A toxin hunter in the microworld of bacteria: a project on novel inhibitors against bacterial AB5 toxins

[要旨] 病原性細菌が産生する蛋白性のAB5型トキシンは1個のAサブユニットと5個のBサブユニットから構成される外毒素である。両サブユニットはそれぞれ特徴的な役割を持ち，互いに巧妙に機能分担をして一つのトキシンを形成している。Aサブユニットは主に毒性に直接関与する特異的な酵素活性を有する。一方，Bサブユニットは標的細胞のレセプターに対する結合能を有し，AB5型トキシンを標的細胞に吸着させる。ここでは毒性が全く異なるAB5型トキシンとして，コレラ菌が産生するコレラトキシン（CT），腸管出血性大腸菌が産生する志賀様トキシン（Stx），及び志賀トキシン産生大腸菌が産生するサブチラーゼサイトトキシン（SubAB）の3種類に関して，その作用メカニズムに着目した毒性を抑制する阻害因子の探索などの研究を紹介する。これらの3種類のAB5型トキシンに着目した理由は，それぞれのトキシンを産生する病原菌による感染症が世界的に流行し，社会問題となっているからである。つまり，コレラ菌は依然として発展途上国で大きな問題であり，腸管出血性大腸菌のO157:H7による集団食中毒は我国でも依然として多い。さらに21世紀になり，血清型がO157:H7以外の腸管出血性大腸菌による集団食中毒が世界的に急増しているためである。いずれも抗生物質を使用した後の残留トキシンによる病態悪化が指摘されており，トキシンを効率よく無毒化する事が急務である。[SUMMARY] Bacterial AB5 toxins are proteins, produced by pathogenic bacteria including of Vibrio cholerae, Shigella dysenteriae, and enterohaemorrhagic Escherichia coli, which are usually released into the extracellular medium and cause disease by killing or altering the metabolism of target eukaryotic cells. The toxins are usually composed of one A subunit（a toxic domain） and five B subunits（a receptor-binding domain）. This article overviews the characteristics and mode of actions of AB5 toxins including cholera toxin, Shiga-like toxin, and subtilase cytotoxin, and highlights a project on the novel inhibitors against these bacterial AB5 toxins

Additional file 7: of Genetic composition of captive panda population

Living wild founders without descendants in the captive population. (PDF 17 kb

Additional file 5: of Genetic composition of captive panda population

Genetic composition and inbreeding coefficients of hypothetical offspring of the 1630 mating pairs free of pedigree and hidden inbreeding. (XLSX 463 kb

Profile of microRNA in Giant Panda Blood: A Resource for Immune-Related and Novel microRNAs

<div><p>The giant panda (<i>Ailuropoda melanoleuca</i>) is one of the world’s most beloved endangered mammals. Although the draft genome of this species had been assembled, little was known about the composition of its microRNAs (miRNAs) or their functional profiles. Recent studies demonstrated that changes in the expression of miRNAs are associated with immunity. In this study, miRNAs were extracted from the blood of four healthy giant pandas and sequenced by Illumina next generation sequencing technology. As determined by miRNA screening, a total of 276 conserved miRNAs and 51 novel putative miRNAs candidates were detected. After differential expression analysis, we noticed that the expressions of 7 miRNAs were significantly up-regulated in young giant pandas compared with that of adults. Moreover, 2 miRNAs were up-regulated in female giant pandas and 1 in the male individuals. Target gene prediction suggested that the miRNAs of giant panda might be relevant to the expressions of 4,602 downstream genes. Subseuqently, the predicted target genes were conducted to KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis and we found that these genes were mainly involved in host immunity, including the Ras signaling pathway, the PI3K-Akt signaling pathway, and the MAPK signaling pathway. In conclusion, our results provide the first miRNA profiles of giant panda blood, and the predicted functional analyses may open an avenue for further study of giant panda immunity.</p></div

Partial secondary structure of novel miRNAs.

<p>The entire sequence represents pre-miRNAs.</p

Differentially expressed miRNAs in the male group and female individuals.

<p>Differentially expressed miRNAs in the male group and female individuals.</p

Category annotation for all samples.

<p>(A) Unique reads in F18. (B) Unique reads in M12. (C) Unique reads in F06. (D) Unique reads in M05.</p

Frequency distribution of sequence lengths of sequencing results in all samples.

<p>(A) The lengths for F18. (B)The lengths for M12. (C) The lengths for F06. (D) The lengths for M05.</p

Summary of miRNAs sequencing.

<p>Summary of miRNAs sequencing.</p

Differentially expressed miRNAs in the adult group and young individuals.

<p>Differentially expressed miRNAs in the adult group and young individuals.</p