scholarly journals Genomic Characterization of Urethritis-Associated Neisseria meningitidis Shows that a Wide Range of N. meningitidis Strains Can Cause Urethritis

2017 ◽  
Vol 55 (12) ◽  
pp. 3374-3383 ◽  
Author(s):  
Kevin C. Ma ◽  
Magnus Unemo ◽  
Samo Jeverica ◽  
Robert D. Kirkcaldy ◽  
Hideyuki Takahashi ◽  
...  
Keyword(s):  
Neisseria Meningitidis ◽  
Etiologic Agent ◽  
Factor H ◽  
Urogenital Tract ◽  
Genetic Characteristics ◽  
Content Type ◽  
Nitrite Reductase Gene ◽  
Reductase Gene ◽  
Wide Range ◽  
Genomic Characterization

ABSTRACTNeisseria meningitidis, typically a resident of the oro- or nasopharynx and the causative agent of meningococcal meningitis and meningococcemia, is capable of invading and colonizing the urogenital tract. This can result in urethritis, akin to the syndrome caused by its sister species,N. gonorrhoeae, the etiologic agent of gonorrhea. Recently, meningococcal strains associated with outbreaks of urethritis were reported to share genetic characteristics with the gonococcus, raising the question of the extent to which these strains contain features that promote adaptation to the genitourinary niche, making them gonococcus-like and distinguishing them from otherN. meningitidisstrains. Here, we analyzed the genomes of 39 diverseN. meningitidisisolates associated with urethritis, collected independently over a decade and across three continents. In particular, we characterized the diversity of the nitrite reductase gene (aniA), the factor H-binding protein gene (fHbp), and the capsule biosynthetic locus, all of which are loci previously suggested to be associated with urogenital colonization. We observed notable diversity, including frameshift variants, inaniAandfHbpand the presence of intact, disrupted, and absent capsule biosynthetic genes, indicating that urogenital colonization and urethritis caused byN. meningitidisare possible across a range of meningococcal genotypes. Previously identified allelic patterns in urethritis-associatedN. meningitidisstrains may reflect genetic diversity in the underlying meningococcal population rather than novel adaptation to the urogenital tract.

Microaerobic denitrification in Neisseria meningitidis

2005 ◽  
Vol 33 (1) ◽  
pp. 134-136 ◽  
Author(s):  
J.D. Rock ◽  
J.W.B. Moir
Keyword(s):  
Neisseria Meningitidis ◽  
Respiratory Chain ◽  
Growth Conditions ◽  
Nitric Oxide Reductase ◽  
Genome Sequences ◽  
Course Of Disease ◽  
Nitrite Reductase Gene ◽  
Reductase Gene ◽  
Microaerobic Conditions ◽  
Limited Oxygen

The major aetiological agent of human bacterial meningitis is Neisseria meningitidis. During the course of disease and host colonization, the bacterium has to withstand limited oxygen availability. Nitrogen oxide and nitrogen oxyanions are thought to be present, which may constitute an alternative sink for electrons from the N. meningitidis respiratory chain. A partial denitrification pathway is encoded by the aniA nitrite reductase gene and the norB nitric oxide reductase gene. Analysis of the completed genome sequences of two N. meningitidis strains is used to generate a model for the membrane-associated respiratory chain of this organism. Analysis of aniA expression indicates it to be controlled primarily by oxygen and secondarily by nitrite. The ability of N. meningitidis to denitrify relies on microaerobic growth conditions. Here we show that under microaerobic conditions nitrite supplements oxygen as an alternative respiratory substrate.

scholarly journals Potentially Mobile Denitrification Genes Identified inAzospirillumsp. Strain TSH58

2018 ◽  
Vol 85 (2) ◽  
Author(s):  
Jeonghwan Jang ◽  
Yoriko Sakai ◽  
Keishi Senoo ◽  
Satoshi Ishii
Keyword(s):  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Nitrite Reductase ◽  
Rrna Gene ◽  
Content Type ◽  
Denitrification Gene ◽  
Nitrite Reductase Gene ◽  
Reductase Gene ◽  
Denitrification Genes ◽  
The 16S Rrna Gene

ABSTRACTDenitrification ability is sporadically distributed among diverse bacteria, archaea, and fungi. In addition, disagreement has been found between denitrification gene phylogenies and the 16S rRNA gene phylogeny. These facts have suggested potential occurrences of horizontal gene transfer (HGT) for the denitrification genes. However, evidence of HGT has not been clearly presented thus far. In this study, we identified the sequences and the localization of the nitrite reductase genes in the genomes of 41 denitrifyingAzospirillumsp. strains and searched for mobile genetic elements that contain denitrification genes. AllAzospirillumsp. strains examined in this study possessed multiple replicons (4 to 11 replicons), with their sizes ranging from 7 to 1,031 kbp. Among those, the nitrite reductase genenirKwas located on large replicons (549 to 941 kbp). Genome sequencing showed thatAzospirillumstrains that had similarnirKsequences also shared similarnir-norgene arrangements, especially between the TSH58, Sp7T, and Sp245 strains. In addition to the high similarity betweennir-norgene clusters among the threeAzospirillumstrains, a composite transposon structure was identified in the genome of strain TSH58, which contains thenir-norgene cluster and the novel IS6family insertion sequences (ISAz581and ISAz582). ThenirKgene within the composite transposon system was actively transcribed under denitrification-inducing conditions. Although not experimentally verified in this study, the composite transposon system containing thenir-norgene cluster could be transferred to other cells if it is moved to a prophage region and the phage becomes activated and released outside the cells. Taken together, strain TSH58 most likely acquired its denitrification ability by HGT from closely relatedAzospirillumsp. denitrifiers.IMPORTANCEThe evolutionary history of denitrification is complex. While the occurrence of horizontal gene transfer has been suggested for denitrification genes, most studies report circumstantial evidences, such as disagreement between denitrification gene phylogenies and the 16S rRNA gene phylogeny. Based on the comparative genome analyses ofAzospirillumsp. denitrifiers, we identified denitrification genes, includingnirKandnorCBQD, located on a mobile genetic element in the genome ofAzospirillumsp. strain TSH58. ThenirKwas actively transcribed under denitrification-inducing conditions. Since this gene was the sole nitrite reductase gene in strain TSH58, this strain most likely benefitted by acquiring denitrification genes via horizontal gene transfer. This finding will significantly advance our scientific knowledge regarding the ecology and evolution of denitrification.

scholarly journals Characterization of Neisseria meningitidis Isolates That Do Not Express the Virulence Factor and Vaccine Antigen Factor H Binding Protein

2011 ◽  
Vol 18 (6) ◽  
pp. 1002-1014 ◽  
Author(s):  
Jay Lucidarme ◽  
Lionel Tan ◽  
Rachel M. Exley ◽  
Jamie Findlow ◽  
Ray Borrow ◽  
...  
Keyword(s):  
Neisseria Meningitidis ◽  
Binding Protein ◽  
Factor H ◽  
Negative Regulator ◽  
Vaccine Antigen ◽  
Natural Immunity ◽  
Content Type ◽  
Reading Frame ◽  
Flanking Sequences

ABSTRACTNeisseria meningitidisremains a leading cause of bacterial sepsis and meningitis. Complement is a key component of natural immunity against this important human pathogen, which has evolved multiple mechanisms to evade complement-mediated lysis. One approach adopted by the meningococcus is to recruit a human negative regulator of the complement system, factor H (fH), to its surface via a lipoprotein, factor H binding protein (fHbp). Additionally, fHbp is a key antigen in vaccines currently being evaluated in clinical trials. Here we characterize strains ofN. meningitidisfrom several distinct clonal complexes which do not express fHbp; all strains were recovered from patients with disseminated meningococcal disease. We demonstrate that these strains have either a frameshift mutation in thefHbpopen reading frame or have entirely lostfHbpand some flanking sequences. No fH binding was detected to other ligands among thefHbp-negative strains. The implications of these findings for meningococcal pathogenesis and prevention are discussed.

scholarly journals A Longitudinal Epidemiology Study of Meningococcal Carriage in Students 13 to 25 Years Old in Quebec

mSphere ◽  
2018 ◽  
Vol 3 (6) ◽  
Author(s):  
Rodica Gilca ◽  
Philippe De Wals ◽  
Sheila M. Nolan ◽  
Nicholas Kitchin ◽  
Joseph J. Eiden ◽  
...  
Keyword(s):  
University Students ◽  
Neisseria Meningitidis ◽  
Age Groups ◽  
Ninth Grade ◽  
Factor H ◽  
Detection Methods ◽  
Quebec City ◽  
Content Type ◽  
College Entry ◽  
Ninth Grade Students

ABSTRACTNeisseria meningitidiscarriage data are necessary to inform serogroup B (NmB) immunization program implementation. This longitudinal study compared detection methods to measureN. meningitidisthroat carriage prevalence in Quebec from November 2010 to December 2013 using cultured swab isolates and direct swab PCR from students in ninth grade (aged 13 to 15 years;n= 534) and eleventh grade/college entry (16 to 18 years;n= 363) and in university students in dormitories (18 to 25 years;n= 360) at 3 time points per group. Meningococcal and NmB carriage rates were lower in ninth- and eleventh-grade/college entry students than university students, regardless of methodology. Genotyping cultured isolates by PCR detected NmB and non-NmB in 2.1% and 7.3% of ninth-grade students, in 1.7% and 7.2% of eleventh-grade/college entry students, and in 7.5% and 21.9% of university students, respectively. NmB acquisition rates were 1.9, 0.7, and 3.3 per 1,000 person-months across respective age groups. Most NmB isolates (94.7%, 76.9%, and 86.8%, respectively) expressed subfamily A factor H binding-protein (fHBP) variants. The most common non-NmB serogroups were NmY (1.7%/1.1%) from ninth grade and eleventh grade/college entry and NmW (2.8%) from university students. Genomic analyses detected disease-associated sequence types in carriage isolates, and carriage could persist for months. This is the largest longitudinal carriage study in Canada and the first to report fHBP variants in NmB carriage isolates in healthy Canadians. These data contribute to identification of the optimal window for NmB vaccination in precollege adolescents and provide a baseline for investigating NmB vaccination effects on carriage in this population.IMPORTANCEDisease caused byNeisseria meningitidisis associated with serious complications and a high fatality rate. Asymptomatic individuals can harbor the bacterium in the throat, a state known as “carriage,” which can lead to person-to-person spread of the pathogen. This study examinedN. meningitidiscarriage from 2010 to 2013 among 2 groups in the Quebec City region: ninth-grade students (aged 13 to 15 years), who were also followed in their last year of high school (eleventh grade/college entry; 16 to 18 years), and university students (18 to 25 years); both groups have been shown in some other geographic regions to have high rates of carriage. This study demonstrated thatN. meningitidiscarriage rates were higher among university students in dormitories than ninth-grade and eleventh-grade/college entry students. Understanding carriage rates in these age groups leads to better strategies to controlN. meningitidisby targeting vaccination to those responsible for transmission within the population.

scholarly journals Identification of Hypoxia-Inducible Target Genes of Aspergillus fumigatus by Transcriptome Analysis Reveals Cellular Respiration as an Important Contributor to Hypoxic Survival

2014 ◽  
Vol 13 (9) ◽  
pp. 1241-1253 ◽  
Author(s):  
Kristin Kroll ◽  
Vera Pähtz ◽  
Falk Hillmann ◽  
Yakir Vaknin ◽  
Wolfgang Schmidt-Heck ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Nitrogen Metabolism ◽  
Transcriptome Analysis ◽  
Metal Ion ◽  
Target Genes ◽  
Cellular Respiration ◽  
Cell Wall Polysaccharide ◽  
Content Type ◽  
Nitrite Reductase Gene ◽  
Reductase Gene

ABSTRACT Aspergillus fumigatus is an opportunistic, airborne pathogen that causes invasive aspergillosis in immunocompromised patients. During the infection process, A. fumigatus is challenged by hypoxic microenvironments occurring in inflammatory, necrotic tissue. To gain further insights into the adaptation mechanism, A. fumigatus was cultivated in an oxygen-controlled chemostat under hypoxic and normoxic conditions. Transcriptome analysis revealed a significant increase in transcripts associated with cell wall polysaccharide metabolism, amino acid and metal ion transport, nitrogen metabolism, and glycolysis. A concomitant reduction in transcript levels was observed with cellular trafficking and G-protein-coupled signaling. To learn more about the functional roles of hypoxia-induced transcripts, we deleted A. fumigatus genes putatively involved in reactive nitrogen species detoxification ( fhpA ), NAD + regeneration ( frdA and osmA ), nitrogen metabolism ( niaD and niiA ), and respiration ( rcfB ). We show that the nitric oxygen (NO)-detoxifying flavohemoprotein gene fhpA is strongly induced by hypoxia independent of the nitrogen source but is dispensable for hypoxic survival. By deleting the nitrate reductase gene niaD , the nitrite reductase gene niiA , and the two fumarate reductase genes frdA and osmA , we found that alternative electron acceptors, such as nitrate and fumarate, do not have a significant impact on growth of A. fumigatus during hypoxia, but functional mitochondrial respiratory chain complexes are essential under these conditions. Inhibition studies indicated that primarily complexes III and IV play a crucial role in the hypoxic growth of A. fumigatus .

scholarly journals A Novel Angular Dioxygenase Gene Cluster Encoding 3-Phenoxybenzoate 1′,2′-Dioxygenase in Sphingobium wenxiniae JZ-1

2014 ◽  
Vol 80 (13) ◽  
pp. 3811-3818 ◽  
Author(s):  
Chenghong Wang ◽  
Qing Chen ◽  
Rui Wang ◽  
Chao Shi ◽  
Xin Yan ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Heme Iron ◽  
Transcriptional Level ◽  
Content Type ◽  
Type Iv ◽  
Reductase Gene ◽  
Wide Range ◽  
Dioxygenase Gene ◽  
Sphingomonas Wittichii ◽  
Angular Dioxygenase

ABSTRACTSphingobium wenxiniaeJZ-1 utilizes a wide range of pyrethroids and their metabolic product, 3-phenoxybenzoate, as sources of carbon and energy. A mutant JZ-1 strain, MJZ-1, defective in the degradation of 3-phenoxybenzoate was obtained by successive streaking on LB agar. Comparison of the draft genomes of strains JZ-1 and MJZ-1 revealed that a 29,366-bp DNA fragment containing a putative angular dioxygenase gene cluster (pbaA1A2B) is missing in strain MJZ-1. PbaA1, PbaA2, and PbaB share 65%, 52%, and 10% identity with the corresponding α and β subunits and the ferredoxin component of dioxin dioxygenase fromSphingomonas wittichiiRW1, respectively. Complementation ofpbaA1A2Bin strain MJZ-1 resulted in the active 3-phenoxybenzoate 1′,2′-dioxygenase, but the enzyme activity inEscherichia coliwas achieved only through the coexpression ofpbaA1A2Band a glutathione reductase (GR)-type reductase gene,pbaC, indicating that the 3-phenoxybenzoate 1′,2′-dioxygenase belongs to a type IV Rieske non-heme iron aromatic ring-hydroxylating oxygenase system consisting of a hetero-oligomeric oxygenase, a [2Fe-2S]-type ferredoxin, and a GR-type reductase. ThepbaCgene is not located in the immediate vicinity ofpbaA1A2B. 3-Phenoxybenzoate 1′,2′-dioxygenase catalyzes the hydroxylation in the 1′ and 2′ positions of the benzene moiety of 3-phenoxybenzoate, yielding 3-hydroxybenzoate and catechol. Transcription ofpbaA1A2BandpbaCwas induced by 3-phenoxybenzoate, but the transcriptional level ofpbaCwas far less than that ofpbaA1A2B, implying the possibility that PbaC may not be the only reductase that can physiologically transfer electrons to PbaA1A2B in strain JZ-1. Some GR-type reductases from other sphingomonad strains could also transfer electrons to PbaA1A2B, suggesting that PbaA1A2B has a low specificity for reductase.

scholarly journals Factor H binding protein (fHbp)-mediated differential complement resistance of a serogroup C Neisseria meningitidis isolate from cerebrospinal fluid of a patient with invasive meningococcal disease

2021 ◽  
Vol 3 (9) ◽  
Author(s):  
Alessandra Facchetti ◽  
Jun X. Wheeler ◽  
Caroline Vipond ◽  
Gail Whiting ◽  
Hayley Lavender ◽  
...  
Keyword(s):  
Neisseria Meningitidis ◽  
Meningococcal Disease ◽  
Close Contact ◽  
Binding Protein ◽  
Integral Membrane Protein ◽  
Factor H ◽  
Invasive Meningococcal Disease ◽  
Content Type ◽  
Type Iv ◽  
Complement Resistance

During an outbreak of invasive meningococcal disease (IMD) at the University of Southampton, UK, in 1997, two Neisseria meningitidis serogroup C isolates were retrieved from a student (‘Case’), who died of IMD, and a close contact (‘Carrier’) who, after mouth-to-mouth resuscitation on the deceased, did not contract the disease. Genomic comparison of the isolates demonstrated extensive nucleotide sequence identity, with differences identified in eight genes. Here, comparative proteomics was used to measure differential protein expression between the isolates and investigate whether the differences contributed to the clinical outcomes. A total of six proteins were differentially expressed: four proteins (methylcitrate synthase, PrpC; hypothetical integral membrane protein, Imp; fructose-1,6-bisphosphate aldolase, Fba; aldehyde dehydrogenase A, AldA) were upregulated in the Case isolate, while one protein (Type IV pilus-associated protein, PilC2) was downregulated. Peptides for factor H binding protein (fHbp), a major virulence factor and antigenic protein, were only detected in the Case, with a single base deletion (ΔT366) in the Carrier fHbp causing lack of its expression. Expression of fHbp resulted in an increased resistance of the Case isolate to complement-mediated killing in serum. Complementation of fHbp expression in the Carrier increased its serum resistance by approximately 8-fold. Moreover, a higher serum bactericidal antibody titre was seen for the Case isolate when using sera from mice immunized with Bexsero (GlaxoSmithKline), a vaccine containing fHbp as an antigenic component. This study highlights the role of fHbp in the differential complement resistance of the Case and the Carrier isolates. Expression of fHbp in the Case resulted in its increased survival in serum, possibly leading to active proliferation of the bacteria in blood and death of the student through IMD. Moreover, enhanced killing of the Case isolate by sera raised against an fHbp-containing vaccine, Bexsero, underlines the role and importance of fHbp in infection and immunity.

scholarly journals Genetic Analysis of Neisseria meningitidis Sequence Type 7 Serogroup X Originating from Serogroup A

2017 ◽  
Vol 85 (6) ◽  
Author(s):  
Bingqing Zhu ◽  
Pingping Yao ◽  
Leyi Zhang ◽  
Yuan Gao ◽  
Li Xu ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Neisseria Meningitidis ◽  
Gene Locus ◽  
Sequence Type ◽  
Specific Gene ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genetic Characteristics ◽  
Content Type ◽  
Vaccination Programs

ABSTRACT Neisseria meningitidis causes meningococcal disease, often resulting in fulminant meningitis, sepsis, and death. Vaccination programs have been developed to prevent infection of this pathogen, but serogroup replacement is a problem. Capsular switching has been an important survival mechanism for N. meningitidis, allowing the organism to evolve in the present vaccine era. However, related mechanisms have not been completely elucidated. Genetic analysis of capsular switching between diverse serogroups would help further our understanding of this pathogen. In this study, we analyzed the genetic characteristics of the sequence type 7 (ST-7) serogroup X strain that was predicted to arise from ST-7 serogroup A at the genomic level. By comparing the genomic structures and sequences, ST-7 serogroup X was closest to ST-7 serogroup A, whereas eight probable recombination regions, including the capsular gene locus, were identified. This indicated that serogroup X originated from serogroup A by recombination leading to capsular switching. The recombination involved approximately 8,540 bp from the end of the ctrC gene to the middle of the galE gene. There were more recombination regions and strain-specific single-nucleotide polymorphisms in serogroup X than in serogroup A genomes. However, no specific gene was found for each serogroup except those in the capsule gene locus.

scholarly journals Culture-Confirmed Invasive Meningococcal Disease in Canada, 2010 to 2014: Characterization of Serogroup B Neisseria meningitidis Strains and Their Predicted Coverage by the 4CMenB Vaccine

mSphere ◽  
2020 ◽  
Vol 5 (2) ◽  
Author(s):  
Raymond S. W. Tsang ◽  
Dennis K. S. Law ◽  
Rosita De Paola ◽  
Maria Giuliani ◽  
Maria Stella ◽  
...  
Keyword(s):  
Molecular Epidemiology ◽  
Neisseria Meningitidis ◽  
Meningococcal Disease ◽  
Factor H ◽  
Invasive Meningococcal Disease ◽  
Effective Control ◽  
Atlantic Region ◽  
Content Type ◽  
Laboratory Surveillance ◽  
4Cmenb Vaccine

ABSTRACT The molecular epidemiology of culture-confirmed invasive meningococcal disease (IMD) in Canada from 2010 to 2014 was studied with an emphasis on serogroup B Neisseria meningitidis (MenB) isolates, including their predicted coverage by the 4CMenB vaccine. The mean annual incidence rates of culture confirmed IMD varied from 0.19/100,000 in Ontario to 0.50/100,000 in New Brunswick and 0.59/100,000 in Quebec. In both Quebec and Atlantic region, MenB was significantly more common than other serogroups, while in other provinces, both MenB and serogroup Y (MenY) were almost equally common. The majority of MenB cases (67.0%) were in those aged ≤24 years, while most MenC (75.0%) and MenY (69.6%) cases were in adults more than 24 years old. The 349 MenB isolates were grouped into 103 sequence types (STs), 90 of which belonged to 13 clonal complexes (CCs). A large number of 4CMenB antigen genes were found among the Canadian MenB, which is predicted to encode 50 factor H binding protein (fHbp) types, 40 NHBA types, and 55 PorA genotypes. Provinces and regions were found to have their own unique MenB STs. A meningococcal antigen typing system assay predicted an overall MenB coverage by 4CMenB to be 73.6%, with higher coverage predicted for the two most common STs: 100% for ST154 and 95.9% for ST269, leading to higher coverage in both the Atlantic region and Quebec. Higher coverage (81.4%) was also found for MenB recovered from persons aged 15 to 24 years, followed by strains from infants and children ≤4 years old (75.2%) and those aged 5 to 14 years (75.0%). IMPORTANCE Laboratory surveillance of invasive meningococcal disease (IMD) is important to our understanding of the evolving nature of the Neisseria meningitidis strain types causing the disease and the potential coverage of disease strains by the newly developed vaccines. This study examined the molecular epidemiology of culture-confirmed IMD cases in Canada by examining the strain types and the potential coverage of a newly licensed 4CMenB vaccine on Canadian serogroup B N. meningitidis strains. The strain types identified in different parts of Canada appeared to be unique as well as their predicted coverage by the 4CMenB vaccine. These data were compared to data obtained from previous studies done in Canada and elsewhere globally. For effective control of IMD, laboratory surveillance of this type was found to be essential and useful to understand the dynamic nature of this disease.

scholarly journals Conservation of Meningococcal Antigens in the Genus Neisseria

mBio ◽  
2013 ◽  
Vol 4 (3) ◽  
Author(s):  
Alessandro Muzzi ◽  
Marirosa Mora ◽  
Mariagrazia Pizza ◽  
Rino Rappuoli ◽  
Claudio Donati
Keyword(s):  
Bacterial Meningitis ◽  
Respiratory Tract ◽  
Neisseria Meningitidis ◽  
Recombination Event ◽  
Factor H ◽  
High Rate ◽  
Upper Respiratory Tract ◽  
Content Type ◽  
Commensal Species ◽  
Upper Respiratory

ABSTRACTNeisseria meningitidis, one of the major causes of bacterial meningitis and sepsis, is a member of the genusNeisseria, which includes species that colonize the mucosae of many animals. Three meningococcal proteins, factor H-binding protein (fHbp), neisserial heparin-binding antigen (NHBA), andN. meningitidisadhesin A (NadA), have been described as antigens protective againstN. meningitidisof serogroup B, and they have been employed as vaccine components in preclinical and clinical studies. In the vaccine formulation, fHbp and NHBA were fused to the GNA2091 and GNA1030 proteins, respectively, to enhance protein stability and immunogenicity. To determine the possible impact of vaccination on commensal neisseriae, we determined the presence, distribution, and conservation of these antigens in the available genome sequences of the genusNeisseria, finding that fHbp, NHBA, and NadA were conserved only in species colonizing humans, while GNA1030 and GNA2091 were conserved in many human and nonhuman neisseriae. Sequence analysis showed that homologous recombination contributed to shape the evolution and distribution of both NHBA and fHbp, three major variants of which have been defined. fHbp variant 3 was probably the ancestral form of meningococcal fHbp, while fHbp variant 1 fromN. cinereawas introduced intoN. meningitidisby a recombination event. fHbp variant 2 was the result of a recombination event inserting a stretch of 483 bp from variant 1 into the variant 3 background. These data indicate that a high rate of exchange of genetic material between neisseriae that colonize the human upper respiratory tract exists.IMPORTANCEThe upper respiratory tract of healthy individuals is a complex ecosystem colonized by many bacterial species. Among these, there are representatives of the genusNeisseria, includingNeisseria meningitidis, a major cause of bacterial meningitis and sepsis. Given the close relationship between commensal and pathogenic species, a protein-based vaccine againstN. meningitidishas the potential to impact the other commensal species ofNeisseria. For this reason, we have studied the distribution and evolutionary history of the antigen components of a recombinant vaccine, 4CMenB, that recently received approval in Europe under the commercial name of Bexsero®. We found that fHbp, NHBA, and NadA can be found in some of the human commensal species and that the evolution of these antigens has been essentially shaped by the high rate of genetic exchange that occurs between strains of neisseriae that cocolonize the same environment.

Sign in / Sign up

Export Citation Format

Share Document