Biochemical characterization of the novel α-1, 3-galactosyltransferase WclR from Escherichia coli O3

Chen, Chao; Liu, Bin; Xu, Yongchang; Utkina, Natalia; Zhou, Dawei; Данилов, Л. Л.; Торгов, В. И.; Veselovsky, V. V.; Feng, Lu

doi:10.1016/j.carres.2016.04.012

Cited by 21 publications

(8 citation statements)

References 27 publications

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“…Another important variable may be the exposure to different types and levels of microorganisms of the healthy microbiota. Several bacterial pathogens able to synthetize α1,3-Gal such as Escherichia coli (34), Streptococcus pneumonia (33) Salmonella (16) or parasites may also contribute to immunization in the childhood or adulthood in specific pathological contexts. Moreover, inflammatory bowel diseases and gastrointestinal infections are particularly associated with adherent-invasive Escherichia coli (37)(38)(39).…”

Section: Discussionmentioning

confidence: 99%

Distribution of Bacterial α1,3-Galactosyltransferase Genes in the Human Gut Microbiome

et al. 2020

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Because of a loss-of-function mutation in the GGTA1 gene, humans are unable to synthetize α1,3-Galactose (Gal) decorated glycans and develop high levels of circulating anti-α1,3-Galactose antibodies (anti-Gal Abs). Anti-Gal Abs have been identified as a major obstacle of organ xenotransplantation and play a role in several host-pathogen relationships including potential susceptibility to infection. Anti-Gal Abs are supposed to stem from immunization against the gut microbiota, an assumption derived from the observation that some pathogens display α1,3-Gal and that antibiotic treatment decreases the level of anti-Gal. However, there is little information to date concerning the microorganisms producing α1,3-Gal in the human gut microbiome. Here, available α1,3-Galactosyltransferase (GT) gene sequences from gut bacteria were selectively quantified for the first time in the gut microbiome shotgun sequences of 163 adult individuals from three published population-based metagenomics analyses. We showed that most of the gut microbiome of adult individuals contained a small set of bacteria bearing α1,3-GT genes. These bacteria belong mainly to the Enterobacteriaceae family, including Escherichia coli, but also to Pasteurellaceae genera, Haemophilus influenza and Lactobacillus species. α1,3-Gal antigens and α1,3-GT activity were detected in healthy stools of individuals exhibiting α1,3-GT bacterial gene sequences in their shotgun data.

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Section: Discussionmentioning

confidence: 99%

Distribution of Bacterial α1,3-Galactosyltransferase Genes in the Human Gut Microbiome

et al. 2020

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“…The synthesis of the glycan Galα1-3Galβ1-4GlcNAc-R (α-Gal) by the enzyme α-1,3-galactosyltransferase occurs in bacteria [10][11][12][13], fungi [14][15][16], and noncatarrhine mammals [17], but prokaryotic and eukaryotic α-1,3-galactosyltransferase genes and proteins share little structural homology [18][19][20]. Humans, old world monkeys and apes evolved with the inability to synthesize α-Gal, which resulted in the capacity to produce anti-α-Gal IgM/IgG antibodies with a protective activity against pathogenic viruses (e.g., HIV), bacteria (e.g., Mycobacterium) and parasites (e.g., Plasmodium), containing this modification on membrane proteins [21][22][23].…”

Section: Introductionmentioning

confidence: 99%

“…The natural IgM/IgG antibodies against α-Gal are produced in response to gut microbiota bacteria having this modification [21,24]. Several bacteria of the family Enterobacteriaceae such as Klebsiella pneumonia [10], Escherichia coli [11,12] and Salmonella spp. [13,24] are known to express α1,3-galactosyltransferase genes, and to synthetize α-Gal, in the human gut microbiome [24].…”

Section: Introductionmentioning

confidence: 99%

Anti-Tick Microbiota Vaccine Impacts Ixodes ricinus Performance during Feeding

Mateos-Hernández

Obregón

Mayé³

et al. 2020

Vaccines

118

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The tick microbiota is a highly complex ensemble of interacting microorganisms. Keystone taxa, with a central role in the microbial networks, support the stability and fitness of the microbial communities. The keystoneness of taxa in the tick microbiota can be inferred from microbial co-occurrence networks. Microbes with high centrality indexes are highly connected with other taxa of the microbiota and are expected to provide important resources to the microbial community and/or the tick. We reasoned that disturbance of vector microbiota by removal of ubiquitous and abundant keystone bacteria may disrupt the tick-microbiota homeostasis causing harm to the tick host. These observations and reasoning prompted us to test the hypothesis that antibodies targeting keystone bacteria may harm the ticks during feeding on immunized hosts. To this aim, in silico analyses were conducted to identify keystone bacteria in the microbiota of Ixodes nymphs. The family Enterobacteriaceae was among the top keystone taxa identified in Ixodes microbiota. Immunization of α-1,3-galactosyltransferase-deficient-C57BL/6 (α1,3GT KO) mice with a live vaccine containing the Enterobacteriaceae bacterium Escherichia coli strain BL21 revealed that the production of anti-E. coli and anti-α-Gal IgM and IgG was associated with high mortality of I. ricinus nymphs during feeding. However, this effect was absent in two different strains of wild type mice, BALB/c and C57BL/6. This result concurred with a wide distribution of α-1,3-galactosyltransferase genes, and possibly α-Gal, in Enterobacteriaceae and other bacteria of tick microbiota. Interestingly, the weight of I. ricinus nymphs that fed on E. coli-immunized C57BL/6 was significantly higher than the weight of ticks that fed on C57BL/6 immunized with a mock vaccine. Our results suggest that anti-tick microbiota vaccines are a promising tool for the experimental manipulation of vector microbiota, and potentially the control of ticks and tick-borne pathogens.

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“…Surprisingly, recent results revealed that double-KO pigs for the genes ggta1 and a3galT 2 have α-Gal-residual activity 13 . Fungi and bacteria also express α1-3 galt genes encoding for enzymes that synthetize α-Gal, but prokaryotic and eukaryotic α1-3 GALT proteins share little structural homology 1 , 14 – 16 . These results suggested that (i) α1-3 GALTs activity is redundant in animal tissues, (ii) all the enzymes responsible for α-Gal synthesis in animals have not been discovered, and (iii) α1-3 GALT enzymes have evolved independently in prokaryotic and eukaryotic organisms.…”

Section: Introductionmentioning

confidence: 99%

Tick galactosyltransferases are involved in α-Gal synthesis and play a role during Anaplasma phagocytophilum infection and Ixodes scapularis tick vector development

Cabezas-Cruz

Espinosa

Alberdi

et al. 2018

Sci Rep

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The carbohydrate Galα1-3Galβ1-(3)4GlcNAc-R (α-Gal) is produced in all mammals except for humans, apes and old world monkeys that lost the ability to synthetize this carbohydrate. Therefore, humans can produce high antibody titers against α-Gal. Anti-α-Gal IgE antibodies have been associated with tick-induced allergy (i.e. α-Gal syndrome) and anti-α-Gal IgG/IgM antibodies may be involved in protection against malaria, leishmaniasis and Chagas disease. The α-Gal on tick salivary proteins plays an important role in the etiology of the α-Gal syndrome. However, whether ticks are able to produce endogenous α-Gal remains currently unknown. In this study, the Ixodes scapularis genome was searched for galactosyltransferases and three genes were identified as potentially involved in the synthesis of α-Gal. Heterologous gene expression in α-Gal-negative cells and gene knockdown in ticks confirmed that these genes were involved in α-Gal synthesis and are essential for tick feeding. Furthermore, these genes were shown to play an important role in tick-pathogen interactions. Results suggested that tick cells increased α-Gal levels in response to Anaplasma phagocytophilum infection to control bacterial infection. These results provided the molecular basis of endogenous α-Gal production in ticks and suggested that tick galactosyltransferases are involved in vector development, tick-pathogen interactions and possibly the etiology of α-Gal syndrome in humans.

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Biochemical characterization of the novel α-1, 3-galactosyltransferase WclR from Escherichia coli O3

Cited by 21 publications

References 27 publications

Distribution of Bacterial α1,3-Galactosyltransferase Genes in the Human Gut Microbiome

Distribution of Bacterial α1,3-Galactosyltransferase Genes in the Human Gut Microbiome

Anti-Tick Microbiota Vaccine Impacts Ixodes ricinus Performance during Feeding

Tick galactosyltransferases are involved in α-Gal synthesis and play a role during Anaplasma phagocytophilum infection and Ixodes scapularis tick vector development

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