Neisseria flava

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Classification

Higher order taxa

Bacteria-Proteobacteria- β-proteobacteria-Neisseriales-Neisseriaceae-Neisseria ^[1]

Species

Neisseria flava strain NRL 30,008  [2]

Some authors and some of the old literatures may refer “N. flava” as “Diplococcus pharyngis flavus” group I, Chromogenic group I, Chromogenic group 4, Strain Fb, “Neisseria pharynges”, “N. subflava” and “N. subflava (biovarflava)” ^[4].

Description and significance

“N. flava” is a saccharolytic, Gram-negative, oxidase positive, diplococcal bacteria ^[3]. The organism is one of the commensal flora that inhabit oropharynx and nasopharynx. “N. flava” is considered a non-pathogenic “Neisseria” species, but it can also be opportunistic pathogen in human. In the early 1900s, the classification of saccharolytic commensal “Neisseria” spp. were based on cell morphology and their patterns of acid production from carbohydrates ^[4]. However, due to the inability of the identification techniques to clearly distinguish the commensal “Neisseria” spp., “N. flava”, “N. perflava” and “N. subflava” were later grouped together as a single species “N. subflava” (biovars), and “N. flava” may be referred as “N. subflava” biovar “flava” ^[3]. The bacteria can be cultured traditionally on Chocolate, blood agar and nutrient agar at 22 oC and 35 oC respectively ^[4]. The biochemical and cultural characteristics of “N. flava” include ^[5].;

• Inability to produce polysaccharide from sucrose
• Acid production from fructose (fructose positive)
• Ammonia production from peptone
• Susceptibility to colistin (unable to grow on gonococcal selective media)
• Ability to reduce nitrite (NO2)
• The colonies are flat pigmented opaque with matt appearance

“Neisseriae” are one of the most abundant commensal flora in human that in rare occasions can cause pathogenesis in human, therefore it is important to understand whether the non-pathogenic commensal “Neisseria” spp. could contribute to the pathogenicity of the pathogenic strains as seen in “N. gonorrhoeae” and “N. meningitidis”.

Figure 1. Electron micrograph of “N. subflava” with diplococcal structure ^[3]

Genome structure

Using illumine Hiseq 2000 platform, the genome of “N. flava” (strain NRL 30,008) has been sequenced having a genome size of 243.7 Mbp with 49% GC content. ^[2].

Cell structure and metabolism

Just like other gram-negative bacteria, “N. flava” has subcapsular cell envelope that made up of an outer membrane (OM), a single thin layer of peptidoglycan and an inner cell membrane ^[3]. The lipopolysaccharide (LPS) component of the OM is in fact a lipooligosaccharide (LOS) ^[6]. In the pathogenic strains, LOS is an outer membrane glycolipid that is found to be associated with the cells evasion, attachment, invasion and mediation of toxic damage to the host. LOS consists of O-antigen, core-oligosaccharide and lipid-A. Three types of core-oligosaccharide, Type-I – III, that have been established and are distinguishable between non-pathogenic from pathogenic “Neisseria” species. “N. flava” possess R-configuration of lipopolysaccharide (LPS) and type-II core oligosaccharide, which made up of D-glucose (3 mol), 2-deoxy-2-amino-Dglucose (2 mol), L-rhamnose (1 mol), L-glyceroD-manno-heptose (I mol), and ethanolamine (I mol) ^[7]. There has been much extensive research to study the expression of Neisserial pili in the commensal “Neisseria”. Pili can be observed in “N. flava” under electron micrograph ^[8]. However, the organism did not react to monoclonal antibodies specific for SM1 epitope that recognise Class-I pili, suggested that this species may possess other type of pilli that are distinct from pile of the pathogenic strains ^[8][9]. Currently there are limited direct studies on the metabolism of “Neisseria”. However, in the laboratory setting, “N. flava” is able to reduce nitrite (NO2) and oxidatively utilise carbohydrates (glucose, maltose, fructose, but not sucrose and lactose) as its energy sources (4). For sufficient growth in the synthetic media, “N. flava” require biotin, glutamic acid, five amino acids (Cysteine, Isoleucine, Glutamic acid, Phenylalanine and Proline) and lactate. Similar to gram positive aerobic bacteria “N. flava” excretes large amount of ammonia when growing in the presence of amino acids ^[10].

Ecology

Like other “Neisseria” spp., “N. flava” is an aerobic β-proteobacteria ^[3]. The organism inhabits the upper respiratory tract of human ^[3]. There is no extensive study of “N. flava” and its host range, however, the organism has been identified in the oropharyngeal of rhesus macaques, which suggests that this species is not host restrict to only human ^[11].

Pathology

“N. flava” has been rarely documented to caused bacterial endocarditis ^[12]. However, cardiac lesion has been shown to be the main predisposition of the infection. The organism has also been recorded for its causal association with meningitis and genital tract infection ^[13]. It is of interest for future research to explore the strategies that this organism could employ to escapes from its usual habitats, evade and resist the host immune surveillance systems, as well as whether this organism can readily colonise these other tissues when compared to its usual habitats. Iron acquisition is essential for the survival of microorganism. In human host, heme is the main iron source for the microorganisms inhabiting human body. A heme oxygenase (HmuO) homolog has been identified from six “Neisseria” isolates including “N. flava” ^[14]. It was the first discovery of “hmuO” gene identified in gram negative bacteria. The finding showed that oxidative cleavage of the porphyrin is a crucial step of heme utilisation in “Neisseria” and this could be another mechanism for iron acquisition in some bacteria. Apart from heme-iron assimilation, the products of heme degradation by HmuO, mainly biliverdin and CO, also provide protection against oxidative damage and heme toxicity.The reduction of biliverdin can serve as a powerful antioxidant, while the binding of CO to eukaryotic guanylyl cyclase can increases the availability of intracellular cGMP. HemO-dependent heme degradation may interfere with the function of polymorphonuclear leukocytes and host circulatory systems, which could contribute to the infection in female during the onset of menstruation period ^[14].

Application to biotechnology

Apart from its usage as one of the representative commensal “Neisseria” spp., there are limited usages of this species by itself. However, there are numbers of evidence which suggest that the abundance and microbial diversity of the commensal “Neisseria” correlate with some human diseases ^[15], ^[16], ^[17], ^[18]. And that the oral microbiome profile of commensal “Neisseria” could potentially be used as biomarkers for human diseases ^[11].

Current research

It has been shown that “Neisseria” is capable of exchanging their genetic materials both intra- and interspecies ^[19], ^[20], ^[21], ^[22]. Examples that mediate the genetic exchange event such as horizontal gene transfer via plasmid transformation and DNA uptake sequence that allow homologous recombination of the genetic material from extracellular environment. Comparative sequence analysis of the commensal “Neisseria” spp. indicated that the commensal species possess large sets of virulence gene. Numbers of evidence suggested that non-pathogenic “Neisseriaceae” possess homologous virulence genes found in the pathogenic strains such as “opa” gene and lipooligosaccharide which are one of the important virulence factors that are responsible for host immune evasion ^[23]. It has been shown that “N. flava” possess two copies of “opa” gene, adhesive proteins that highly constitute the outer membrane, that share strong homology to opa genes found in the pathogenic “Neisseria” strains ^[24], ^[25]. The homologous gene variants that are shared between the pathogenic and non-pathogenic strains may serve as a reservoir for virulence- and or antimicrobial resistant gene variants, which may indirectly contribute to pathogenic potential of both strains. Questions have been raised for why do the commensal not cause pathogenesis? and how do they evade the host immune surveillance systems given the repertoire of virulence genes?

References

1. [1] 2. [2] 3. (2015) Chapter 5 - Oral Mucosal Microbes, p 95-107, Atlas of Oral Microbiology doi:https://doi.org/10.1016/B978-0-12-802234-4.00005-7. Academic Press, Oxford. 4. Knapp JS. (1988) Historical perspectives and identification of Neisseria and related species. Clinical Microbiology Reviews 1:415-431. 5. Knapp JS, Hook EW, 3rd. (1988) Prevalence and persistence of Neisseria cinerea and other Neisseria spp. in adults. J Clin Microbiol 26:896-900. 6. Nikaido H. (1999) Microdermatology: cell surface in the interaction of microbes with the external world. Journal of bacteriology 181:4-8. 7. Johnson KG, Perry MB, McDonald IJ. (1976) Studies of the cellular and free lipopolysaccharides form Neisseria canis and N. subflava. Can J Microbiol 22:189-96. 8. Aho EL, Murphy GL, Cannon JG. (1987) Distribution of specific DNA sequences among pathogenic and commensal Neisseria species. Infect Immun 55:1009-13. 9. Hung M-C, Christodoulides M. (2013) The Biology of Neisseria Adhesins. Biology 2:1054-1109. 10. McDonald IJ, Johnson KG. (1975) Nutritional requirements of some non-pathogenic Neisseria grown in simple synthetic media. Can J Microbiol 21:1198-204. 11. Liu G, Tang CM, Exley RM. (2015) Non-pathogenic Neisseria: members of an abundant, multi-habitat, diverse genus. Microbiology 161:1297-1312. 12. Scott RM. (1971) Bacterial endocarditis due to Neisseria flava. The Journal of Pediatrics 78:673-675. 13. AP. (1983) The pathogenic potential of commensal species of Neisseria. Journal of Clinical Pathology 36:213-223. 14. Zhu W, Wilks A, Stojiljkovic I. (2000) Degradation of heme in gram-negative bacteria: the product of the hemO gene of Neisseriae is a heme oxygenase.(Statistical Data Included). Journal of Bacteriology 182:6783. 15. Curtis Michael A, Zenobia C, Darveau Richard P. The Relationship of the Oral Microbiotia to Periodontal Health and Disease. Cell Host & Microbe 10:302-306. 16. Filkins LM, Hampton TH, Gifford AH, Gross MJ, Hogan DA, Sogin ML, Morrison HG, Paster BJ, O'Toole GA. (2012) Prevalence of streptococci and increased polymicrobial diversity associated with cystic fibrosis patient stability. Journal of bacteriology 194:4709-4717. 17. Said HS, Suda W, Nakagome S, Chinen H, Oshima K, Kim S, Kimura R, Iraha A, Ishida H, Fujita J, Mano S, Morita H, Dohi T, Oota H, Hattori M. (2014) Dysbiosis of Salivary Microbiota in Inflammatory Bowel Disease and Its Association With Oral Immunological Biomarkers. DNA Research 21:15-25. 18. Farrell JJ, Zhang L, Zhou H, Chia D, Elashoff D, Akin D, Paster BJ, Joshipura K, Wong DTW. (2011) Variations of oral microbiota are associated with pancreatic diseases including pancreatic cancer. Gut. 19. Marri PR, Paniscus M, Weyand NJ, Rendón MA, Calton CM, Hernández DR, Higashi DL, Sodergren E, Weinstock GM, Rounsley SD, So M. 2010. Genome Sequencing Reveals Widespread Virulence Gene Exchange among Human Neisseria Species. PLOS ONE 5:e11835. 20. Zhou J, Bowler LD, Spratt BG. 1997. Interspecies recombination, and phylogenetic distortions, within the glutamine synthetase and shikimate dehydrogenase genes of Neisseria meningitidis and commensal Neisseria species. Molecular Microbiology 23:799-812. 21. van Passel MWJ, van der Ende A, Bart A. 2006. Plasmid Diversity in Neisseriae. Infection and Immunity 74:4892. 22. eil E, Zhou J, Smith JM, Spratt BG. 1996. A comparison of the nucleotide sequences of theadk andrecA genes of pathogenic and commensalNeisseria species: Evidence for extensive interspecies recombination withinadk. Journal of Molecular Evolution 43:631-640. 23. Toleman M, Aho E, Virji M. (2001) Expression of pathogen-like Opa adhesins in commensal Neisseria: genetic and functional analysis. Cellular Microbiology 3:33-44. 24. Wolff K, Stern A. (1995) Identification and characterization of specific sequences encoding pathogenicity associated proteins in the genome of commensal Neisseria species. FEMS Microbiology Letters 125:255-263. 25. Roberts MC, Chung WO, Roe D, Xia M, Marquez C, Borthagaray G, Whittington WL, Holmes KK. (1999) Erythromycin-Resistant Neisseria gonorrhoeae and Oral Commensal Neisseria spp. Carry Known rRNA Methylase Genes. Antimicrobial Agents and Chemotherapy 43:1367.

This page is written by <Pawat Laohamonthonkul (43895212)> for the MICR3004 course, Semester 2, 2017