A functional microsatellite of the macrophage migration inhibitory factor gene associated with meningococcal disease , 2012, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[15]  Martin C. J. Maiden,et al.  BIGSdb: Scalable analysis of bacterial genome variation at the population level , 2010, BMC Bioinformatics.

[16]  Zhaohui S. Qin,et al.  The single-species metagenome: subtyping Staphylococcus aureus core genome sequences from shotgun metagenomic data , 2015, bioRxiv.

[17]  S. Ladhani,et al.  Added value of PCR-testing for confirmation of invasive meningococcal disease in England. , 2013, The Journal of infection.

[18]  S. Bentley,et al.  Genotypic and Phenotypic Modifications of Neisseria meningitidis after an Accidental Human Passage , 2011, PloS one.

[19]  J. Bray,et al.  MLST revisited: the gene-by-gene approach to bacterial genomics , 2013, Nature Reviews Microbiology.

[20]  Jenny Wachter,et al.  Small transcriptome analysis indicates that the enzyme RppH influences both the quality and quantity of sRNAs in Neisseria gonorrhoeae. , 2015, FEMS microbiology letters.

[21]  Johannes Tramper,et al.  Modeling Neisseria meningitidis metabolism: from genome to metabolic fluxes , 2007, Genome Biology.

[22]  S. Harris,et al.  WGS analysis and molecular resistance mechanisms of azithromycin-resistant (MIC >2 mg/L) Neisseria gonorrhoeae isolates in Europe from 2009 to 2014. , 2016, The Journal of antimicrobial chemotherapy.

[23]  J. Vogel,et al.  Accelerating Discovery and Functional Analysis of Small RNAs with New Technologies. , 2015, Annual review of genetics.

[24]  Teresa M. Bergholz,et al.  Determination of Evolutionary Relationships of Outbreak-Associated Listeria monocytogenes Strains of Serotypes 1/2a and 1/2b by Whole-Genome Sequencing , 2015, Applied and Environmental Microbiology.

[25]  R. Rappuoli,et al.  Distribution and genetic variability of three vaccine components in a panel of strains representative of the diversity of serogroup B meningococcus. , 2009, Vaccine.

[26]  D. Low,et al.  Extensive Genomic Variation within Clonal Complexes of Neisseria meningitidis , 2011, Genome biology and evolution.

[27]  R. Schwarz,et al.  Comparative Genome Biology of a Serogroup B Carriage and Disease Strain Supports a Polygenic Nature of Meningococcal Virulence , 2010, Journal of bacteriology.

[28]  Laty A. Cahoon,et al.  Transcription of a cis-acting, Noncoding, Small RNA Is Required for Pilin Antigenic Variation in Neisseria gonorrhoeae , 2013, PLoS pathogens.

[29]  B. Barrell,et al.  Complete DNA sequence of a serogroup A strain of Neisseria meningitidis Z2491 , 2000, Nature.

[30]  T. Dandekar,et al.  Transcriptomic buffering of cryptic genetic variation contributes to meningococcal virulence , 2017, BMC Genomics.

[31]  Joanne R. Winter,et al.  Interpreting whole genome sequencing for investigating tuberculosis transmission: a systematic review , 2016, BMC Medicine.

[32]  M. Maiden,et al.  Identifying Neisseria Species by Use of the 50S Ribosomal Protein L6 (rplF) Gene , 2014, Journal of Clinical Microbiology.

[33]  K. Jolley,et al.  Genome sequence analyses show that Neisseria oralis is the same species as ‘Neisseria mucosa var. heidelbergensis’ , 2013, International journal of systematic and evolutionary microbiology.

[34]  D. Harmsen,et al.  Evolutionary Events Associated with an Outbreak of Meningococcal Disease in Men Who Have Sex with Men , 2016, PloS one.

[35]  Ahmad A Mannan,et al.  Interrogation of global mutagenesis data with a genome scale model of Neisseria meningitidis to assess gene fitness in vitro and in sera , 2011, Genome Biology.

[36]  J. Parkhill,et al.  Pneumococcal Capsular Switching: A Historical Perspective , 2012, The Journal of infectious diseases.

[37]  Daniel R Zerbino,et al.  Using the Velvet de novo Assembler for Short‐Read Sequencing Technologies , 2010, Current protocols in bioinformatics.

[38]  J. Bray,et al.  Genomic Analysis of the Evolution and Global Spread of Hyper-invasive Meningococcal Lineage 5 , 2015, EBioMedicine.

[39]  Hélène Omer,et al.  Characterization of MDAΦ, a temperate filamentous bacteriophage of Neisseria meningitidis. , 2016, Microbiology.

[40]  M. Unemo,et al.  A Novel Mechanism of High-Level, Broad-Spectrum Antibiotic Resistance Caused by a Single Base Pair Change in Neisseria gonorrhoeae , 2011, mBio.

[41]  Tyson A. Clark,et al.  griffith . edu . au Specificity of the ModA 11 , ModA 12 and ModD 1 epigenetic regulator N 6-adenine DNA methyltransferases of Neisseria meningitidis , 2017 .

[42]  M. Maiden,et al.  Genomic analysis of urogenital and rectal Neisseria meningitidis isolates reveals encapsulated hyperinvasive meningococci and coincident multidrug-resistant gonococci , 2017, Sexually Transmitted Infections.

[43]  S. Salzberg,et al.  Complete genome sequence of Neisseria meningitidis serogroup B strain MC58. , 2000, Science.

[44]  M. Maiden,et al.  Meningococcal vaccine antigen diversity in global databases. , 2015, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[45]  C. Thermes,et al.  Ten years of next-generation sequencing technology. , 2014, Trends in genetics : TIG.

[46]  A. Anselmo,et al.  Genome-based study of a spatio-temporal cluster of invasive meningococcal disease due to Neisseria meningitidis serogroup C, clonal complex 11. , 2016, The Journal of infection.

[47]  C. Khor,et al.  Genome-wide association study identifies variants in the CFH region associated with host susceptibility to meningococcal disease , 2010, Nature Genetics.

[48]  C. Donati,et al.  Serotype IV Streptococcus agalactiae ST-452 has arisen from large genomic recombination events between CC23 and the hypervirulent CC17 lineages , 2016, Scientific Reports.

[49]  Daniel J. Wilson,et al.  Whole-genome sequencing to determine transmission of Neisseria gonorrhoeae: an observational study. , 2016, The Lancet. Infectious diseases.

[50]  K. Jolley,et al.  Automated extraction of typing information for bacterial pathogens from whole genome sequence data: Neisseria meningitidis as an exemplar. , 2013, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[51]  R. Fleischmann,et al.  Whole-genome random sequencing and assembly of Haemophilus influenzae Rd. , 1995, Science.

[52]  F. Sanger,et al.  DNA sequencing with chain-terminating inhibitors. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[53]  R. Mcclure,et al.  Role of Hfq in iron-dependent and -independent gene regulation in Neisseria meningitidis , 2010, Microbiology.

[54]  Jörg Vogel,et al.  Processing-independent CRISPR RNAs limit natural transformation in Neisseria meningitidis. , 2013, Molecular cell.

[55]  B. Spratt Exploring the concept of clonality in bacteria. , 2004, Methods in molecular biology.

[56]  Georgios S. Vernikos,et al.  Independent evolution of the core and accessory gene sets in the genus Neisseria: insights gained from the genome of Neisseria lactamica isolate 020-06 , 2010, BMC Genomics.

[57]  Tyson A. Clark,et al.  Specificity of the ModA11, ModA12 and ModD1 epigenetic regulator N6-adenine DNA methyltransferases of Neisseria meningitidis , 2015, Nucleic acids research.

[58]  W. Gilbert,et al.  Sequencing end-labeled DNA with base-specific chemical cleavages. , 1980, Methods in enzymology.

[59]  D. Serruto,et al.  Analysis of the Regulated Transcriptome of Neisseria meningitidis in Human Blood Using a Tiling Array , 2012, Journal of bacteriology.

[60]  J. Vogel,et al.  The primary transcriptome of Neisseria meningitidis and its interaction with the RNA chaperone Hfq , 2017, Nucleic acids research.

[61]  Teresa A. Batteiger,et al.  Neisseria meningitidis ST11 Complex Isolates Associated with Nongonococcal Urethritis, Indiana, USA, 2015–2016 , 2017, Emerging infectious diseases.

[62]  Brian D. Ondov,et al.  The Harvest suite for rapid core-genome alignment and visualization of thousands of intraspecific microbial genomes , 2014, Genome Biology.

[63]  R. Rappuoli,et al.  Prevalence and genetic diversity of candidate vaccine antigens among invasive Neisseria meningitidis isolates in the United States. , 2011, Vaccine.

[64]  Konrad U. Förstner,et al.  Grad-seq guides the discovery of ProQ as a major small RNA-binding protein , 2016, Proceedings of the National Academy of Sciences.

[65]  J. Badge DNA sequencing. , 1998, Methods in molecular biology.

[66]  Pascale Cossart,et al.  Term-seq reveals abundant ribo-regulation of antibiotics resistance in bacteria , 2016, Science.

[67]  P. O’Toole,et al.  Next-generation sequencing technologies and their impact on microbial genomics. , 2013, Briefings in functional genomics.

[68]  Silvia Bottini,et al.  Global Transcriptome Analysis Reveals Small RNAs Affecting Neisseria meningitidis Bacteremia , 2015, PloS one.

[69]  A. van der Ende,et al.  Neisseria meningitidis Uses Sibling Small Regulatory RNAs To Switch from Cataplerotic to Anaplerotic Metabolism , 2017, mBio.

[70]  M. Ragan,et al.  Is Multiple-Sequence Alignment Required for Accurate Inference of Phylogeny? , 2007, Systematic biology.

[71]  R. Fleischmann,et al.  The Minimal Gene Complement of Mycoplasma genitalium , 1995, Science.

[72]  M. Gorla,et al.  Genomic resolution of an aggressive, widespread, diverse and expanding meningococcal serogroup B, C and W lineage , 2015, The Journal of infection.

[73]  Nicole Wolter,et al.  Clinical Validation of Multiplex Real-Time PCR Assays for Detection of Bacterial Meningitis Pathogens , 2011, Journal of Clinical Microbiology.

[74]  Torsten Seemann,et al.  Prokka: rapid prokaryotic genome annotation , 2014, Bioinform..

[75]  R. Exley,et al.  Characterization of a Novel Antisense RNA in the Major Pilin Locus of Neisseria meningitidis Influencing Antigenic Variation , 2015, Journal of bacteriology.

[76]  Johannes Elias,et al.  Metabolism and virulence in Neisseria meningitidis , 2014, Front. Cell. Infect. Microbiol..

[77]  Jonathan R. Karr,et al.  A Whole-Cell Computational Model Predicts Phenotype from Genotype , 2012, Cell.

[78]  J. Bray,et al.  Resolution of a Protracted Serogroup B Meningococcal Outbreak with Whole-Genome Sequencing Shows Interspecies Genetic Transfer , 2016, Journal of Clinical Microbiology.

[79]  A. Goesmann,et al.  Comparative Genome Sequencing Reveals Within-Host Genetic Changes in Neisseria meningitidis during Invasive Disease , 2017, PloS one.

[80]  E. Moxon,et al.  Distribution of Bexsero® Antigen Sequence Types (BASTs) in invasive meningococcal disease isolates: Implications for immunisation , 2016, Vaccine.

[81]  D. Trees,et al.  Genomic sequencing of Neisseria gonorrhoeae to respond to the urgent threat of antimicrobial-resistant gonorrhea , 2017, Pathogens and disease.

[82]  Keith A. Jolley,et al.  Ribosomal multilocus sequence typing: universal characterization of bacteria from domain to strain , 2012, Microbiology.

[83]  C. Ison,et al.  Detection of mixed infection of Neisseria gonorrhoeae , 2003, Sexually transmitted infections.

[84]  J. Vogel,et al.  Deep Sequencing Analysis of Small Noncoding RNA and mRNA Targets of the Global Post-Transcriptional Regulator, Hfq , 2008, PLoS genetics.

[85]  Stephen D. Bentley,et al.  Large scale genomic analysis shows no evidence for pathogen adaptation between the blood and cerebrospinal fluid niches during bacterial meningitis , 2017, Microbial genomics.

[86]  Xin Wang,et al.  sodC-Based Real-Time PCR for Detection of Neisseria meningitidis , 2011, PloS one.

[87]  Xin Wang,et al.  Genomic Epidemiology of Hypervirulent Serogroup W, ST-11 Neisseria meningitidis , 2015, EBioMedicine.

[88]  Kelvin H. Lee,et al.  Genomic analysis. , 2000, Current opinion in biotechnology.

[89]  Julian Parkhill,et al.  Genomic epidemiology of Neisseria gonorrhoeae with reduced susceptibility to cefixime in the USA: a retrospective observational study , 2014, The Lancet. Infectious diseases.

[90]  Konrad U. Förstner,et al.  Dual RNA-seq unveils noncoding RNA functions in host–pathogen interactions , 2016, Nature.

[91]  Ilias Tagkopoulos,et al.  An integrative, multi-scale, genome-wide model reveals the phenotypic landscape of Escherichia coli , 2014, Molecular systems biology.

[92]  Stephen D. Bentley,et al.  Genomic Analysis and Comparison of Two Gonorrhea Outbreaks , 2016, mBio.

[93]  Gonçalo R. Abecasis,et al.  The Sequence Alignment/Map format and SAMtools , 2009, Bioinform..

[94]  Tom Slezak,et al.  kSNP3.0: SNP detection and phylogenetic analysis of genomes without genome alignment or reference genome , 2015, Bioinform..

[95]  Yonatan H. Grad,et al.  WGS to predict antibiotic MICs for Neisseria gonorrhoeae , 2017, The Journal of antimicrobial chemotherapy.

[96]  Y. Grad,et al.  Genomic analyses of Neisseria gonorrhoeae reveal an association of the gonococcal genetic island with antimicrobial resistance , 2016, The Journal of infection.

[97]  Rolf Backofen,et al.  Global RNA recognition patterns of post‐transcriptional regulators Hfq and CsrA revealed by UV crosslinking in vivo , 2016, The EMBO journal.

[98]  Jacqueline A. Keane,et al.  Rapid phylogenetic analysis of large samples of recombinant bacterial whole genome sequences using Gubbins , 2014, Nucleic acids research.

[99]  F. Baas,et al.  Deep Sequencing Whole Transcriptome Exploration of the σE Regulon in Neisseria meningitidis , 2011, PloS one.

[100]  Anne Jamet,et al.  A New Family of Secreted Toxins in Pathogenic Neisseria Species , 2015, PLoS pathogens.

[101]  Chinelo Obi,et al.  Frequency and correlates of culture-positive infection with Neisseria gonorrhoeae in England: a review of sentinel surveillance data , 2014, Sexually Transmitted Infections.

[102]  Mario Recker,et al.  Role of selection in the emergence of lineages and the evolution of virulence in Neisseria meningitidis , 2008, Proceedings of the National Academy of Sciences.

[103]  R. Rosselló-Móra,et al.  Shifting the genomic gold standard for the prokaryotic species definition , 2009, Proceedings of the National Academy of Sciences.

[104]  Joshua A. Lerman,et al.  Genome-scale metabolic reconstructions of multiple Escherichia coli strains highlight strain-specific adaptations to nutritional environments , 2013, Proceedings of the National Academy of Sciences.

[105]  J. Roach,et al.  Pairwise end sequencing: a unified approach to genomic mapping and sequencing. , 1995, Genomics.

[106]  Sergey I. Nikolenko,et al.  SPAdes: A New Genome Assembly Algorithm and Its Applications to Single-Cell Sequencing , 2012, J. Comput. Biol..

[107]  Aldert L. Zomer,et al.  Comprehensive Identification of Meningococcal Genes and Small Noncoding RNAs Required for Host Cell Colonization , 2016, mBio.

[108]  R. Rappuoli,et al.  A universal vaccine for serogroup B meningococcus. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[109]  崔玉军,et al.  genomic epidemiology , 2012 .

[110]  Rick L. Stevens,et al.  The RAST Server: Rapid Annotations using Subsystems Technology , 2008, BMC Genomics.

[111]  Julian Parkhill,et al.  A gene-by-gene population genomics platform: de novo assembly, annotation and genealogical analysis of 108 representative Neisseria meningitidis genomes , 2014, BMC Genomics.

[112]  Ryan T Novak,et al.  The Establishment and Diversification of Epidemic-Associated Serogroup W Meningococcus in the African Meningitis Belt, 1994 to 2012 , 2016, mSphere.

[113]  M. Maiden,et al.  Population and Functional Genomics of Neisseria Revealed with Gene-by-Gene Approaches , 2016, Journal of Clinical Microbiology.