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1.
Adrin Martínez-Melndez Flora Cruz-Lpez Rayo Morfin-Otero Hctor J. Maldonado-Garza Elvira Garza-Gonzlez 《Toxins》2022,14(5)
Infection with Clostridioides difficile (CDI), a common healthcare-associated infection, includes symptoms ranging from mild diarrhea to severe cases of pseudomembranous colitis. Toxin A (TcdA) and toxin B (TcdB) cause cytotoxicity and cellular detachment from intestinal epithelium and are responsible for CDI symptomatology. Approximately 20% of C. difficile strains produce a binary toxin (CDT) encoded by the tcdA and tcdB genes, which is thought to enhance TcdA and TcdB toxicity; however, the role of CDT in CDI remains controversial. Here, we focused on describing the main features of CDT and its impact on the host, clinical relevance, epidemiology, and potential therapeutic approaches. 相似文献
2.
Clostridium difficile toxin A (TcdA) and toxin B (TcdB) are the causative agent of the C. difficile-associated diarrhea (CDAD) and its severe form, the pseudomembranous colitis (PMC). TcdB from the C. difficile strain VPI10463 mono-glucosylates (thereby inactivates) the small GTPases Rho, Rac, and Cdc42, while Toxin B from the variant C. difficile strain serotype F 1470 (TcdBF) specifically mono-glucosylates Rac but not Rho(A/B/C). TcdBF is related to lethal toxin from C. sordellii (TcsL) that glucosylates Rac1 but not Rho(A/B/C). In this study, the effects of Rho-inactivating toxins on the concentrations of cellular F-actin were investigated using the rhodamine-phalloidin-based F-actin ELISA. TcdB induces F-actin depolymerization comparable to the RhoA-inactivating exoenzyme C3 from C. limosum (C3-lim). In contrast, the Rac-glucosylating toxins TcdBF and TcsL did not cause F-actin depolymerization. These observations led to the conclusion that F-actin depolymerization depends on the toxin’s capability of glucosylating RhoA. Furthermore, the integrity of focal adhesions (FAs) was analyzed using paxillin and p21-activated kinase (PAK) as FA marker proteins. Paxillin dephosphorylation was observed upon treatment of cells with TcdB, TcdBF, or C3-lim. In conclusion, the Rho-inactivating toxins induce loss of cell shape by either F-actin depolymerization (upon RhoA inactivation) or the disassembly of FAs (upon Rac1 inactivation). 相似文献
3.
Dan Wu Antony George Joyee Saravanan Nandagopal Marianela Lopez Xiuli Ma Jody Berry Francis Lin 《Toxins》2013,5(5):926-938
Bacterial products such as toxins can interfere with a variety of cellular processes, leading to severe human diseases. Clostridium difficile toxins, TcdA and TcdB are the primary contributing factors to the pathogenesis of C. difficile-associated diseases (CDAD). While the mechanisms for TcdA and TcdB mediated cellular responses are complex, it has been shown that these toxins can alter chemotactic responses of neutrophils and intestinal epithelial cells leading to innate immune responses and tissue damages. The effects of C. difficile toxins on the migration and trafficking of other leukocyte subsets, such as T lymphocytes, are not clear and may have potential implications for adaptive immunity. We investigated here the direct and indirect effects of TcdA and TcdB on the migration of human blood T cells using conventional cell migration assays and microfluidic devices. It has been found that, although both toxins decrease T cell motility, only TcdA but not TcdB decreases T cell chemotaxis. Similar effects are observed in T cell migration toward the TcdA- or TcdB-treated human epithelial cells. Our study demonstrated the primary role of TcdA (compared to TcdB) in altering T cell migration and chemotaxis, suggesting possible implications for C. difficile toxin mediated adaptive immune responses in CDAD. 相似文献
4.
5.
The major virulence factors of Clostridium difficile infection (CDI) are two large exotoxins A (TcdA) and B (TcdB). However, our understanding of the specific roles of these toxins in CDI is still evolving. It is now accepted that both toxins are enterotoxic and proinflammatory in the human intestine. Both purified TcdA and TcdB are capable of inducing the pathophysiology of CDI, although most studies have focused on TcdA. C. difficile toxins exert a wide array of biological activities by acting directly on intestinal epithelial cells. Alternatively, the toxins may target immune cells and neurons once the intestinal epithelial barrier is disrupted. The toxins may also act indirectly by stimulating cells to produce chemokines, proinflammatory cytokines, neuropeptides and other neuroimmune signals. This review considers the mechanisms of TcdA- and TcdB-induced enterotoxicity, and recent developments in this field. 相似文献
6.
Maria R. Romano Rosanna Leuzzi Emilia Cappelletti Marta Tontini Alberto Nilo Daniela Proietti Francesco Berti Paolo Costantino Roberto Adamo Maria Scarselli 《Toxins》2014,6(4):1385-1396
Clostridium difficile is a Gram-positive bacterium and is the most commonly diagnosed cause of hospital-associated and antimicrobial-associated diarrhea. Despite the emergence of epidemic C. difficile strains having led to an increase in the incidence of the disease, a vaccine against this pathogen is not currently available. C. difficile strains produce two main toxins (TcdA and TcdB) and express three highly complex cell-surface polysaccharides (PSI, PSII and PSIII). PSII is the more abundantly expressed by most C. difficile ribotypes offering the opportunity of the development of a carbohydrate-based vaccine. In this paper, we evaluate the efficacy, in naive mice model, of PSII glycoconjugates where recombinant toxins A and B fragments (TcdA_B2 and TcdB_GT respectively) have been used as carriers. Both glycoconjugates elicited IgG titers anti-PSII although only the TcdB_GT conjugate induced a response comparable to that obtained with CRM197. Moreover, TcdA_B2 and TcdB_GT conjugated to PSII retained the ability to elicit IgG with neutralizing activity against the respective toxins. These results are a crucial proof of concept for the development of glycoconjugate vaccines against C. difficile infection (CDI) that combine different C. difficile antigens to potentially prevent bacterial colonization of the gut and neutralize toxin activity. 相似文献
7.
In the attempt to improve the purification yield of native toxin A (TcdA) and toxin B (TcdB) from Clostridioides difficile (C. difficile), we systematically evaluated culture parameters for their influence on toxin production. In this study, we showed that culturing C. difficile in a tryptone-yeast extract medium buffered in PBS (pH 7.5) that contained 5 mM ZnCl2 and 10 mM glucose supported the highest TcdB production, measured by the sandwich ELISA. These culture conditions were scalable into 5 L and 15 L dialysis tube cultures, and we were able to reach a TcdB concentration of 29.5 µg/mL of culture. Furthermore, we established a purification protocol for TcdA and TcdB using FPLC column chromatography, reaching purities of >99% for both toxins with a yield around 25% relative to the starting material. Finally, by screening the melting temperatures of TcdA and TcdB in various buffer conditions using differential scanning fluorimetry, we found optimal conditions for improving the protein stability during storage. The results of this study present a complete protocol for obtaining high amounts of highly purified native TcdA and TcdB from C. difficile. 相似文献
8.
Kreimeyer I Euler F Marckscheffel A Tatge H Pich A Olling A Schwarz J Just I Gerhard R 《Naunyn-Schmiedeberg's archives of pharmacology》2011,383(3):253-262
Toxin A and toxin B from Clostridium difficile are the causative agents of the antibiotic-associated pseudomembranous colitis. They are of an A/B structure type and possess
inositol hexakisphosphate-inducible autoproteolytic activity to release their glucosyltransferase domain to the cytoplasm
of target cells. In this study, we investigated the effect of extracellular and intracellular autoproteolytic cleavage on
the function of TcdA. Extracellular cleavage led to functional inactivation albeit TcdA was less susceptible to inositol hexakisphosphate-induced
autoproteolysis than TcdB. A non-cleavable TcdA mutant (TcdA A541 G542 A543) was generated to investigate whether autoproteolysis
is a prerequisite for intracellular function of TcdA. Although the EC50 regarding cell rounding was about 75-fold reduced in short-term assay, non-cleavable TcdA was able to induce complete cell
rounding and apoptosis after 36 h comparable to wildtype TcdA when continuously present. Studies with limited uptake of toxins
revealed progressive Rac1 glucosylation and complete cell rounding for TcdA, whereas the effect induced by non-cleavable TcdA
was reversible. These findings argue for cytosolic accumulation of the released glucosyltransferase domain of wild-type TcdA
and rapid degradation of the non-cleavable TcdA. In summary, extracellular cleavage functionally inactivates TcdA (and TcdB),
whereas intracellular autoproteolytic cleavage is not essential for function of TcdA but defines its potency. 相似文献
9.
Alexandra Olling Corinna Hüls Sebastian Goy Mirco Müller Simon Krooss Isa Rudolf Helma Tatge Ralf Gerhard 《Toxins》2014,6(7):2162-2176
Toxin A (TcdA) and B (TcdB) from Clostridium difficile enter host cells by receptor-mediated endocytosis. A prerequisite for proper toxin action is the intracellular release of the glucosyltransferase domain by an inherent cysteine protease, which is allosterically activated by inositol hexaphosphate (IP6). We found that in in vitro assays, the C-terminally-truncated TcdA1–1065 was more efficient at IP6-induced cleavage compared with full-length TcdA. We hypothesized that the C-terminally-located combined repetitive oligopeptides (CROPs) interact with the N-terminal part of the toxin, thereby preventing autoproteolysis. Glutathione-S-transferase (GST) pull-down assays and microscale thermophoresis confirmed binding between the CROPs and the glucosyltransferase (TcdA1–542) or intermediate (TcdA1102–1847) domain of TcdA, respectively. This interaction between the N- and C-terminus was not found for TcdB. Functional assays revealed that TcdB was more susceptible to inactivation by extracellular IP6-induced cleavage. In vitro autoprocessing and inactivation of TcdA, however, significantly increased, either by acidification of the surrounding milieu or following exchange of its CROP domain by the homologous CROP domain of TcdB. Thus, TcdA CROPs contribute to the stabilization and protection of toxin conformation in addition to function as the main receptor binding domain. 相似文献
10.
Katharina Ernst Marc Landenberger Julian Nieland Katharina Nrgaard Manfred Frick Giorgio Fois Roland Benz Holger Barth 《Toxins》2021,13(6)
The clinically highly relevant Clostridioides (C.) difficile releases several AB-type toxins that cause diseases such as diarrhea and pseudomembranous colitis. In addition to the main virulence factors Rho/Ras-glycosylating toxins TcdA and TcdB, hypervirulent strains produce the binary AB-type toxin CDT. CDT consists of two separate proteins. The binding/translocation B-component CDTb facilitates uptake and translocation of the enzyme A-component CDTa to the cytosol of cells. Here, CDTa ADP-ribosylates G-actin, resulting in depolymerization of the actin cytoskeleton. We previously showed that CDTb exhibits cytotoxicity in the absence of CDTa, which is most likely due to pore formation in the cytoplasmic membrane. Here, we further investigated this cytotoxic effect and showed that CDTb impairs CaCo-2 cell viability and leads to redistribution of F-actin without affecting tubulin structures. CDTb was detected at the cytoplasmic membrane in addition to its endosomal localization if CDTb was applied alone. Chloroquine and several of its derivatives, which were previously identified as toxin pore blockers, inhibited intoxication of Vero, HCT116, and CaCo-2 cells by CDTb and CDTb pores in vitro. These results further strengthen pore formation by CDTb in the cytoplasmic membrane as the underlying cytotoxic mechanism and identify pharmacological pore blockers as potent inhibitors of cytotoxicity induced by CDTb and CDTa plus CDTb. 相似文献
11.
《Expert opinion on therapeutic patents》2013,23(12):1635-1640
Introduction: Incidence and severity of Clostridium difficile infection (CDI) are increasing worldwide. Toxins A (TcdA) and B (TcdB) and host immune response are the major determinates of CD pathogenesis and represent a new, stimulating therapeutic target to control CDI. Areas covered: The present patent and literature on the pathogenesis and treatment of CD were critically reviewed. The patent was described and put into clinical context, highlighting possible advantages and barriers to use. It consists of a blend of monoclonal antibodies (mAbs) and antigen-binding portions that neutralize TcdA, targeting the enterocyte-binding domain. It demonstrated good efficacy in in vivo models and seems promising in clinical practice. However, recent evidence reshaped the central role of TcdA. Expert opinion: Current treatments are inadequate to control CDI and recurrence. Toxin-targeted mAbs are one of the most promising approaches for CDI, including infection by hypervirulent strains. At-risk subjects and those experiencing recurrence are the ideal targets for this second-line treatment; however CDI epidemiology is fast-changing and mAbs may represent a powerful option also for other patients. The re-evaluation of the pathogenic role of TcdA may potentially limit the use of this product; however, the possible administration in combination with other therapeutic agents may optimize its efficacy. 相似文献
12.
Lica M Schulz F Schelle I May M Just I Genth H 《Naunyn-Schmiedeberg's archives of pharmacology》2011,383(3):275-283
Toxin A (TcdA) and toxin B (TcdB) from Clostridium difficile are the causative agents of the C. difficile-associated diarrhea (CDAD) and its severe form, the pseudomembranous colitis. TcdA and TcdB both glucosylate and thereby
inactivate low molecular weight GTP-binding proteins of the Rho, Rac, and Cdc42 subfamilies. In cultured cell lines, TcdB
induces actin re-organization and bi-nucleation (“cytopathic effects”) and cell death (“cytotoxic effects”). In this study,
the role of cell cycle progression in the cytopathic and the cytotoxic effects of TcdB is evaluated by a differential analysis
of these effects in proliferating and non-proliferating cells. Density-synchronized murine fibroblasts and confluent HT29
colonocytes are exploited as cell culture models for non-proliferating cells. Cell death is analyzed in terms of a loss of
cell viability, phosphatidylserine exposure, and DNA fragmentation. In proliferating cells, TcdB blocks cell proliferation
and induces apoptotic cell death. In contrast, TcdB induces non-apoptotic cell death in non-proliferating cells. TcdB-induced
cell rounding turns out to be independent of cell cycle progression. Cell cycle progression is an important determinant in
the biological effects of TcdB. With respect to the pathology of CDAD, this study leads to the new hypothesis that necrotic
cell death of terminally differentiated colonocytes and inhibition of epithelial renewal of the colon contribute to the pathogenesis
of CDAD. 相似文献
13.
目的:肠毒素A(TcdA)和肠毒素B(TcdB)是艰难芽孢梭状杆菌主要的毒力因子,我们对已经获得的纯化的重组蛋白TcdA和TcdB与对应的天然肠毒素蛋白的活性和功能进行了比较。方法通过光学显微镜观察重组肠毒素和对应的天然肠毒素对肠上皮细胞的细胞病变作用、蛋白印迹实验观察对Rac1蛋白的糖基化作用,以及激光共聚焦显微镜观察肠毒素对肠上皮细胞骨架的破坏作用。结果纯化得到重组蛋白肠毒素TcdA和rTcdB其分子量与天然的TcdA和TcdB蛋白大小接近,生物活性与天然的TcdB蛋白相似,TcdA和极微量TcdB具有使肠上皮细胞病变、Rac1蛋白的糖基、细胞骨架塌陷。结论艰难梭状芽孢杆菌肠毒素A和B重组蛋白具有良好的对应天然肠毒素相似的生物学功能活性。 相似文献
14.
T. Doménech J. Beleta J. M. Palacios 《Naunyn-Schmiedeberg's archives of pharmacology》1997,356(3):328-334
Clostridium difficile toxin B that inactivates Rho subfamily proteins by glucosylation, inhibited dinitrophenyl-conjugated bovine serum albumin
(DNP-BSA) and phorbol 12-myristate 13-acetate (PMA)-induced mast cell activation by 80 to 90% in a concentration- and time
dependent manner with a delay of about 30 min. Activation of mast cells by compound 48/80 and calcium ionophore A23187 was
maximally inhibited by about 50%. Inhibition by toxin B was observed with suspended, attached and permeabilised mast cells.
C3 ADP-ribosyltransferase, which selectively inactivates RhoA,B,C subtype proteins inhibited antigen, compound 48/80, PMA,
A23187 and GTP[S]-induced degranulation of permeabilised mast cells. C3-induced inhibition of stimulated histamine release
was smaller than that observed with toxin B and both inhibitory effects were not additive. These findings suggest the involvement
of Rho subtype GTPases and, additionally, of other members of the Rho subfamily GTPases in activation of rat peritoneal mast
cells.
Received: 7 October 1996 / Accepted: 22 November 1996 相似文献
15.
Callum J. Vidor Audrey Hamiot Jessica Wisniewski Rommel A. Mathias Bruno Dupuy Milena Awad Dena Lyras 《Toxins》2022,14(2)
Protein secretion is generally mediated by a series of distinct pathways in bacteria. Recently, evidence of a novel bacterial secretion pathway involving a bacteriophage-related protein has emerged. TcdE, a holin-like protein encoded by toxigenic isolates of Clostridioides difficile, mediates the release of the large clostridial glucosylating toxins (LCGTs), TcdA and TcdB, and TpeL from C. perfringens uses another holin-like protein, TpeE, for its secretion; however, it is not yet known if TcdE or TpeE secretion is specific to these proteins. It is also unknown if other members of the LCGT-producing clostridia, including Paeniclostridium sordellii (previously Clostridium sordellii), use a similar toxin-release mechanism. Here, we confirm that each of the LCGT-producing clostridia encode functional holin-like proteins in close proximity to the toxin genes. To characterise the respective roles of these holin-like proteins in the release of the LCGTs, P. sordellii and its lethal toxin, TcsL, were used as a model. Construction and analysis of mutants of the P. sordellii tcsE (holin-like) gene demonstrated that TcsE plays a significant role in TcsL release. Proteomic analysis of the secretome from the tcsE mutant confirmed that TcsE is required for efficient TcsL secretion. Unexpectedly, comparative sample analysis showed that TcsL was the only protein significantly altered in its release, suggesting that this holin-like protein has specifically evolved to function in the release of this important virulence factor. This specificity has, to our knowledge, not been previously shown and suggests that this protein may function as part of a specific mechanism for the release of all LCGTs. 相似文献
16.
Gudrun Schmid Annette Schürmann Christine Huppertz Fred Hofmann Klaus Aktories H.-G. Joost 《Naunyn-Schmiedeberg's archives of pharmacology》1998,357(4):385-392
The role of the actin cytoskeleton and/or GTPases of the Rho/Rac-family in glucose transport regulation was investigated in
3T3-L1 cells with clostridial toxins which depolymerize actin by inactivation of Rho/Rac (Clostridium difficile toxin B and Clostridium sordellii lethal toxin (LT)) or by direct ADP-ribosylation (Clostridium botulinum C2 toxin). Toxin B and C2 reduced insulin-stimulated, but not basal, 2-deoxyglucose (2-DOG) uptake rates in 3T3-L1 fibroblasts.
In parallel, the toxins produced morphological alterations of the cells reflecting disruption of the actin cytoskeleton. Both
toxins reduced the maximum response to insulin but failed to alter the half-maximally stimulating concentrations of insulin.
In 3T3-L1 adipocytes, the lethal toxin reduced the effect of insulin on 2-DOG uptake, whereas toxin B and C2 failed to affect
glucose transport or cell morphology. When cells were exposed to the toxins after treatment with insulin, both toxin B and
the lethal toxin, in contrast to the phosphatidylinositol (PI) 3-kinase inhibitor wortmannin, failed to reduce the 2-DOG uptake
rates. Thus, both translocation to the plasma membrane and internalization of glucose transporters were inhibited by the toxins,
whereas the PI 3-kinase inhibitor selectively affects translocation. The data suggest that the effects of the clostridial
toxins on trafficking of glucose transporters are mediated by the depolymerization of the actin cytoskeleton and are an indirect
consequence of Rho or Rac inactivation. It is suggested that pathways signalling through Rac or Rho may play a modulatory
role in glucose transport regulation through their effects on the actin network.
Received: 28 October 1997 / Accepted: 19 January 1998 相似文献
17.
Ahmed AbdelKhalek Nader S. Abutaleb Haroon Mohammad Mohamed N. Seleem 《International journal of antimicrobial agents》2019,53(1):54-62
Clostridium difficile is a deadly, opportunistic bacterial pathogen. In the last two decades, C. difficile infections (CDIs) have become a national concern because of the emergence of hypervirulent mutants with increased capability to produce toxins and spores. This has resulted in an increased number of infections and deaths associated with CDI. The scarcity of anticlostridial drugs has led to unsatisfactory cure rates, elevated recurrence rates and permitted enhanced colonization with other drug-resistant pathogens (such as vancomycin-resistant enterococci) in afflicted patients. Therefore, both patients and physicians are facing an urgent need for more effective therapies to treat CDI. In an effort to find new anticlostridial drugs, we investigated auranofin, an FDA-approved oral antirheumatic drug that has recently been found to possess antibacterial activity. Auranofin exhibited potent activity against C. difficile isolates, inhibiting growth at a concentration of 1 µg/mL against 50% of all tested isolates. Auranofin inhibited both toxin production and spore formation, a property lacking in both vancomycin and metronidazole (the primary agents used to treat CDI). Auranofin had a direct protective activity against C. difficile toxin-mediated inflammation and inhibited the growth of vancomycin-resistant enterococci. Auranofin is a promising candidate that warrants further investigation as a treatment option for C. difficile infections. 相似文献
18.
Botulinum neurotoxins (BoNTs) are potent bacterial toxins. The high oral toxicity of BoNTs is largely attributed to the progenitor toxin complex (PTC), which is assembled from BoNT and nontoxic neurotoxin-associated proteins (NAPs) that are produced together with BoNT in bacteria. Here, we performed ex vivo studies to examine binding of the highly homogeneous recombinant NAPs to mouse small intestine. We also carried out the first comprehensive glycan array screening with the hemagglutinin (HA) component of NAPs. Our data confirmed that intestinal binding of the PTC is partly mediated by the HA moiety through multivalent interactions between HA and host carbohydrates. The specific HA-carbohydrate recognition could be inhibited by receptor-mimicking saccharides. 相似文献
19.
Schmeck B Beermann W van Laak V Opitz B Hocke AC Meixenberger K Eitel J Chakraborty T Schmidt G Barth H Suttorp N Hippenstiel S 《Biochemical pharmacology》2006,72(11):1367-1374
Infection of endothelial cells by Listeria monocytogenes is an essential step in the pathogenesis of listeriosis. Small GTPases of the Rho family act as molecular switches in signal transduction. We tested the hypothesis that Rho GTPases contribute to the regulation of cytokine expression following L. monocytogenes infection. L. monocytogenes induced release of distinct CC and CXC, as well as Th1 and Th2 cytokines and growth factors by endothelial cells and activated RhoA and Rac1. Inhibition of Rac1 by inhibitor Nsc23766 reduced cytokine expression, and slightly yet significantly the uptake of bacteria. Blocking of Rho proteins by Clostridium difficile toxin B-10463 (TcdB) reduced Listeria-dependent cytokine expression, whereas activating Rho proteins by Escherichia coli CNF1 increased it. We analyzed regulation of IL-8 expression in more detail: Listeria-induced IL-8 release was reduced by inhibition of RhoA, Rac1 and Cdc42 (TcdB) or Rac1 while blocking of RhoA/B/C by Clostridium limosum C3 fusion toxin (C3FT) or Rho kinase by Y27632 reduced cytokine expression only slightly. Activation of RhoA, Rac1 and Cdc42 (CNF1), but not of RhoA alone (CNF(Y)), enhanced Listeria-dependent IL-8 release significantly. Furthermore, inhibition of RhoA, Rac1 and Cdc42 (TcdB) and Rac1 (Nsc23766), but not of RhoA (C3FT) reduced Listeria-related recruitment of NF-kappaB/p65 and RNA polymerase II to the il8 promoter, as well as acetylation of histone H4 and Ser10/Lys14-phosphorylation/acetylation of histone H3 at the il8 gene promoter in HUVEC. In conclusion, Rac1 contributed to L. monocytogenes-induced cytokine expression by human endothelial cells. 相似文献
20.
Guillaume Tetreau Elena A. Andreeva Anne-Sophie Banneville Elke De Zitter Jacques-Philippe Colletier 《Toxins》2021,13(7)
Bacillus thuringiensis (Bt) is a natural crystal-making bacterium. Bt diversified into many subspecies that have evolved to produce crystals of hundreds of pesticidal proteins with radically different structures. Their crystalline form ensures stability and controlled release of these major virulence factors. They are responsible for the toxicity and host specificity of Bt, explaining its worldwide use as a biological insecticide. Most research has been devoted to understanding the mechanisms of toxicity of these toxins while the features driving their crystallization have long remained elusive, essentially due to technical limitations. The evolution of methods in structural biology, pushing back the limits in size of amenable protein crystals now allows access to be gained to structural information hidden within natural crystals of such toxins. In this review, we present the main parameters that have been identified as key drivers of toxin crystallization in Bt, notably in the light of recent discoveries driven by structural biology studies. Then, we develop how the future evolution of structural biology will hopefully unveil new mechanisms of Bt toxin crystallization, opening the door to their hijacking with the aim of developing a versatile in vivo crystallization platform of high academic and industrial interest. 相似文献