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

Enhanced Photocatalytic Activity of Calix[4]arene-Based Donor–Acceptor Covalent Organic Frameworks by Dual Cocatalysts

The distinctive characteristics of covalent organic frameworks (COFs), including their high surface area, adjustable porosity, and sturdy chemical structure, render them appealing for potential use in photocatalytic applications. Nonetheless, the full utilization of their photocatalytic activity has been hindered by the limited charge separation and migration efficiencies of COFs, along with high exciton binding energies. In this research, calix[4]arene (C4A) and thiazolo[5,4-d]thiazole (TzTz) were selected as electron donor and acceptor units, respectively, to produce C4A-TzTz-COF with donor–acceptor (D–A) properties, which represents one of the most effective approaches for promoting charge separation and transport in organic semiconductors. As a control, C4A-PA-COF was synthesized, and it was observed that the photocatalytic hydrogen evolution rate of C4A-TzTz-COF with donor–acceptor (D–A) features was 7.3 times greater than that of the former. Additionally, Ag nanoparticles (NPs) and Pt NPs were sequentially deposited on the surface of C4A-TzTz-COF. Ag NPs serve as providers of hot electrons under the localized surface plasmon resonance (LSPR) effect, with the hot electrons being injected at the conduction band of C4A-TzTz-COF. Pt NPs, acting as catalytically active sites, effectively capture hot electrons for cocatalysis. Ultimately, the donor–acceptor structure of Pt–Ag3.0/C4A-TzTz-COF, featuring a bimetallic system, significantly enhances the photocatalytic activity in the visible light range, leading to a 2.2-fold increase in the photocatalytic hydrogen evolution rate over C4A-TzTz-COF. The synergistic effects of the dual cocatalysts not only facilitate charge separation and transfer but also enable the efficient utilization of solar energy for sustainable energy conversion. This study provides valuable insights into the design and development of advanced COF-based photocatalytic materials with enhanced performance, paving the way for their widespread application in renewable energy and environmental remediation technologies

Characterization of the Gut Microbiota in the Red Panda (<i>Ailurus fulgens</i>)

<div><p>The red panda is the only living species of the genus <i>Ailurus</i>. Like giant pandas, red pandas are also highly specialized to feed mainly on highly fibrous bamboo. Although several studies have focused on the gut microbiota in the giant panda, little is known about the gut microbiota of the red panda. In this study, we characterized the fecal microbiota from both wild (n = 16) and captive (n = 6) red pandas using a pyrosequecing based approach targeting the V1-V3 hypervariable regions of the 16S rRNA gene. Distinct bacterial communities were observed between the two groups based on both membership and structure. Wild red pandas maintained significantly higher community diversity, richness and evenness than captive red pandas, the communities of which were skewed and dominated by taxa associated with Firmicutes. Phylogenetic analysis of the top 50 OTUs revealed that 10 of them were related to known cellulose degraders. To the best of our knowledge, this is the first study of the gut microbiota of the red panda. Our data suggest that, similar to the giant panda, the gut microbiota in the red panda might also play important roles in the digestion of bamboo.</p></div

Relative abundance of OTUs at the phylum (A) and genus (B) level in the fecal microbiota from wild and captive red pandas.

<p>Relative abundance of OTUs at the phylum (A) and genus (B) level in the fecal microbiota from wild and captive red pandas.</p

Principal coordinate analysis of the community membership (A) and structure (B) using Jaccard and Theta YC distances, respectively.

<p>Green squares and yellow circles represent captive and wild red panda bacterial communities, respectively. Distances between symbols on the ordination plot reflect relative dissimilarities in community memberships or structures.</p

Neighbor-joining tree showing the phylogenetic relationship among the top 50 OTUs in this study (red) with known cellulose degraders (blue) and OTUs identified in the giant panda (green).

<p>Different phyla were shaded by different colors: green, Firmicutes; purple, Actinobacteria; orange, Bacteroidetes; blue, Proteobacteria. All bootstrap values > 50% were shown on the tree.</p

Comparison of community alpha diversities between the wild and captive red pandas.

<p>Diversity was measured by inverse Simpson (A) and Shannon index (B); Richness (C) and evenness (D) were measured by the number of observed OTUs and Shannon Evenness index, respectively. The top and bottom boundaries of each box indicate the 75^th and 25^th quartile valudes, respectively. The black lines within each box represent the median values. Different lowercase letters above the boxplots indicate significant differences in alpha diversities between wild and captive pandas (P<0.001, Mann Whitney test).</p

OTUs differentially represented between wild and captive red pandas identified by linear discriminant analysis coupled with effect size (LEfSe).

<p>A. Histogram showing OTUs that are more abundant in wild (green color) or captive (red color) red pandas ranked by effect size. The distribution of the most differentially distributed OTUs: OTU001 (more abundant in captive red pandas) and OTU003 (more abundant in wild red pandas) were illustrated in B and C, respectively.</p