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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 -
PLoS Pathogens Mar 2020It is increasingly being recognised that the interplay between commensal and pathogenic bacteria can dictate the outcome of infection. Consequently, there is a need to...
It is increasingly being recognised that the interplay between commensal and pathogenic bacteria can dictate the outcome of infection. Consequently, there is a need to understand how commensals interact with their human host and influence pathogen behaviour at epithelial surfaces. Neisseria meningitidis, a leading cause of sepsis and meningitis, exclusively colonises the human nasopharynx and shares this niche with several other Neisseria species, including the commensal Neisseria cinerea. Here, we demonstrate that during adhesion to human epithelial cells N. cinerea co-localises with molecules that are also recruited by the meningococcus, and show that, similar to N. meningitidis, N. cinerea forms dynamic microcolonies on the cell surface in a Type four pilus (Tfp) dependent manner. Finally, we demonstrate that N. cinerea colocalises with N. meningitidis on the epithelial cell surface, limits the size and motility of meningococcal microcolonies, and impairs the effective colonisation of epithelial cells by the pathogen. Our data establish that commensal Neisseria can mimic and affect the behaviour of a pathogen on epithelial cell surfaces.
Topics: A549 Cells; Bacterial Adhesion; Epithelial Cells; Fimbriae, Bacterial; Humans; Neisseria cinerea; Neisseria meningitidis
PubMed: 32208456
DOI: 10.1371/journal.ppat.1008372 -
Communications Biology Nov 2022The CRISPR/Cas9 system is a versatile genome editing platform in biotechnology and therapeutics. However, the requirement of protospacer adjacent motifs (PAMs) limits...
The CRISPR/Cas9 system is a versatile genome editing platform in biotechnology and therapeutics. However, the requirement of protospacer adjacent motifs (PAMs) limits the genome targeting scope. To expand this repertoire, we revisited and engineered a compact Cas9 orthologue derived from Neisseria cinerea (NcCas9) for efficient genome editing in mammal cells. We demonstrated that NcCas9 generates genome editing at target sites with N4GYAT (Y = T/C) PAM which cannot be recognized by existing Cas9s. By optimizing the NcCas9 architecture and its spacer length, editing efficacy of NcCas9 was further improved in human cells. In addition, the NcCas9-derived Base editors can efficiently generate base conversions. Six anti-CRISPR (Acr) proteins were identified as off-switches for NcCas9. Moreover, NcCas9 successfully generated efficient editing of mouse embryos by microinjection of NcCas9 mRNA and the corresponding sgRNA. Thus, the NcCas9 holds the potential to broaden the CRISPR/Cas9 toolsets for efficient gene modifications and therapeutic applications.
Topics: Mice; Humans; Animals; Gene Editing; CRISPR-Cas Systems; CRISPR-Associated Protein 9; Neisseria cinerea; Genome; Mammals
PubMed: 36435853
DOI: 10.1038/s42003-022-04258-z -
Vaccine Dec 2023An affordable, accessible, and broadly protective vaccine is required to tackle the re-occurring bacterial meningococcal epidemics in Sub-Saharan Africa as well as an...
An affordable, accessible, and broadly protective vaccine is required to tackle the re-occurring bacterial meningococcal epidemics in Sub-Saharan Africa as well as an effective control of multi-drug resistant strains of gonococcus. Outer membrane vesicles (OMVs) secreted from Gram-negative bacteria represent an attractive platform for antigen delivery to the immune system and therefore for development of multi-component vaccines. In this study, we describe the generation of modified OMVs (mOMVs) from commensal biosafety-level 1 (BSL-1) Neisseria cinerea ATCC® 14685, which is phylogenetically close to the pathogenic bacteria Neisseria meningitidis and Neisseria gonorrhoeae. mOMVs were prepared from N. cinerea engineered to express heterologous antigens from N. meningitidis (factor H binding protein (fHbp) and Neisseria Heparin Binding Antigen (NHBA-2)) and from N. gonorrhoeae (NHBA-542). Mice immunised with the mOMVs produced antibodies against fHbp and NHBA. The work indicates that mOMV from N. cinerea can be used as a platform to induce immune responses against antigens involved in the protective immune response against meningococcal and gonococcal diseases.
Topics: Mice; Animals; Neisseria cinerea; Bacterial Proteins; Antigens, Bacterial; Neisseria meningitidis; Meningococcal Vaccines; Bacterial Vaccines; Neisseria gonorrhoeae; Immune System; Antibodies, Bacterial
PubMed: 38008665
DOI: 10.1016/j.vaccine.2023.11.034 -
PloS One 2023Neisseria gonorrhoeae is a highly adapted human sexually transmitted pathogen that can cause symptomatic infections associated with localized inflammation as well as...
Neisseria gonorrhoeae is a highly adapted human sexually transmitted pathogen that can cause symptomatic infections associated with localized inflammation as well as asymptomatic and subclinical infections, particularly in females. Gonococcal infection in humans does not generate an effective immune response in most cases, which contributes to both transmission of the pathogen and reinfection after treatment. Neisseria gonorrhoeae is known to evade and suppress human immune responses through a variety of mechanisms. Commensal Neisseria species that are closely related to N. gonorrhoeae, such as N. cinerea, N. lactamica, N. elongata, and N. mucosa, rarely cause disease and instead asymptomatically colonize mucosal sites for prolonged periods of time without evoking clearing immunologic responses. We have shown previously that N. gonorrhoeae inhibits the capacity of antigen-pulsed dendritic cells to induce CD4+ T cell proliferation in vitro. Much of the suppressive effects of N. gonorrhoeae on dendritic cells can be recapitulated either by outer-membrane vesicles released from the bacteria or by purified PorB, the most abundant outer-membrane protein in Neisseria gonorrhoeae. We show here that three commensal Neisseria species, N. cinerea, N. lactamica and N. mucosa, show a comparable capacity to suppress dendritic cell-induced T cell proliferation in vitro through mechanisms similar to those demonstrated previously for N. gonorrhoeae, including inhibition by purified PorB. Our findings suggest that some immune-evasive properties of pathogenic N. gonorrhoeae are shared with commensal Neisseria species and may contribute to the ability of both pathogens and commensals to cause prolonged mucosal colonization in humans.
Topics: Humans; Neisseria; Neisseria gonorrhoeae; Gonorrhea; CD4-Positive T-Lymphocytes; Membrane Proteins
PubMed: 37027389
DOI: 10.1371/journal.pone.0284062 -
MSphere Jun 2021Many bacterial carriage studies utilize colistin-containing media to select for Neisseria meningitidis among the diverse human pharyngeal milieu. These studies commonly...
Many bacterial carriage studies utilize colistin-containing media to select for Neisseria meningitidis among the diverse human pharyngeal milieu. These studies commonly report the isolation of commensal species, with carriage rates of around 1% or less typically observed. Here, we describe the isolation of N. cinerea and N. polysaccharea from pharyngeal swabs using nonselective agar and confirm they are unable to grow on colistin-containing media. We also demonstrated colistin sensitivity among archived commensal strains, including , N. polysaccharea, N. mucosa, and N. subflava. The distribution of among these strains indicated that, while the phosphoethanolamine (PEA) transferase encoded by this gene confers colistin resistance, other mechanisms may lead to reduced susceptibility in some deficient strains. The majority of the and N. polysaccharea isolates expressed medium to very high levels of factor H-binding protein (fHbp), an important meningococcal vaccine antigen. Sequence analysis showed that the commensal fHbp peptide variants were similar in sequence to fHbp variants typically observed among invasive meningococci. Altogether, these results not only suggest that commensal strains could be carried at much higher rates than previously reported but also raise questions about the impact of protein-based meningococcal vaccines on these unencapsulated commensals. This study highlights the need for further work to accurately determine the pharyngeal carriage prevalence of commensal bacteria (e.g., and N. polysaccharea) among the general population. Previous studies have clearly demonstrated the suppressive effect these commensal species can have on meningococcal colonization, and so the carriage prevalence of these species could be an important factor in the spread of meningococci through the population. Furthermore, the surface expression of the meningococcal vaccine antigen factor H-binding protein by many of these commensal strains could have important implications for the use of fHbp-containing vaccines. Carriage of these commensal species may influence the immune response to these vaccines, or conversely, the immune response elicited by vaccination may induce clearance of these potentially important members of the pharyngeal niche.
PubMed: 34133203
DOI: 10.1128/mSphere.00175-21 -
Scientific Reports Apr 2022Tobacco use is the leading preventable cause of cancer, and affects the respiratory, oral, fecal, and duodenal mucosa-associated microbiota. However, the effects of...
Tobacco use is the leading preventable cause of cancer, and affects the respiratory, oral, fecal, and duodenal mucosa-associated microbiota. However, the effects of smoking on the duodenal luminal microbiome have not been studied directly. We aimed to compare the duodenal luminal microbiome in never-smokers, current smokers, and ex-smokers who quit ≥ 10 years ago. In a cross-sectional study, current smokers (CS, n = 24) were identified and matched to never-smokers (NS, n = 27) and ex-smokers (XS, n = 27) by age (± 5 years), body mass index (BMI, ± 3 kg/m), and sex. Current antibiotic users were excluded. The duodenal luminal microbiome was analysed in 1 aspirate sample per subject by 16S rRNA gene sequencing. Relative abundances (RA) of families associated with increased duodenal microbial diversity, Prevotellaceae, Neisseriaceae, and Porphyromonadaceae, were significantly lower in CS vs. NS. This was driven by lower RA of unknown Prevotella and Porphyromonas species, and Neisseria subflava and N. cinerea, in CS. In contrast, RA of Enterobacteriaceae and Lactobacillaceae (associated with decreased diversity), were significantly higher in CS, due to higher RA of Escherichia-Shigella, Klebsiella and Lactobacillus species. Many of these changes were absent or less pronounced in XS, who exhibited a duodenal luminal microbiome more similar to NS. RA of taxa previously found to be increased in the oral and respiratory microbiota of smokers were also higher in the duodenal luminal microbiome, including Bulledia extructa and an unknown Filifactor species. In conclusion, smoking is associated with an altered duodenal luminal microbiome. However, ex-smokers have a duodenal luminal microbiome that is similar to never-smokers.
Topics: Cross-Sectional Studies; Humans; Microbiota; RNA, Ribosomal, 16S; Smoking; Tobacco Smoking
PubMed: 35422064
DOI: 10.1038/s41598-022-10132-z -
Journal of Clinical Microbiology May 1988Neisseria cinerea is a commensal Neisseria sp. which was first described in 1906 but was subsequently misclassified as a subtype of Branhamella catarrhalis. N. cinerea...
Neisseria cinerea is a commensal Neisseria sp. which was first described in 1906 but was subsequently misclassified as a subtype of Branhamella catarrhalis. N. cinerea resembles Neisseria gonorrhoeae in both cultural and biochemical characteristics and, thus, may also have been misidentified as N. gonorrhoeae. Of 202 patients whose oropharynges were colonized by Neisseria spp., N. cinerea was isolated in 57 (28.2%) patients, including 25 (30.1%) of 83 women, 22 (23.9%) of 92 heterosexual men, and 10 (37.0%) of 27 homosexual men in Seattle, Wash., in 1983 to 1984. N. cinerea was isolated from the urethra of only one (1.1%) patient. The oropharynges of many individuals were colonized persistently by strains of N. cinerea and other Neisseria spp.
Topics: Cervix Uteri; Culture Media; Female; Homosexuality; Humans; Male; Neisseria; Oropharynx; Urethra
PubMed: 3384913
DOI: 10.1128/jcm.26.5.896-900.1988 -
Genome Biology and Evolution Feb 2020Neisseria spp. possess four genogroups of filamentous prophages, termed Nf1 to 4. A filamentous bacteriophage from the Nf1 genogroup termed meningococcal...
Neisseria spp. possess four genogroups of filamentous prophages, termed Nf1 to 4. A filamentous bacteriophage from the Nf1 genogroup termed meningococcal disease-associated phage (MDA φ) is associated with clonal complexes of Neisseria meningitidis that cause invasive meningococcal disease. Recently, we recovered an isolate of Neisseria gonorrhoeae (ExNg63) from a rare case of gonococcal meningitis, and found that it possessed a region with 90% similarity to Nf1 prophages, specifically, the meningococcal MDA φ. This led to the hypothesis that the Nf1 prophage may be more widely distributed amongst the genus Neisseria. An analysis of 92 reference genomes revealed the presence of intact Nf1 prophages in the commensal species, Neisseria lactamica and Neisseria cinerea in addition to the pathogen N. gonorrhoeae. In N. gonorrhoeae, Nf1 prophages had a restricted distribution but were present in all representatives of MLST ST1918. Of the 160 phage integration sites identified, only one common insertion site was found between one isolate of N. gonorrhoeae and N. meningitidis. There was an absence of any obvious conservation of the receptor for prophage entry, PilE, suggesting that the phage may have been obtained by natural transformation. An examination of the restriction modification systems and mutated mismatch repair systems with prophage presence suggested that there was no obvious preference for these hosts. A timed phylogeny inferred that N. meningitidis was the donor of the Nf1 prophages in N. lactamica and N. gonorrhoeae. Further work is required to determine whether Nf1 prophages are active and can act as accessory colonization factors in these species.
Topics: Gene Transfer, Horizontal; Inovirus; Meningococcal Infections; Neisseria; Neisseria cinerea; Neisseria gonorrhoeae; Neisseria lactamica; Phylogeny; Prophages
PubMed: 32031617
DOI: 10.1093/gbe/evaa023 -
Cureus Mar 2021is a commensal bacteria of the human oropharynx, not thought to be pathogenic, and is rarely associated with serious infections, including bacteremia. Case reports...
is a commensal bacteria of the human oropharynx, not thought to be pathogenic, and is rarely associated with serious infections, including bacteremia. Case reports involving invasive infections are uncommon in the literature. Retropharyngeal abscesses are unusual in adults, and are usually attributable to local trauma.Based on a review of the literature, bacteremia secondary to a retropharyngeal abscess has not been described. We present a unique case of an elderly female without clear predisposing factors for a retropharyngeal abscess, who presented with a bacteremia and was found to have an asymptomatic retropharyngeal abscess.
PubMed: 33948407
DOI: 10.7759/cureus.14217