Identification of Novel α1,3-Galactosyltransferase and Elimination of α-Galactose-containing Glycans by Disruption of Multiple α-Galactosyltransferase Genes in Schizosaccharomyces pombe

Ohashi, Takao; Fujiyama, Kazuhito; Takegawa, Kaoru

doi:10.1074/jbc.m112.347351

Cited by 17 publications

(6 citation statements)

References 51 publications

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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%

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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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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“…In a previous study, the molecular weight of N-linked oligosaccharide in a gmh1 deletion mutant was almost the same as in the wild-type, whereas that in Δ gmh2 and Δ gmh6 mutants was reduced, and the O-linked oligosaccharide profile in Δ gmh2 and Δ gmh6 mutants was also different from the wild-type (47). In addition, otg1 did not influence the formation of oligosaccharide (48). Glycosylation may be influenced in the quadruple-deletion strain because gmh2 and gmh6 were deleted.…”

Section: Discussionmentioning

confidence: 90%

Characterization of genome-reduced fission yeast strains

Sasaki

Kumagai

Takegawa

et al. 2013

Nucleic Acids Research

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The Schizosaccharomyces pombe genome is one of the smallest among the free-living eukaryotes. We further reduced the S. pombe gene number by large-scale gene deletion to identify a minimal gene set required for growth under laboratory conditions. The genome-reduced strain has four deletion regions: 168.4 kb in the left arm of chromosome I, 155.4 kb in the right arm of chromosome I, 211.7 kb in the left arm of chromosome II and 121.6 kb in the right arm of chromosome II. The deletions corresponded to a loss of 223 genes of the original ∼5100. The quadruple-deletion strain, with a total deletion size of 657.3 kb, showed a decreased ability to uptake glucose and some amino acids in comparison with the parental strain. The strain also showed increased gene expression of the mating pheromone M-factor precursor and the nicotinamide adenine dinucleotide phosphate -specific glutamate dehydrogenase. There was also a 2.7-fold increase in the concentration of cellular adenosine triphosphate, and levels of the heterologous proteins, enhanced green fluorescent protein and secreted human growth hormone were increased by 1.7- and 1.8-fold, respectively. The transcriptome data from this study have been submitted to the Gene Expression Omnibus (GEO: http://www.ncbi.nlm.nih.gov/geo/) under the accession number GSE38620 (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?token=vjkxjewuywgcovc&acc=GSE38620).

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“…Interestingly, Exophiala oligosperma may contain complex α-galactose-containing glycans in the CW, due to expansion of α-1,2-galactosyltransferases from GT34 family. Such α-galactose-containing glycans are present on the cell surface of Schizosaccharomyces pombe [ 88 ]. Chaetothyriales possess a unique domain architecture of β-glucosidases (GH3) with terminal Pir repeats possibly linking the protein to the CW.…”

Section: Resultsmentioning

confidence: 99%

Diversity of Cell Wall Related Proteins in Human Pathogenic Fungi

Muszewska

Piłsyk

Perlińska-Lenart

et al. 2017

JoF

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Abstract:The cell wall is one of the major keys to fungal identity. Fungi use their cell wall to sense the environment, and localize nutrients and competing microorganism. Pathogenic species additionally modify their cell walls to hide from a host's immune system. With the growing number of fungal infections and alarming shortage of available drugs, we are in need of new approaches to fight pathogens. The cell wall seems to be a natural target, since animal host cells are devoid of it. The current knowledge about fungal cell wall components is often limited, and there is huge diversity both in structure and composition between species. In order to compare the distribution of diverse proteins involved in cell wall biosynthesis and maintenance, we performed sequence homology searches against 24 fungal proteomes from distinct taxonomic groups, all reported as human pathogens. This approach led to identification of 4014 cell wall proteins (CWPs), and enabled us to speculate about cell wall composition in recently sequenced pathogenic fungi with limited experimental information. We found large expansions of several CWP families, in particular taxa, and a number of new CWPs possibly involved in evading host immune recognition. Here, we present a comprehensive evolutionary history of fungal CWP families in the context of the fungal tree of life.

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Identification of Novel α1,3-Galactosyltransferase and Elimination of α-Galactose-containing Glycans by Disruption of Multiple α-Galactosyltransferase Genes in Schizosaccharomyces pombe

Abstract: Background:We searched for unidentified ␣1,3-galactosyltransferases in Schizosaccharomyces pombe and identified three novel genes (otg1 ϩ -otg3 ϩ ).

Cited by 17 publications

References 51 publications

Anti-Tick Microbiota Vaccine Impacts Ixodes ricinus Performance during Feeding

Anti-Tick Microbiota Vaccine Impacts Ixodes ricinus Performance during Feeding

Characterization of genome-reduced fission yeast strains

Diversity of Cell Wall Related Proteins in Human Pathogenic Fungi

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