Elizabethkingia anophelis
Classification
Higher order taxa
Bacteria; Bacteroidete; Flavobacteria; Flavobacteriales; Flavobacteriaceae
Species
Elizabethkingia anophelis
Description and significance
Elizabethkingia anophelis is a bacteria species in the family Flavobacteriaceae. The bacterium is a slightly yellow-pigmented, non-motile, non-spore-forming, gram-negative, rod-shaped cell [1] [2]. Elizabethkingia anophelis has two growth optima at 30-31 °C and 37 °C [1]. It is a dominant resident in the mosquito gut of the malaria vector mosquito Anopheles gambiae and also a human pathogen [3]. Recently (2013) E. anopheles was reported as a human pathogen in Central Africa and an outbreak was also seen in an intensive care unit in Singapore; in both clinical cases multidrug resistance was reported [3].
Genome structure
Elizabethkingia anophelis has a circular genome of 4,369,828 base pairs and 4,141 predicted coding sequences [4]. 16S rRNA gene sequence analysis revealed that the isolate (Elizabethkingia anopheles) showed 98.6 % sequence similarity to that of Elizabethkingia meningoseptica ATCC 13253(T) and 98.2 % similarity to that of Elizabethkingia miricola GTC 862(T) [3]. DNA-DNA hybridization experiments with E. meningoseptica CCUG 214(T) ( = ATCC 13253(T)) and E. miricola KCTC 12492(T) ( = GTC 862(T)) gave relatedness values of 34.5 % (reciprocal 41.5 %) and 35.0 % (reciprocal 25.7 %), respectively [1]. DNA-DNA hybridization results and some differentiating biochemical properties indicate that strain R26(T) represents a novel species, for which the name Elizabethkingia anophelis sp. nov. is proposed [3]. The type strain is R26(T) ( = CCUG 60038(T) = CCM 7804(T)) [1]. The draft genomes were annotated using the NCBI Prokaryotic Genome Automatic Annotation Pipeline (http://www.ncbi.nlm.nih.gov/genome/annotation_prok/) [5], which predicted 3,687 protein-coding sequences (CDS) and 44 RNA genes in R26(T) and 3,648 CDS and 38 RNA genes in Ag1. Strikingly, 112 protein features were identified in the category “resistance to antibiotics and toxic compounds” [3]. This included drug efflux/transport (36 features); resistance to β-lactam antibiotics, fluoroquinolones, and heavy metals (28, 4 and 25 features, respectively); and 19 additional features involved in resistance to a diverse set of antibiotics [3]. The large genetic capacity against various antibiotics is consistent with the observation that E. anophelis has natural antibiotic resistance to several antibiotics [3].
Cell structure and metabolism
E. anophelis is a slightly yellow, non-motile, non-spore-forming, Gram negative rod [2]. The bacterium has two growth optima at 30-31 °C and 37 °C [1]. The bacterium utilizes complex carbohydrates (glycans) in its metabolism with starch-utilization systems (Sus) including proteins SusD (glycan-binding protein), SusC (Ton-B dependent transporter), SusE/SusF (carbohydrate-binding proteins without enzyme activity), SusA, SusB, SusG (enzymes for polysaccharide deconstruction) and SusR (an inner membrane-associated sensor-regulator system for transcriptional activation of Sus genes) [2]. The major fatty acids of E. anophelis, strain R26(T) were iso-C(15 : 0), iso-C(17 : 0) 3-OH and summed feature 4 (iso-C(15 : 0) 2-OH and/or C(16 : 1)ω7c/t). Strain R26(T) contained only menaquinone MK-6 and showed a complex polar lipid profile consisting of diphosphatidylglycerol, phosphatidylinositol, an unknown phospholipid and unknown polar lipids and glycolipids [1]. The bacterium produces several hemolysins that may participate in the digestion of erythrocytes in the mosquito gut [2]. Numerous TonB-dependent transporters (TBDTs) with various substrate specificities help the bacterium to utilize polymers [2]. E. anophelis has well-developed systems for scavenging iron and stress response [4]. The bacterial TBDTs are specialized elaborate machinery for active uptake of rare but essential nutrients and other substrates, such as iron complexes, vitamin B12, nickel, carbohydrates and colicin [2]. To energize the transport process, TBDTs interact with the TonB complex, a cytoplasmic transmembrane assembly of the proteins ExbB and ExbD, which couples with the TonB in periplasm [2]. The cell also produces efflux pumps and β-lactamases that give the bacterium broad antibiotic resistence [2]. RNA-sequencing-based transcriptome profiling indicates that expressions of genes involved in synthesis of a yersinibactin-like iron siderophore and heme utilization are highly induced as a protective mechanism toward oxidative stress caused by hydrogen peroxide stress [4]. E. anophelis produces OxyR regulon and antioxidants that may provide defense against the oxidative stress that is associated with blood digestion in mosquitoes [2]. One study showed that hemoglobin facilitates the growth, hydrogen peroxide tolerance, cell attachment, and biofilm formation of E. anophelis and that siderophore production and heme uptake pathways might play essential roles in stress response and virulence [4].
Ecology
Elizabethkingia anophelis is a dominant bacterial species in the gut ecosystem of the malaria vector mosquito Anopheles gambiae [3]. Like some Bacteroidetes, E. anophelis possesses polysaccharide utilization loci (PUL), which suggests the genetic capability to utilize various plant polysaccharides [3]. This implies an intriguing ecological connection with the nectar and plant sap feeding behavior of mosquitoes in nature [3]. The predominance of E. anophelis in the sugar fed gut of mosquitos and the possession of numerous Sus-like loci and GHs suggest that the bacterium may be capable of utilizing plant cellulose in the diet and could potentially be of benefit for the mosquito carbohydrate metabolism [2] [6]. The interactions among antibiotic-producing and resistant bacteria may be one of the determinants that shape and stabilize the community structure in the mosquito gut [2]. The bacterium also display hemolytic activity and encode several hemolysins that may participate in the digestion of erythrocytes in the mosquito gut [2]. At the same time, the OxyR regulon and antioxidant genes could provide defense against the oxidative stress that is associated with blood digestion [2]. The genome annotation and comparative genomic analysis revealed functional characteristics associated with the symbiotic relationship with the mosquito host [2].
Pathology
Recently (2013), E. anophelis was reported as a human pathogen in Central Africa in a clinical case of meningitis and an outbreak was also seen in an intensive care unit in Singapore [3][2]. In both clinical cases multidrug resistance was reported and the isolates were resistant against a wide array of antibiotics [3][2]. One study [6] highlights that E. anophelis is an emerging bacterial pathogen for hospital environments. It has been associated with neonatal meningitis and nosocomial outbreaks; however, its transmission route remains unknown [7]. Rapid genome sequencing and comparative genomics was used to investigate 3 cases of E. anophelis sepsis involving 2 neonates who had meningitis and 1 neonate’s mother who had chorioamnionitis in Hong Kong providing evidence for perinatal vertical transmission from a mother to her neonate; the 2 isolates from these patients, HKU37 and HKU38, shared essentially identical genome sequences [7]. In contrast, the strain from another neonate (HKU36) was genetically divergent, showing only 78.6% genome sequence identity to HKU37 and HKU38, thus excluding a clonal outbreak [7]. Comparison to genomes from mosquito strains revealed potential metabolic adaptations in E. anophelis under different environments [7]. Maternal infection, not mosquitoes, is most likely the source of neonatal E. anophelis infections [7]. The pathogenic and multiresistant nature of the bacteria prompts investigations of the vector potential of mosquitoes for E. anophelis transmission to humans [3]. The antibiotic resistance might have consequences for future work with E. anophelis [2]. These case reports raised a concern regarding whether or not mosquitoes can pass E. anophelis and E. meningoseptica to humans in clinical situations and when handling mosquitoes in research [2]. Further investigation is required to evaluate these potential risks [2].
References
[1] Kampfer, P., H. Mathews, S.P. Glaesar, K. Martin, N. Lodders, and I. Faye (2011) Elizabethkingia anophelis sp. nov., isolated from the midgut of the mosquito Anopheles gambiae, International Journal of Systematic and Evolutionary Microbiology. 61: 11, 2670-5; doi/10.1099/ijs.0.026393-0.
[2] Kukutla, P., B.G. Lindberg, D. Pei, M. Rayl, W. Yu, and M. Steritz (2014) Insights from the Genome Annotation of Elizabethkingia anophelis from the Malaria Vector Anopheles gambiae, PLoS ONE 9: 5, e97715; doi/10.1371/journal.pone.0097715.
[3] Kukutla, P., Bo G. Lindburg, M. Rayl, W. Yu, M. Steritz, I. Faye, and J. Xu (2013) Draft Genome Sequences of Elizabethkingia anophelis Strains R26T and Ag1 from the Midgut of the Malaria Mosquito Anopheles gambiae, Genome Announc. 1: 6, e01030-13; doi/10.1128/genomeA.0130-13.
[4] Li, Y., Y. Liu, S.C. Chew, M. Tay, M.M.S. Salido, J. Teo, F.M. Lauro, M. Givskov, L. Yang (2015) Complete Genome Sequence and Transcriptomic Analysis of the Novel Pathogen Elizabethkingia anophelis in Response to Oxidative Stress, Genome Biology and Evolution. 7: 6, 1676-1685; doi/10.1093/gbe/evv101.
[5] http://www.ncbi.nlm.nih.gov/genome/annotation_prok/, retrieved October 5th, 2015.
[6] Teo, J., S.Y. Tan, Y. Liu, M. Tay, Y. Ding, Y. Li, S. Kjelleberg, M. Givskov, R.T.P. Lin, and L. Yang (2014) Comparative Genomic Analysis of Malaria Mosquito Vector-Associated Novel, Genome Biology and Evolution. 6: 5, 1158-1165; doi/10.1093/gbe/evu094.
[7] Lau, S.K.P., A.K.L. Wu, J.L.L. Teng, H. Tse, S.O.T. Curreem, S.K.W. Tsui, Y. Huang, J.H.K. Chen, R.A. Lee, K. Yuen, and P.C.Y. Woo (2015) Evidence for Elizabethkingia anopheles Transmission from Mother to Infant, Hong Kong. 21: 2, 1080-6059; doi/10.3201/eid2102.140623.
Page created by Peter J. Richard with Dr. Lisa R. Moore, University of Southern Maine, Department of Biological Sciences, http://www.usm.maine.edu/bio
