Elizabethkingia meningoseptica
Edited by Luisadrian Bernal-Mena, Jaime Andrés Rodríguez, Yi Bo Wang and Ekin Kurak, students of Jennifer Talbot for BI 311 General Microbiology, 2018, Boston University.
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
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Edited by Luisadrian Bernal-Mena, Jaime Andrés Rodríguez, Yi Bo Wang and Ekin Kurak, students of Jennifer Talbot for BI 311 General Microbiology, 2018, Boston University.
