Neisseria is a large genus of bacteria that colonize the mucosal
surfaces of many animals. Of the 11 species that colonize humans, only
two are pathogens,
N. meningitidis and N. gonorrhoeae. Most gonoccocal
infections are asymptomatic and self-resolving, and epidemic strains
of the meningococcus may be carried in >95% of a population where
systemic disease occurs at <1% prevalence.
Neisseria species are
Gram-negative bacteria included among the
proteobacteria, a large group of
Gram-negative forms. Neisseria
diplococci resemble coffee beans when viewed microscopically.
3 Biochemical identification
5 Iron acquisition
Pathogens acquire iron by two different strategies
7 Antibiotic resistance
8 Genetic transformation
Neisseria is named after the German bacteriologist Albert
Neisser, who in 1879 discovered its first example, Neisseria
gonorrheae, the pathogen which causes the human disease gonorrhea.
Neisser also codiscovered the pathogen that causes leprosy,
Mycobacterium leprae. These discoveries were made possible by the
development of new staining techniques which he helped to develop.
This genus (family Neisseriaceae) of parasitic bacteria grow in pairs
and occasionally tetrads, and thrive best at 98.6 °F
(37 °C) in the animal body or serum media.
The genus includes:
N. gonorrhoeae (also called the gonococcus), which causes gonorrhea.
N. meningitidis (also called the meningococcus), one of the most
common causes of bacterial meningitis and the causative agent of
These two species have the ability of 'breaching' the barrier. Local
cytokines of the area become secreted to initiate an immune response.
However, neutrophils are not able to do their job due to the ability
Neisseria to invade and replicate within neutrophils, as well
avoiding phagocytosis and being killed by complement by resisting
opsonization by antibodies, which target the pathogen for destruction.
Neisseria species are also able to alter their antigens to avoid being
engulfed by a process called antigenic variation, which is observed
primarily in surface-located molecules. The pathogenic species along
with some commensal species, have type IV pili which serve multiple
functions for this organism. Some functions of the type IV pili
include: mediating attachment to various cells and tissues, twitching
motility, natural competence, microcolony formation, extensive
intrastrain phase, and antigenic variation.
Neisseria bacteria have also been shown to be an important factor in
the early stages of canine plaque development.
Phylogenetic tree of selected
Neisseria species, based on
concatenating the DNA sequences of all 896 core
Neisseria genes. From
Marri et al. 2010.
This genus also contains several, believed to be commensal, or
However, some of these can be associated with disease.
All the medically significant species of
Neisseria are positive for
both catalase and oxidase. Different
Neisseria species can be
identified by the sets of sugars from which they will produce acid.
For example, N. gonorrheae makes acid from only glucose, but N.
meningitidis produces acid from both glucose and maltose.
N. meningitidis has a polysaccharide capsule
that surrounds the outer membrane of the bacterium and protects
against soluble immune effector mechanisms within the serum. It is
considered to be an essential virulence factor for the bacteria. N.
gonorrhea possesses no such capsule. Instead of having the usual
lipopolysaccharide (LPS), this bacterium, whether a pathogenic or
commensal species, has a lipooligosaccharide (LOS) which consists of a
core polysaccharide and lipid A. It functions as an endotoxin,
protects against antimicrobial peptides, and adheres to the
asialoglycoprotein receptor on urethral cells. LOS is highly
stimulatory to the human immune system. LOS sialylation (by the
enzyme's Lst) prevents complement deposition and phagocytosis by
neutrophils. LOS modification by phosphoethanolamine (by the enzyme
LptA) provides resistance to antimicrobial peptides and complement.
Strains of the same species have the ability to produce different LOS
The genomes of at least 10
Neisseria species have been completely
sequenced. The best-studied species are
N. meningitidis with more
than 70 strains and
N. gonorrhoeae with at least 10 strains completely
sequenced. Other complete genomes are available for N. elongata, N.
lactamica, and N. weaveri. Whole genome shotgun sequences are
available for hundreds of other species and strains. N.
meningitidis encodes 2,440 to 2,854 proteins while N. gonorrhoeae
encodes from 2,603 to 2,871 proteins. N. weaveri (strain NCTC 13585)
has the smallest known genome with only 2,060 encoded proteins
N. meningitidis MC58 has been reported to have only 2049
genes. The genomes are generally quite similar. For example, when
the genome of
N. gonorrhoeae (strain FA1090) is compared to that of N.
meningitidis (strain H44/76) 68% of their genes are shared.
Genome properties of
N. lactamica 23970
N. gonorrhoeae FA1090
N. meningitidis MC58
Iron is absolutely required by all life forms, playing a critical role
in a number of essential processes. Free iron, at least what would be
readily available to a microbial pathogen, practically does not exist
in animals. In vertebrates, the majority of iron is stored inside
cells in complex with either ferritin or hemoglobin. Extracellular
iron is found in body fluids complexed to either transferrin or
Pathogens acquire iron by two different strategies
‘Siderophore’-mediated iron uptake involves outcompeting
transferrin and/or lactoferrin for iron binding. Iron-bound
siderophores are then taken into the bacterium by specific receptors.
Direct uptake of iron-bound host proteins involves the bacteria
possessing a high affinity for transferrin, lactoferrin, and
hemoglobin (the approach used by the pathogenic Neiserria spp.).
Receptors: HmbRm, HpuA, and HpuB are receptors for
haptoglobin-haemoglobin. LbpAB is a receptor for human lactoferrin.
TbpAB (Tbp1-Tbp2) is a receptor for human transferrin. All of these
receptors are used for iron acquisition for both pathogenic and
Diseases caused by
N. meningitidis and
N. gonorrhoeae are significant
health problems worldwide, the control of which is largely dependent
on the availability and widespread use of comprehensive meningococcal
and gonococcal vaccines. Development of neisserial vaccines has been
challenging due to the nature of these organisms, in particular the
heterogeneity, variability and/or poor immunogenicity of their outer
surface components. As strictly human pathogens, they are highly
adapted to the host environment, but have evolved several mechanisms
to remain adaptable to changing microenvironments and avoid
elimination by the host immune system. Currently, serogroup A, B, C,
Y, and W-135 meningococcal infections can be prevented by vaccines.
However, the prospect of developing a gonococcal vaccine is
The acquisition of cephalosporin resistance in N. gonorrhoeae,
particularly ceftriaxone resistance, has greatly complicated the
treatment of gonorrhea, with the gonococcus now being classified as a
Genetic transformation is the process by which a recipient bacterial
cell takes up DNA from a neighboring cell and integrates this DNA into
the recipient’s genome by recombination. In N. meningitides and N.
gonorrhoeae, DNA transformation requires the presence of short DNA
sequences (9-10 monomers residing in coding regions) of the donor DNA.
These sequences are called DNA uptake sequences (DUSs). Specific
recognition of DUSs is mediated by a type IV pilin. Davidsen et
al. reported that in N. meningitides and N. gonorrhoeae, DUSs
occur at a significantly higher density in genes involved in DNA
repair and recombination (as well as in restriction-modification and
replication) than in other annotated gene groups. These authors
proposed that the over-representation of DUS in
DNA repair and
recombination genes may reflect the benefit of maintaining the
integrity of the
DNA repair and recombination machinery by
preferentially taking up genome maintenance genes that could replace
their damaged counterparts in the recipient cell. Caugant and Maiden
noted that the distribution of DUS is consistent with recombination
being primarily a mechanism for genome repair that can occasionally
result in generation of diversity, which even more occasionally, is
adaptive. It was also suggested by Michod et al. that an
important benefit of transformation in
N. gonorrhoeae is
recombinational repair of oxidative DNA damages caused by oxidative
attack by the host’s phagocytic cells.
Neisseria Conference (IPNC), occurring
every two years, is a forum for the presentation of cutting-edge
research on all aspects of the genus Neisseria. This includes
immunology, vaccinology, and physiology and metabolism of N.
N. gonorrhoeae and the commensal species. The first IPNC
took place in 1978, and the most recent one was in September 2016.
Normally, the location of the conference switches between North
America and Europe, but it took place in Australia for the first time
in 2006, where the venue was located in Cairns.
^ Ryan KJ; Ray CG, eds. (2004). Sherris Medical Microbiology (4th
ed.). McGraw Hill. ISBN 0-8385-8529-9.
^ Early Canine Plaque Biofilms: Characterization of Key Bacterial
Interactions Involved in Initial Colonization of Enamel. Lucy J.
Holcombe, Niran Patel, Alison Colyer, Oliver Deusch, Ciaran O’Flynn,
Stephen Harris. PLoS One, 2014.
^ a b c d Marri, Pradeep Reddy; Paniscus, Mary; Weyand, Nathan J.;
Rendón, María A.; Calton, Christine M.; Hernández, Diana R.;
Higashi, Dustin L.; Sodergren, Erica; Weinstock, George M.
Genome Sequencing Reveals Widespread Virulence Gene
Exchange among Human
Neisseria Species". PLOS ONE. 5 (7): e11835.
doi:10.1371/journal.pone.0011835. ISSN 1932-6203.
PMC 2911385 . PMID 20676376.
^ Tronel H, Chaudemanche H, Pechier N, Doutrelant L, Hoen B (May
2001). "Endocarditis due to
Neisseria mucosa after tongue piercing".
Clin. Microbiol. Infect. 7 (5): 275–6.
doi:10.1046/j.1469-0691.2001.00241.x. PMID 11422256.
^ Ullrich, M, ed. (2009). Bacterial Polysaccharides: Current
Innovations and Future Trends. Caister Academic Press.
^ Minogue, T. D.; Daligault, H. A.; Davenport, K. W.; Bishop-Lilly, K.
A.; Bruce, D. C.; Chain, P. S.; Chertkov, O.; Coyne, S. R.; Freitas,
T. (2014-09-25). "Draft
Genome Assembly of
Neisseria lactamica Type
Genome Announcements. 2 (5).
doi:10.1128/genomeA.00951-14. PMC 4175205 .
^ a b "
Neisseria in the PATRIC database". PATRIC. 2017-02-26.
^ Alexander, Sarah; Fazal, Mohammed-Abbas; Burnett, Edward;
Deheer-Graham, Ana; Oliver, Karen; Holroyd, Nancy; Parkhill, Julian;
Russell, Julie E. (2016-08-25). "Complete
Genome Sequence of Neisseria
weaveri Strain NCTC13585".
Genome Announcements. 4 (4).
doi:10.1128/genomeA.00815-16. PMC 5000823 .
^ "meningococcal group B vaccine". Medscape. WebMD. Retrieved December
^ Seib KL, Rappuoli R (2010). "Difficulty in Developing a Neisserial
Vaccine". Neisseria: Molecular Mechanisms of Pathogenesis. Caister
Academic Press. ISBN 978-1-904455-51-6.
^ Unemo M, Nicholas RA (December 2012). "Emergence of
multidrug-resistant, extensively drug-resistant and untreatable
gonorrhea". Future Microbiol. 7 (12): 1401–1422.
doi:10.2217/fmb.12.117. PMC 3629839 . PMID 23231489.
^ Cehovin A, Simpson PJ, McDowell MA, Brown DR, Noschese R, Pallett M,
Brady J, Baldwin GS, Lea SM, Matthews SJ, Pelicic V (2013). "Specific
DNA recognition mediated by a type IV pilin". Proc. Natl. Acad. Sci.
U.S.A. 110 (8): 3065–70. doi:10.1073/pnas.1218832110.
PMC 3581936 . PMID 23386723.
^ Davidsen T, Rødland EA, Lagesen K, Seeberg E, Rognes T, Tønjum T
(2004). "Biased distribution of DNA uptake sequences towards genome
maintenance genes". Nucleic Acids Res. 32 (3): 1050–8.
doi:10.1093/nar/gkh255. PMC 373393 . PMID 14960717.
^ Caugant DA, Maiden MC (2009). "Meningococcal carriage and
disease--population biology and evolution". Vaccine. 27 Suppl 2:
B64–70. doi:10.1016/j.vaccine.2009.04.061. PMC 2719693 .
^ Michod RE, Bernstein H, Nedelcu AM (2008). "Adaptive value of sex in
microbial pathogens". Infect. Genet. Evol. 8 (3): 267–85.
doi:10.1016/j.meegid.2008.01.002. PMID 18295550.