Elizabethkingia meningoseptica: Difference between revisions

From MicrobeWiki, the student-edited microbiology resource
No edit summary
No edit summary
Line 28: Line 28:
Initially thought the same species, Elizabethkingia anophelis ribosomal 16S was 98% identical to that of E.  meningoseptica [[#References |[5]]]. However, additional findings suggest that due to significant differences in protein coding regions, they are two separate species [[#References |[5]]].
Initially thought the same species, Elizabethkingia anophelis ribosomal 16S was 98% identical to that of E.  meningoseptica [[#References |[5]]]. However, additional findings suggest that due to significant differences in protein coding regions, they are two separate species [[#References |[5]]].


=Genes of Interest=
==Genes of Interest==
Gene BFF93_RS16990, a member of the CDC family, was found in E.  meningoseptica [[#References |[6]]]. Although usually found in pathogenic Gram-positive bacteria, this CDC gene is a major virulence factor of E.  meningoseptica [[#References |[6]]]. CDC genes generally allow the transport of protein into host cells, many of which transport hemolysin, an enzyme that can potentially kill host erythrocytes [[#References |[6]]]. Additionally, this CDC gene was found downstream of hmuY gene which is responsible for iron metabolism; this hints toward erythrocytes as E. meningoseptica’s primary or potentially its only source of iron and nutrients hence its pathogenicity in bloodstreams [[#References |[6]]]. Furthermore, this CDC gene encodes for perfringolysin, a cytotoxic and leukostasis toxin that allows the evasion of phagocytic activity of host immune systems [[#References |[5]]],[[#References |[6]]].
Gene BFF93_RS16990, a member of the CDC family, was found in E.  meningoseptica [[#References |[6]]]. Although usually found in pathogenic Gram-positive bacteria, this CDC gene is a major virulence factor of E.  meningoseptica [[#References |[6]]]. CDC genes generally allow the transport of protein into host cells, many of which transport hemolysin, an enzyme that can potentially kill host erythrocytes [[#References |[6]]]. Additionally, this CDC gene was found downstream of hmuY gene which is responsible for iron metabolism; this hints toward erythrocytes as E. meningoseptica’s primary or potentially its only source of iron and nutrients hence its pathogenicity in bloodstreams [[#References |[6]]]. Furthermore, this CDC gene encodes for perfringolysin, a cytotoxic and leukostasis toxin that allows the evasion of phagocytic activity of host immune systems [[#References |[5]]],[[#References |[6]]].
Gene BFF93_RS1398 was also found in E.  meningoseptica. Common in pathogenic bacteria, BFF93_RS1398 encodes hemagglutinins, proteins used by many invasive bacteria as adhesive elements onto host cells [[#References |[5]]]. Evidence of additional operons involved in curli biosynthesis was also found in clinical strains which not only allowed increase biofilm production, but also increase is cell attachment and aggregation [[#References |[6]]].
Gene BFF93_RS1398 was also found in E.  meningoseptica. Common in pathogenic bacteria, BFF93_RS1398 encodes hemagglutinins, proteins used by many invasive bacteria as adhesive elements onto host cells [[#References |[5]]]. Evidence of additional operons involved in curli biosynthesis was also found in clinical strains which not only allowed increase biofilm production, but also increase is cell attachment and aggregation [[#References |[6]]].


=Metallo-β-Lactamase Genes=
==Metallo-β-Lactamase Genes==
Production of Metallo-β-Lactamases (MBLs) was detected in all clinical strains [[#References |[7]]]. Up to 13 unique blaB and 17 blaGOB  genes were identified, of which, 5 of blaB and 10 of blaGOB were discovered recently and contribute up to 2-4 times higher minimal inhibitory concentrations (MICs) of β-Lactamases such as imipenem and meropenem [[#References |[7]]]. Resistance to common β-Lactamases antibiotics is likely due to the expression of most blaB and GOB genes as many of which are broad spectrum MBLs [[#References |[8]]]. Studies on the expression of MBL genes shows that in poor growing conditions and environments with β-Lactamase antibiotics, expression of MBLs increased [[#References |[8]]]. Evidence for induction of Bla genes by other Bla genes, bolA, and ampR genes is also observed although not conclusive [[#References |[8]]].
Production of Metallo-β-Lactamases (MBLs) was detected in all clinical strains [[#References |[7]]]. Up to 13 unique blaB and 17 blaGOB  genes were identified, of which, 5 of blaB and 10 of blaGOB were discovered recently and contribute up to 2-4 times higher minimal inhibitory concentrations (MICs) of β-Lactamases such as imipenem and meropenem [[#References |[7]]]. Resistance to common β-Lactamases antibiotics is likely due to the expression of most blaB and GOB genes as many of which are broad spectrum MBLs [[#References |[8]]]. Studies on the expression of MBL genes shows that in poor growing conditions and environments with β-Lactamase antibiotics, expression of MBLs increased [[#References |[8]]]. Evidence for induction of Bla genes by other Bla genes, bolA, and ampR genes is also observed although not conclusive [[#References |[8]]].



Revision as of 07:29, 15 December 2018

This student page has not been curated.


Edited by [Luisadrian Bernal-Mena], student of Jennifer Talbot for BI 311 General Microbiology, 2018, Boston University.



This student page has not been curated.

Classification

Higher order taxa

Bacteria (Domain); Bacteroidetes (Phylum); Flavobacteriia (Class); Flavobacteriales (Order); Flavobacteriaceae (Family); Elizabethkingia (Genus) [1]

Species

Elizabethkingia meningoseptica

Description and significance

Elizabethkingia meningoseptica is a rod-shaped, Gram-negative bacterium found ubiquitously in soil and water [2]. The prokaryote is characterized as non-motile, non-fermentative bacterium incapable of producing spores [3],[4]. E. meningoseptica has a symbiotic role with Gnetum gnemon by reducing nitrogen in the rhizoplane of the tree. Recent studies have drawn attention to the pathogenicity of E. meningoseptica (REF). The prokaryote is responsible for several nosocomial outbreaks which put infants and immunocompromised adults at risk. It is resistant to β-lactam medications commonly used to treat Gram-negative bacterial infections [4]. E. meningoseptica’s alarming resistance to common antibiotics is amplified as recent studies show a commensal relationship between the bacterium and the midgut of Anopheles mosquitoes, rendering mosquitoes an efficient vector for transmission [4].

Genome structure

A draft genome of E. meningoseptica was initially sequenced in (year). Initial sequencing provided a total of 10 contigs, with the final count 4,038,467 nucleotides [16]. 36.37% of the nucleotides were G-C base pairs while the remaining were A-T base pairs [16]. 3,571,073 (88.44% total genome) base pairs were coding, responsible for 3,729 total genes, 3,673 of which were protein coding [17]. Many genes were responsible for translation (8.58%), transcription (7.84), cell wall synthesis (8.49%), amino acid transport (8.49%) and ionic transport (7.06%); 46.55% of genes, however, are undefined [5], [6]. Initially thought the same species, Elizabethkingia anophelis ribosomal 16S was 98% identical to that of E. meningoseptica [5]. However, additional findings suggest that due to significant differences in protein coding regions, they are two separate species [5].

Genes of Interest

Gene BFF93_RS16990, a member of the CDC family, was found in E. meningoseptica [6]. Although usually found in pathogenic Gram-positive bacteria, this CDC gene is a major virulence factor of E. meningoseptica [6]. CDC genes generally allow the transport of protein into host cells, many of which transport hemolysin, an enzyme that can potentially kill host erythrocytes [6]. Additionally, this CDC gene was found downstream of hmuY gene which is responsible for iron metabolism; this hints toward erythrocytes as E. meningoseptica’s primary or potentially its only source of iron and nutrients hence its pathogenicity in bloodstreams [6]. Furthermore, this CDC gene encodes for perfringolysin, a cytotoxic and leukostasis toxin that allows the evasion of phagocytic activity of host immune systems [5],[6]. Gene BFF93_RS1398 was also found in E. meningoseptica. Common in pathogenic bacteria, BFF93_RS1398 encodes hemagglutinins, proteins used by many invasive bacteria as adhesive elements onto host cells [5]. Evidence of additional operons involved in curli biosynthesis was also found in clinical strains which not only allowed increase biofilm production, but also increase is cell attachment and aggregation [6].

Metallo-β-Lactamase Genes

Production of Metallo-β-Lactamases (MBLs) was detected in all clinical strains [7]. Up to 13 unique blaB and 17 blaGOB genes were identified, of which, 5 of blaB and 10 of blaGOB were discovered recently and contribute up to 2-4 times higher minimal inhibitory concentrations (MICs) of β-Lactamases such as imipenem and meropenem [7]. Resistance to common β-Lactamases antibiotics is likely due to the expression of most blaB and GOB genes as many of which are broad spectrum MBLs [8]. Studies on the expression of MBL genes shows that in poor growing conditions and environments with β-Lactamase antibiotics, expression of MBLs increased [8]. Evidence for induction of Bla genes by other Bla genes, bolA, and ampR genes is also observed although not conclusive [8].



Cell structure and metabolic processes

E. meningoseptica is a Gram-negative, aerobic chemoorganotroph, rod-shaped with a slight curve, and non-motile [2],[4]. Roughly 0.7 μm in diameter and 24.0 μm in length, E. meningoseptica is longer than the average rod-shaped bacteria [5]. Similar to other Chryseobacterium and Elizabethkingia species, E. meningoseptica has a strictly respiratory, not fermentative, metabolism. It has a high tolerance to NaCl. When cultured its colonies can have a weak yellow pigment or non-pigmented depending on the strain [2]. Although there is not a consensus, it is thought that E. meningoseptica produce small amounts of flexirubin type pigment in presence of light [2]. The major polyamine in its structure is homospermidine [9], and some E. meningoseptica strains also have the ability to produce acid from trehalose, and β-galactosidase [10]. Research also shows that E. meningoseptica have heat- and protease-sensitive adhesins localized on the cell surface. Some E. meningoseptica strains are encapsulated [11], which could explain why some of its strains are hydrophilic, and for its autoaggregation [12]. While it is known that the primary component of its capsule is polysaccharides, it is also theorized that protein adhesion molecules may also be present, making the capsule of E. meningoseptica act as a receptor for lectins on other bacteria [13]. Adherence tests suggest E. meningoseptica has higher than normal ability to adhere and aggregate as well as the ability to form biofilms [14],[15],[16]. Xylene assay shows the presence of a hydrophilic surface which allows strong adherence to both organic and abiotic surfaces [14]. Heat-treatment disrupted surface adhesion which may suggest proteins as an adhesive element rather than hydrophilic interaction [5], [16]. Due to the presence of additional lipopolysaccharide as the outermost layer of its cell wall, E. meningoseptica is able to avoid most broad spectrum antibiotic. Presence of periplasmic space further fostered antibiotic resistance by allowing near-surface storage of anti-antibiotics such as extended-spectrum β-lactamases [6]. E. meningoseptica’s ability to produce at least two different types of b-lactamases, a noninducible extended-spectrum, and a carbapenem-hydrolyzing one [17], is one of the reasons why while some E. meningoseptica isolates are vulnerable to ureidopenicillins, most strains are generally resistant to extended spectrum cephalosporins and carbapenems [2].

Ecology

Work on the ecological role of E. meningoseptica has been limited despite the abundance of the bacteria in soil (REF). Some strains of E. meningoseptica are able to reduce nitrite, a characteristic beneficial for flora and are found in the rhizoplane of the plant species Gnetum gnemon, suggesting a symbiotic relationship between the tree and bacterium [18]. E. meningoseptica is not involved in a symbiotic relationship with other plants, most likely because other highly specialized bacteria outcompete E. meningoseptica [18]. While E. meningoseptica has little interaction with fauna, recent studies show several species of the genus Elizabethkingia, including E. meningoseptica, have a commensal role in the midgut of Anopheles mosquitoes [19]. E. meningoseptica comprise a large portion of the microbial community in the mosquitoes’ midgut. However further research is necessary to shed light on the specific physiological functions that E. meningoseptica has on the mosquitoes at different developmental stages.


Pathology

The optimal growth conditions for E. meningoseptica, which includes cool, moist environments or still water at 21°C, can be found in various hospital environments [20]. E. meningosceptica can cause severe diseases in the human population [4]. In recent years, multiple outbreaks have been reported in hospitals that have poor sanitary procedures [4]. E. meningosceptica poses a huge risk to immunocompromised patients. These outbreaks can be caused primarily by exposure to contaminated water or medical devices. It was also found to be resistant against chlorinated water and grow in hospital sinks [21]. A leading infection that is of concern and commonly caused by E. meningosceptica is bacteremia [4],[8],[22]. Bacteremia is the presence of bacteria in the blood and if not discovered or treated in time may be lethal to the victim. E. meningosceptica has also been found to be associated with outbreaks of neonatal meningitis, endocarditis, and pneumonia [4]. E. meningoseptica, and even Chryseobacterium and Elizabethkingia species, are separated from other Gram-negative bacteria due to their increased resistance to most antimicrobial agents and general susceptibility patterns [2]. Isolates from clinical settings also showed a significantly better ability to form biofilms and accumulate in hosts compared to wild types which may signify a gene shift towards mutants with higher virulence factors [5]. E. meningosceptica contain three bla genes that code for the extended spectrum serine-B-lactamase, BlaBm, and GOB, which play a unified effort into the resistance of specific antibiotics [8]. This allows for E. meningosceptica to break down the antibiotics given to it and pose as a major threat to the environment it is currently present in [8]. In addition to its resistance to antimicrobial agents, E. meningoseptica is also resistant to chlorine and many other disinfectants making it much harder to fight against [23]. However, E. meningosceptica is susceptible to antibiotics used against Gram-positive bacteria though. Two antibiotics that have shown promise are Vancomycin and Rifampin [28]. Vancomycin is effective when combating infantile meningitis but results showing its ineffectiveness have also been recorded with high MIC values [25],[26],[27]. Hospitals have also successfully developed ways to stop outbreaks via pre-emptive contact isolation, systemic investigations to identify the source and through thorough cleaning of the equipment [22].


Current Research

While the genetics of E. meningoseptica and Elizabethkingia are still mostly uninvestigated, systems like gene transfer, selectable marker and suicide vector, that were developed to genetically manipulate Flavobacterium johnsoniae, have been successfully used on E. meningoseptica [28],[29]. The ability to manipulate E. meningoseptica genetically, as well as its high productivity, brief multiplication time, and inexpensive substrates, researchers consider E. meningoseptica as a bacterium with possible applications in the medical and pharmaceutical industry [30]. A recent study by Liu et al. (2018) showed that site-directed mutagenesis in E. meningoseptica can lead to increasing menaquinone (vitamin K2), which has shown to minimizing bone fractures and bone loss [31],[32], in addition to alleviating Parkinson’s disease and restoring mitochondrial dysfunction [33],[34],[35]. Other research conducted on E. meningoseptica and its surrounding factors are focused on understanding hospital acquired infections and the factors surrounding it [22]. Research done on the infections caused by E. meningoseptica have also led to a better understanding of infectious diseases and ways to better combat against multi-drug resistance [36].

References

[1] [“Taxonomy Browser.” National Center for Biotechnology Information, U.S. National Library of Medicine, www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=238&lvl=3&keep=1&srchmode=1&unlock&lin=s&log_op=lineage_toggle [Webpage]. (Accessed: Oct 21, 2018)]

[2] [Bernardet J-F, Hugo C, Bruun B: The genera Chryseobacterium and Elizabethkingia. In The Prokaryotes. Volume 7.. 3 edition. Edited by: Dworkin M, Falkow S, Rosenberg E, Schleifer K-H, Stackebrandt E. New York: Springer; 2006:638-676.]

[3] [Kim KK, Kim Mk, Lim JH, Park HY, Lee S. 2005. Transfer of Chryseobacterium meningosepticum and Chryseobacterium miricola to Elizabethkingia gen. nov. as Elizabethkingia meningoseptica comb. nov. and Elizabethkingia miricola comb. Intl. J. Sys. Evo. Microb. 55: 1287-1293]

[4] [Shinha T, Ahuja R, 2015. Bacteremia due to Elizabethkingia meningoseptica El Sevier. 2 (1): 13-15.]

[5] [Chen S, Seohnlen M, Walker ED. 2016. Genome Sequence of Elizabethkingia meningoseptica EM1, Isolated from a Patient with a Bloodstream Infection. Genome Announcements, 4 (5): e01137-16.]

[6] [Chen S, Soehnlen M, Downes FP, Walker ED. Insights from the draft genome into the pathogenicity of a clinical isolate of Elizabethkingia meningosepticaEm3. Standards in Genomic Sciences. 2017;12:56. doi:10.1186/s40793-017-0269-8.]

[7] [Yum JH, Lee EY, Hur SH. Jeong SH, Lee H, Yong D, Chong Y, Lee EW, N P. Lee K. 2010. Genetic Diversity of Chromosomal Metallo-β-Lactamase Genes in Clinical Isolates of Elizabethkingia meningoseptica from Korea. Journal of Microbiology. 2010, 48(3), 358-364.]

[8] [Gonzalez LJ and Vila AJ. Carbapenem Resistance in Elizabethkingia meningoseptica is Mediated by Metallo-β-Lactamase BlaB. American Society for Microbiology Journals. 2012, 56 (4), 1686-1692.]

[9][Hamana, K., and S. Matsuzaki. 1990. Occurrence of homospermidine as a major polyamine in the authentic genus Flavobacterium. Can. J. Microbiol. 36:228–231.] [10][Bülow, P. 1964. The ONPG test in diagnostic bacteriology. Acta Pathol. Microbiol. Scand. 60:376–402]

[11][Holmes, B., R. J. Owen, and T. A. McMeekin. 1984. Genus Flavobacterium Bergey, Harrison, Breed, Hammer and Huntoon 1923, 97AL. In: N. R. Krieg and J. G. Holt (Eds.) Bergey’s Manual of Systematic Bacteriology. Williams & Wilkins. Baltimore, MD. 1:353–361.]

[12][Jacobs A, Chenia HY. Biofilm formation and adherence characteristics of an Elizabethkingia meningoseptica isolate from Oreochromis mossambicus. Ann Clin Microbiol Antimicrob. 2011;10:16.]

[13][Ofek I, Doyle RJ: Bacterial adhesion to animal cells and tissues Washington, D.C.: ASM Press; 1994.]

[14][Matyi SA, Hoyt PR, Hosoyama A, Yamazoe A, Fujita N, Gustafson JE. Draft genome sequences of Elizabethkingia meningoseptica. Genome Announc. 2013;1(4):e00444–e00413. doi: 10.1128/genomeA.00444-13.]

[15][Lin P-Y, Chen H-L, Huang C-T, Su L-H, Chiu C-H: Biofilm production, use of indwelling catheters and inappropriate antimicrobial therapy as predictors of fatality in Chryseobacterium meningosepticum bacteraemia. Int J Antimicrob Agent 2010, 36:436-440.]

[16][Vivas J, Padilla D, Real F, Bravo J, Grasso V, Acosta F: Influence of environmental conditions on biofilm formation by Hafnia alvei strains. Vet Microbiol 2008, 129:150-155.]

[17][Bellais, S., L. Poirel, T. Naas, D. Girlich, and P. Nordmann. 2000. Genetic-biochemical analysis and distribution of the Ambler Class A beta-lactamase CME-2, responsible for extended-spectrum cephalosporin resistance in Chryseobacterium (Flavobacterium) meningosepticum. Antimicrob. Agents Chemother. 44:1–9.]

[18][Oh YM, Kim M, Lee-Cruz L, LaiHoe A, Ainuddin N, Rahim RA, Shurkor N, Adams JM, 2012. Distinctive Bacterial Communities in the Rhizoplane of Four Tropical Tree Species. Microb Ecol 64 (18): 1018-1027.]

[19][Chen S., Bagdasarian M., Walker E.D. 2015. Elizabethkingia anophelis: Molecular Manipulation and Interactions with Mosquito Hosts. Am. Soc. Microbio. 2015; 81 (6) 2233-2243.]

[20][Bloch KC, Nadarajah R, Jacobs R: Chryseobacterium meningosepticum: an emerging pathogen among immunocompromised adults: report of 6 cases and literature review. Med (Baltimore) 1997, 76:30-41.]

[21][Rathnamani MS, Rao R, 2013. Elizabethkingia meningoseptica: Emerging nosocomial pathogen in bedside hemodialysis patients. Indian J Crit Care Med. 17(5): 304-307.]

[22][Jean S., Lee W., Chen F., Ou T., Hsueh P, 2014. Elizabethkingia meningoseptica: an important emerging pathogen causing healthcare-associated infections. Journal of Hospital Infections. 86 (4): 244-249.]

[23][Green, S. L., D. M. Bouley, R. J. Tolwani, K. S. Waggie, B. D. Lifland, G. M. Otto, and J. E. Ferrell. 1999. Identification and management of an outbreak of Flavobacterium meningosepticum infection in a colony of South African clawed frogs (Xenopus laevis). J. Am. Vet. Med. Assoc. 214:1833–1838.]

[24][Di Pentima M.C., Mason E.O., Jr., Kaplan S.L. In vitro antibiotic synergy against Flavobacterium meningosepticum: implications for therapeutic options. Clin Infect Dis. 1998; 26(5):1169–1176.]

[25][Hirsh B.E., Wong B., Kiehn T.E., Gee T., Armstrong D. Flavobacterium meningosepticumbacteremia in an adult with acute leukemia. Use of rifampin to clear persistent infection. Diagn Microbiol Infect Dis. 1986;4(1):65–69.]

[26][Fraser S.L., Jorgensen J.H. Reappraisal of the antimicrobial susceptibilities of Chryseobacterium and Flavobacterium species and methods for reliable susceptibility testing. Antimicrob Agents Chemother. 1997;41(12):2738–2741.]

[27][George R.M., Cochran C.P., Wheeler W.E. Epidemic meningitis of the newborn caused by flavobacteria. II. Clinical manifestations and treatment. Am J Dis Child. 1961;101:296–304.]

[28][Hawley H.B., Gump D.W. Vancomycin therapy of bacterial meningitis. Am J Dis Child. 1973;126(2):261–264.]

[29][McBride, M. J., and S. A. Baker. 1996. Development of techniques to genetically manipulate members of the genera Cytophaga, Flavobacterium, Flexibacter, and Sporocytophaga. Appl. Environ. Microbiol. 62:3017–3022.]

[30][Liu, Y., Yang, Z., Xue, Z., Qian, S., Wang, Z., Hu, et al. . (2018). Influence of site-directed mutagenesis of UbiA, overexpression of dxr , menA and ubiE , and supplementation with precursors on menaquinone production in Elizabethkingia meningoseptica. Process Biochemistry,68, 64-72.]

[31][H.J. Boukaert, A.H. Said, Fracture healing by vitamin K, Nature 19 (1960) 849.]

[32][Y. Ishida, Vitamin K2, Clin. Calcium 18 (2008) 1476–1482.]

[33][M. Vos, G. Esposito, J.N. Edirisinghe, S. Vilain, D.M. Haddad, J.R. Slabbaert, S.V. Meensel, O. Schaap, B.D. Strooper, R. Meganathan, V.A. Morais, P. Verstreken, Vitamin K2 is a mitochondrial electron carrier that rescues pink1 deficiency, Science 336 (2012) 1306–1310.]

[34][M. Vos, G. Esposito, J.N. Edirisinghe, S. Vilain, D.M. Haddad, J.R. Slabbaert, S.V. Meensel, O. Schaap, B.D. Strooper, R. Meganathan, V.A. Morais, P. Verstreken, Vitamin K2 is a mitochondrial electron carrier that rescues pink1 deficiency, Science 336 (2012) 1306–1310.]

[35][K. Nakagawa, Y. Hirota, N. Sawada, N. Yuge, M. Watanabe, Y. Uchino, N. Okuda, Y. Shimomura, Y. Suhara, T. Okano, Identification of UBIAD1 as a novel human menaquinone-4 biosynthetic enzyme, Nature 468 (2010) 117–122.]

[36][Rastogi N., MathurP., Bindra A., Goyal K., Sokhal N., Kumar S., Sagar S., Aggarwal R., Soni K.D., Tandon V. Infections due to Elizabethkingia meningoseptica in critically injured trauma patients: a seven-year study. Journal of Hospital Infection. 92: 30-32.]




Edited by [Jennifer Talbot], student of Jennifer Talbot for BI 311 General Microbiology, 2016, Boston University.