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Frontiers in Cellular and Infection... 2022is a gram-negative diplococcus and a transient commensal of the human nasopharynx. It shares and competes for this niche with a number of other species including and... (Review)
Review
is a gram-negative diplococcus and a transient commensal of the human nasopharynx. It shares and competes for this niche with a number of other species including and . Unlike these other members of the genus, may become invasive, crossing the epithelium of the nasopharynx and entering the bloodstream, where it rapidly proliferates causing a syndrome known as Invasive Meningococcal Disease (IMD). IMD progresses rapidly to cause septic shock and meningitis and is often fatal despite aggressive antibiotic therapy. While many of the ways in which meningococci survive in the host environment have been well studied, recent insights into the interactions between and the epithelial, serum, and endothelial environments have expanded our understanding of how IMD develops. This review seeks to incorporate recent work into the established model of pathogenesis. In particular, we focus on the competition that faces in the nasopharynx from other species, and how the genetic diversity of the meningococcus contributes to the wide range of inflammatory and pathogenic potentials observed among different lineages.
Topics: Host-Pathogen Interactions; Humans; Life Style; Meningococcal Infections; Neisseria; Neisseria meningitidis
PubMed: 35531336
DOI: 10.3389/fcimb.2022.862935 -
Frontiers in Cellular and Infection... 2022and are two obligate human pathogens that have evolved to be uniquely adapted to their host. The meningococcus is frequently carried asymptomatically in the... (Review)
Review
and are two obligate human pathogens that have evolved to be uniquely adapted to their host. The meningococcus is frequently carried asymptomatically in the nasopharynx, while gonococcal infection of the urogenital tract usually elicits a marked local inflammatory response. Other members of the genus are abundant in the upper airway where they could engage in co-operative or competitive interactions with both these pathogens. Here, we briefly outline the potential sites of contact between spp. in the body, with emphasis on the upper airway, and describe the growing yet circumstantial evidence for antagonism from carriage studies and human volunteer challenge models with . Recent laboratory studies have characterized antagonistic mechanisms that enable competition between species. Several of these mechanisms, including Multiple Adhesin family (Mafs), Two Partner Secretion Systems, and Type VI secretion system, involve direct contact between bacteria; the genetic organisation of these systems, and the domain structure of their effector molecules have striking similarities. Additionally, DNA from one species of can be toxic to another species, following uptake. More research is needed to define the full repertoire of antagonistic mechanisms in spp., their distribution in strains, their range of activity, and contribution to survival . Understanding the targets of effectors could reveal how antagonistic relationships between close relatives shape subsequent interactions between pathogens and their hosts.
Topics: Conflict of Interest; Humans; Nasopharynx; Neisseria; Neisseria gonorrhoeae; Neisseria meningitidis
PubMed: 35811666
DOI: 10.3389/fcimb.2022.913292 -
BMJ Open May 2022Infant upper respiratory microbiota are derived partly from the maternal respiratory tract, and certain microbiota are associated with altered risk of infections and...
Controlled human infection with in late pregnancy to measure horizontal transmission and microbiome changes in mother-neonate pairs: a single-arm interventional pilot study protocol.
INTRODUCTION
Infant upper respiratory microbiota are derived partly from the maternal respiratory tract, and certain microbiota are associated with altered risk of infections and respiratory disease. is a common pharyngeal commensal in young children and is associated with reduced carriage and invasive disease by . Nasal inoculation with safely and reproducibly reduces colonisation in healthy adults. We propose nasal inoculation of pregnant women with , to establish if neonatal pharyngeal colonisation occurs after birth, and to characterise microbiome evolution in mother-infant pairs over 1 month post partum.
METHODS AND ANALYSIS
20 healthy pregnant women will receive nasal inoculation with (wild type strain Y92-1009) at 36-38 weeks gestation. Upper respiratory samples, as well as optional breastmilk, umbilical cord blood and infant venous blood samples, will be collected from mother-infant pairs over 1 month post partum. We will assess safety, colonisation (by targeted PCR) and longitudinal microevolution (by whole genome sequencing), and microbiome evolution (by 16S rRNA gene sequencing).
ETHICS AND DISSEMINATION
This study has been approved by the London Central Research Ethics Committee (21/PR/0373). Findings will be published in peer-reviewed open-access journals as soon as possible.
TRIAL REGISTRATION NUMBER
NCT04784845.
Topics: Adult; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Microbiota; Mothers; Neisseria lactamica; Neisseria meningitidis; Pharynx; Pilot Projects; Pregnancy; RNA, Ribosomal, 16S
PubMed: 35584870
DOI: 10.1136/bmjopen-2021-056081 -
Microbiology (Reading, England) May 2008One potential vaccine strategy in the fight against meningococcal disease involves the exploitation of outer-membrane components of Neisseria lactamica, a commensal... (Comparative Study)
Comparative Study
One potential vaccine strategy in the fight against meningococcal disease involves the exploitation of outer-membrane components of Neisseria lactamica, a commensal bacterium closely related to the meningococcus, Neisseria meningitidis. Although N. lactamica shares many surface structures with the meningococcus, little is known about the antigenic diversity of this commensal bacterium or the antigenic relationships between N. lactamica and N. meningitidis. Here, the N. lactamica porin protein (Por) was examined and compared to the related PorB antigens of N. meningitidis, to investigate potential involvement in anti-meningococcal immunity. Relationships among porin sequences were determined using distance-based methods and F(ST), and maximum-likelihood analyses were used to compare the selection pressures acting on the encoded proteins. These analyses demonstrated that the N. lactamica porin was less diverse than meningococcal PorB and although it was subject to positive selection, this was not as strong as the positive selection pressures acting on the meningococcal porin. In addition, the N. lactamica porin gene sequences and the protein sequences of the loop regions predicted to be exposed to the human immune system were dissimilar to the corresponding sequences in the meningococcus. This suggests that N. lactamica Por, contrary to previous suggestions, may have limited involvement in the development of natural immunity to meningococcal disease and might not be effective as a meningococcal vaccine component.
Topics: Amino Acid Sequence; Cluster Analysis; DNA, Bacterial; Female; Humans; Infant; Male; Models, Molecular; Molecular Sequence Data; Neisseria lactamica; Neisseria meningitidis; Pharynx; Polymorphism, Genetic; Porins; Selection, Genetic; Sequence Analysis, DNA; Sequence Homology, Amino Acid
PubMed: 18451061
DOI: 10.1099/mic.0.2007/015479-0 -
The Lancet. Microbe Dec 2022Pharyngeal colonisation by the commensal bacterium Neisseria lactamica inhibits colonisation by Neisseria meningitidis and has an inverse epidemiological association... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Pharyngeal colonisation by the commensal bacterium Neisseria lactamica inhibits colonisation by Neisseria meningitidis and has an inverse epidemiological association with meningococcal disease. The mechanisms that underpin this relationship are unclear, but could involve the induction of cross-reactive immunity. In this study, we aimed to evaluate whether colonisation with N lactamica induces N lactamica-specific B-cell responses that are cross-reactive with N meningitidis.
METHODS
In this randomised, placebo-controlled, human infection trial at University Hospital Southampton Clinical Research Facility (Southampton, UK), healthy adults aged 18-45 years were randomly assigned (2:1) to receive intranasal inoculation with either 10 colony-forming units of N lactamica in 1 mL phosphate-buffered saline (PBS) or 1 mL PBS alone. Participants and researchers conducting participant sampling and immunological assays were masked to allocation. The primary endpoint was the frequency of circulating N lactamica-specific plasma cells and memory B cells after N lactamica inoculation (day 7-28) compared with baseline values (day 0), measured using enzyme-linked immunospot assays. The secondary endpoint was to measure the frequency of N meningitidis-specific B cells. In a second study, we measured the effect of duration of N lactamica colonisation on seroconversion by terminating carriage at either 4 days or 14 days with single-dose oral ciprofloxacin. The studies are now closed to participants. The trials are registered with ClinicalTrials.gov, NCT03633474 and NCT03549325.
FINDINGS
Of 50 participants assessed for eligibility between Sept 5, 2018, and March 3, 2019, 31 were randomly assigned (n=20 N lactamica, n=11 PBS). Among the 17 participants who were colonised with N lactamica, the median baselines compared with peak post-colonisation N lactamica-specific plasma-cell frequencies (per 10 peripheral blood mononuclear cells) were 0·0 (IQR 0·0-0·0) versus 5·0 (1·5-10·5) for IgA-secreting plasma cells (p<0·0001), and 0·0 (0·0-0·0) versus 3·0 (1·5-9·5) for IgG-secreting plasma cells (p<0·0001). Median N lactamica-specific IgG memory-B-cell frequencies (percentage of total IgG memory B cells) increased from 0·0024% (0·0000-0·0097) at baseline to 0·0384% (0·0275-0·0649) at day 28 (p<0·0001). The frequency of N meningitidis-specific IgA-secreting and IgG-secreting plasma cells and memory B cells also increased signficantly in participants who were colonised with N lactamica. Upper respiratory tract symptoms were reported in ten (50%) of 20 participants who were inoculated with N lactamica and six (55%) of 11 participants who were inoculated with PBS (p>0·99). Three additional adverse events (two in the N lactamica group and one in the PBS group) and no serious adverse events were reported. In the second study, anti-N lactamica and anti-N meningitidis serum IgG titres increased only in participants who were colonised with N lactamica for 14 days.
INTERPRETATION
Natural immunity to N meningitidis after colonisation with N lactamica might be due to cross-reactive adaptive responses. Exploitation of this microbial mechanism with a genetically modified live vector could protect against N meningitidis colonisation and disease.
FUNDING
Wellcome Trust, Medical Research Council, and NIHR Southampton Biomedical Research Centre.
Topics: Adult; Humans; Neisseria lactamica; Leukocytes, Mononuclear; Neisseria meningitidis; Immunoglobulin A, Secretory; Phosphates; Saline Solution; Immunoglobulin G
PubMed: 36462524
DOI: 10.1016/S2666-5247(22)00283-X -
Journal of Clinical Microbiology Dec 2012Neisseria lactamica is a true commensal bacterium occupying the same ecological niche as the pathogenic Neisseria meningitidis, which is responsible for outbreaks and...
Neisseria lactamica is a true commensal bacterium occupying the same ecological niche as the pathogenic Neisseria meningitidis, which is responsible for outbreaks and large epidemics, especially in sub-Saharan Africa. To better understand the epidemiology of N. lactamica in Africa and its relationship to N. meningitidis, we studied N. lactamica carriage in 1- to 29-year-old people living in three districts of Burkina Faso from 2009 to 2011. N. lactamica was detected in 18.2% of 45,847 oropharyngeal samples. Carriage prevalence was highest among the 2-year-olds (40.1%) and decreased with age. Overall prevalence was higher for males (19.1%) than females (17.5%) (odds ratio [OR], 1.11; 95% confidence interval [CI], 1.04 to 1.18), while among the 18- to 29-year-olds, carriage prevalence was significantly higher in women (9.1%) than in men (3.9%) (OR, 2.49; 95% CI, 1.94 to 3.19). Carriage prevalence of N. lactamica was remarkably homogeneous in the three districts of Burkina Faso and stable over time, in comparison with carriage of N. meningitidis (P. A. Kristiansen et al., Clin. Vaccine Immunol. 18:435-443, 2011). There was no significant seasonal variation of N. lactamica carriage and no significant change in carriage prevalence after introduction of the serogroup A meningococcal conjugate vaccine, MenAfriVac. Multilocus sequence typing was performed on a selection of 142 isolates. The genetic diversity was high, as we identified 62 different genotypes, of which 56 were new. The epidemiology of N. lactamica carriage and the molecular characteristics of carried isolates were similar to those reported from industrialized countries, in contrast to the particularities of N. meningitidis carriage and disease epidemiology in Burkina Faso.
Topics: Adolescent; Adult; Burkina Faso; Carrier State; Child; Child, Preschool; Cross-Sectional Studies; Female; Genetic Variation; Humans; Infant; Male; Molecular Epidemiology; Multilocus Sequence Typing; Neisseria lactamica; Neisseriaceae Infections; Oropharynx; Prevalence; Young Adult
PubMed: 23035186
DOI: 10.1128/JCM.01717-12 -
Antimicrobial Agents and Chemotherapy Jun 2022Invasive meningococcal disease (IMD) due to serogroup Y Neisseria meningitidis (NmY) is rare in China; recently, an invasive NmY isolate, Nm512, was discovered in...
Invasive meningococcal disease (IMD) due to serogroup Y Neisseria meningitidis (NmY) is rare in China; recently, an invasive NmY isolate, Nm512, was discovered in Shanghai with decreased susceptibility to penicillin (Pen). Here, we investigated the epidemiology of NmY isolates in Shanghai and explored the potential commensal Neisseria lactamica donor of the Pen NmY isolate. A total of 491 N. meningitidis and 724 commensal spp. isolates were collected. Eleven NmY isolates were discovered from IMD ( = 1) and carriers ( = 10), including two Pen isolates with five-key-mutation-harboring (F504L-A510V-I515V-H541N-I566V) genes. Five of the eight ST-175 complex (CC175) isolates had a genotype [Y:P1.5-1,2-2:F5-8:ST-175(CC175)] identical to that of the predominant invasive clone found in South Africa. Only one invasive NmY CC23 isolate (Nm512) was discovered; this isolate carried a novel Pen allele, which was identified in commensal N. lactamica isolates locally. Recombination analysis and transformation of the allele highlighted that N. meningitidis Nm512 may acquire resistance from its commensal donor; this was supported by the similar distribution of transformation-required DNA uptake sequence variants and the highly cognate receptor ComP between N. meningitidis and N. lactamica. In 2,309 NmY CC23 genomes from the PubMLST database, isolates with key-mutation-harboring genes comprised 12% and have been increasing since the 1990s, accompanied by recruitment of the and/or quinolone resistance allele. Moreover, was predominant among genomes without key mutations in . These results strongly suggest that Nm512 is a descendant of the -harboring CC23 isolate from Europe and acquired its penicillin resistance locally from commensal N. lactamica species by natural transformation.
Topics: China; Humans; Meningococcal Infections; Neisseria lactamica; Neisseria meningitidis; Neisseria meningitidis, Serogroup Y; Penicillin Resistance; Serogroup
PubMed: 35652645
DOI: 10.1128/aac.02383-21 -
Antimicrobial Agents and Chemotherapy Nov 1990We studied the susceptibilities of relatively penicillin G-resistant and -susceptible strains of Neisseria meningitidis, as well as Neisseria lactamica and Neisseria...
We studied the susceptibilities of relatively penicillin G-resistant and -susceptible strains of Neisseria meningitidis, as well as Neisseria lactamica and Neisseria polysaccharea, to penicillin, ampicillin, and several cephalosporins. The MICs of penicillin, ampicillin, cephalothin, and cefuroxime for moderately resistant meningococci have increased two- to sixfold in relation to MICs for susceptible strains. For these strains of meningococci, N. lactamica, and N. polysaccharea, penicillin, ampicillin, cephalothin, and cefuroxime MICs for 50 and 90% of strains were similar. By genetic transformation of a penicillin-susceptible strain of N. meningitidis to low-level penicillin resistance with DNA from penicillin-resistant strains of N. meningitidis, N. lactamica, N. polysaccharea, and N. gonorrhoeae, isogenic strains with the same pattern of resistance to beta-lactams were obtained, suggesting that these commensal Neisseria spp. could be the source of meningococcal resistance genes.
Topics: Anti-Bacterial Agents; DNA, Bacterial; Drug Resistance, Microbial; Neisseria; Neisseria meningitidis; Penicillin Resistance; Phenotype; Transformation, Genetic; beta-Lactams
PubMed: 2127349
DOI: 10.1128/AAC.34.11.2269 -
Jundishapur Journal of Microbiology Mar 2015Neisseria lactamica as one of the main commensal in oropharynx during the childhood is related to the induction of a natural immunity against meningococcal meningitis....
BACKGROUND
Neisseria lactamica as one of the main commensal in oropharynx during the childhood is related to the induction of a natural immunity against meningococcal meningitis. Also Moraxella catarrhalis in oropharynx of children is a predisposing factor for otitis media infection.
OBJECTIVES
The current study aimed to investigate the frequency of the N. lactamica, other nonpathogenic Neisseria spp. and M. catarrhalis in the oropharynx of young healthy children in Ahvaz, Iran by the two phenotypic tests and Polymerase Chain Reaction (PCR).
MATERIALS AND METHODS
A total of 192 oropharyngeal swab samples of the young healthy children were studied during four months. Swabs were plated onto enriched selective media and non-selective media. Gram-negative and oxidase-positive diplococci were identified by several conventional biochemical tests. The PCR and sequencing were used to confirm the accuracy of laboratory diagnosis to identify N. lactamica and M. catarrhalis.
RESULTS
Among 192 young healthy children with the mean age of 5.93 ± 2.5903 years, authors identified: N. lactamica (21.9%) in the age group of one to nine years; N. mucosa (6.3%); N. sicca (7.8%); N. cinerea (1.6%); N. subflava (biovar subflava) (4.2%); N. subflava (biovar perflava) (28.1%); N. subflava (biovar flava) (7.3%) and M. catarrhalis (42.7%).
CONCLUSIONS
The young healthy children screening by colonization of N. lactamica and other nonpathogenic Neisseria spp. in oropharynx was the first report in Ahvaz, Iran. The study results demonstrated the high frequency of colonization of M. catarrhalis in the studied young healthy children other than Neisseria spp.
PubMed: 25964847
DOI: 10.5812/jjm.14813 -
Current Opinion in Microbiology Oct 2008Advances in high-throughput nucleotide sequencing and bioinformatics make the study of genomes at the population level feasible. Preliminary population genomic studies... (Review)
Review
Advances in high-throughput nucleotide sequencing and bioinformatics make the study of genomes at the population level feasible. Preliminary population genomic studies have explored the relationships among three closely related bacteria, Neisseria meningitidis, Neisseria gonorrhoeae and Neisseria lactamica, which exhibit very different phenotypes with respect to human colonisation. The data obtained have been especially valuable in the establishing of the role of horizontal genetic exchange in bacterial speciation and shaping population structure. In the meningococcus, they have been used to define invasive genetic types, search for virulence factors and potential vaccine components and investigate the effects of vaccines on population structure. These are generic approaches and their application to the Neisseria provides a foretaste for their application to the wider bacterial world.
Topics: Base Sequence; Evolution, Molecular; Gene Transfer, Horizontal; Genetic Variation; Genome, Bacterial; Genomics; Humans; Neisseria gonorrhoeae; Neisseria lactamica; Neisseria meningitidis; Recombination, Genetic; Virulence Factors
PubMed: 18822386
DOI: 10.1016/j.mib.2008.09.002