scholarly journals Common architecture of Tc toxins from human and insect pathogenic bacteria

2019 ◽  
Vol 5 (10) ◽  
pp. eaax6497 ◽  
Author(s):  
F. Leidreiter ◽  
D. Roderer ◽  
D. Meusch ◽  
C. Gatsogiannis ◽  
R. Benz ◽  
...  

Tc toxins use a syringe-like mechanism to penetrate the membrane and translocate toxic enzymes into the host cytosol. They are composed of three components: TcA, TcB, and TcC. Low-resolution structures of TcAs from different bacteria suggest a considerable difference in their architecture and possibly in their mechanism of action. Here, we present high-resolution structures of five TcAs from insect and human pathogens, which show a similar overall composition and domain organization. Essential structural features, including a trefoil protein knot, are present in all TcAs, suggesting a common mechanism of action. All TcAs form functional pores and can be combined with TcB-TcC subunits from other species to form active chimeric holotoxins. We identified a conserved ionic pair that stabilizes the shell, likely operating as a strong latch that only springs open after destabilization of other regions. Our results provide new insights into the architecture and mechanism of the Tc toxin family.

2019 ◽  
Author(s):  
Franziska Leidreiter ◽  
Daniel Roderer ◽  
Dominic Meusch ◽  
Christos Gatsogiannis ◽  
Roland Benz ◽  
...  

AbstractTc toxin complexes use a syringe-like mechanism to penetrate the membrane and translocate a toxic enzyme into the host cytosol. They are composed of three components: TcA, TcB and TcC. Until recently, low-resolution structures of TcA from different bacteria suggested that Tc toxins differ considerably in their architecture and possibly in their mechanism of action. Here, we present high-resolution structures and functional studies of five TcAs from different insect and human pathogenic bacteria. Contrary to previous expectations, their overall composition and domain organization is almost identical. The TcAs assemble as a pentamer with a central α-helical channel surrounded by a shell composed of conserved α-helical domains and variable β-sheet domains. Essential structural features, including a conserved trefoil protein knot, are present in all five TcAs, suggesting a common mechanism of action. All TcAs form functional pores and can be combined with TcB-TcC subunits from other species resulting in chimeric holotoxins. We have identified a conserved ionic pair that stabilizes the shell, likely operating as a strong latch that only springs open after the destabilization of other regions. Our results lead to new insights into the architecture and host specificity of the Tc toxin family.


Author(s):  
D. F. Blake ◽  
L. F. Allard ◽  
D. R. Peacor

Echinodermata is a phylum of marine invertebrates which has been extant since Cambrian time (c.a. 500 m.y. before the present). Modern examples of echinoderms include sea urchins, sea stars, and sea lilies (crinoids). The endoskeletons of echinoderms are composed of plates or ossicles (Fig. 1) which are with few exceptions, porous, single crystals of high-magnesian calcite. Despite their single crystal nature, fracture surfaces do not exhibit the near-perfect {10.4} cleavage characteristic of inorganic calcite. This paradoxical mix of biogenic and inorganic features has prompted much recent work on echinoderm skeletal crystallography. Furthermore, fossil echinoderm hard parts comprise a volumetrically significant portion of some marine limestones sequences. The ultrastructural and microchemical characterization of modern skeletal material should lend insight into: 1). The nature of the biogenic processes involved, for example, the relationship of Mg heterogeneity to morphological and structural features in modern echinoderm material, and 2). The nature of the diagenetic changes undergone by their ancient, fossilized counterparts. In this study, high resolution TEM (HRTEM), high voltage TEM (HVTEM), and STEM microanalysis are used to characterize tha ultrastructural and microchemical composition of skeletal elements of the modern crinoid Neocrinus blakei.


Author(s):  
ANNAMALAI MADURAM ◽  
RAJU KAMARAJ

Objectives: The objectives of the study were to study the antibacterial activity for the various extracts of Clausena dentata against human pathogens. Clausena (Rutaceae) is a genus of about 23 species of unarmed trees and shrubs. The stem bark of C. dentata is used in veterinary medicine for the treatment of wounds and sprains. Even though C. dentata has a lot of potential medical uses, the study of microbiological properties is very scarce. Methods: The plant C. dentata was collected from Kadagaman, near Tiruvannamalai, Tamil Nadu, India, and authenticated by Centre for Advanced Study in Botany, University of Madras, Chennai. The dry powder of stem bark was extracted with hexane, chloroform, and methanol. The extracts were subjected to qualitative phytochemical screening and antibacterial activity against human pathogenic bacteria such as Escherichia coli, Salmonella Typhi, Klebsiella pneumonia, Vibrio cholerae, and Staphylococcus aureus and compared with ciprofloxacin. Results: Qualitative chemical tests revealed the presence of various phytochemicals such as alkaloids, glycosides, carbohydrate, proteins and amino acids, phytosterols, and volatile oil. The antibacterial activity result reveals that all the extracts were are more active against V. cholerae. The activity against Pseudomonas aeruginosa was mild. Conclusion: The activity against V. cholerae was comparable with that of 5 μg/mL ciprofloxacin at the concentration of C. dentata 40 μg/mL. The orders of antibacterial activity against human pathogenic bacteria are hexane, methanol, and chloroform extract of C. dentata.


2021 ◽  
pp. 153537022199981
Author(s):  
Chamithi Karunanayake ◽  
Richard C Page

The chaperone heat shock protein 70 (Hsp70) and its network of co-chaperones serve as a central hub of cellular protein quality control mechanisms. Domain organization in Hsp70 dictates ATPase activity, ATP dependent allosteric regulation, client/substrate binding and release, and interactions with co-chaperones. The protein quality control activities of Hsp70 are classified as foldase, holdase, and disaggregase activities. Co-chaperones directly assisting protein refolding included J domain proteins and nucleotide exchange factors. However, co-chaperones can also be grouped and explored based on which domain of Hsp70 they interact. Here we discuss how the network of cytosolic co-chaperones for Hsp70 contributes to the functions of Hsp70 while closely looking at their structural features. Comparison of domain organization and the structures of co-chaperones enables greater understanding of the interactions, mechanisms of action, and roles played in protein quality control.


2021 ◽  
Vol 9 (1) ◽  
pp. 171
Author(s):  
Yitayal S. Anteneh ◽  
Qi Yang ◽  
Melissa H. Brown ◽  
Christopher M. M. Franco

The misuse and overuse of antibiotics have led to the emergence of multidrug-resistant microorganisms, which decreases the chance of treating those infected with existing antibiotics. This resistance calls for the search of new antimicrobials from prolific producers of novel natural products including marine sponges. Many of the novel active compounds reported from sponges have originated from their microbial symbionts. Therefore, this study aims to screen for bioactive metabolites from bacteria isolated from sponges. Twelve sponge samples were collected from South Australian marine environments and grown on seven isolation media under four incubation conditions; a total of 1234 bacterial isolates were obtained. Of these, 169 bacteria were tested in media optimized for production of antimicrobial metabolites and screened against eleven human pathogens. Seventy bacteria were found to be active against at least one test bacterial or fungal pathogen, while 37% of the tested bacteria showed activity against Staphylococcus aureus including methicillin-resistant strains and antifungal activity was produced by 21% the isolates. A potential novel active compound was purified possessing inhibitory activity against S. aureus. Using 16S rRNA, the strain was identified as Streptomyces sp. Our study highlights that the marine sponges of South Australia are a rich source of abundant and diverse bacteria producing metabolites with antimicrobial activities against human pathogenic bacteria and fungi.


Electronics ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1013
Author(s):  
Sayan Maity ◽  
Mohamed Abdel-Mottaleb ◽  
Shihab S. Asfour

Biometric identification using surveillance video has attracted the attention of many researchers as it can be applicable not only for robust identification but also personalized activity monitoring. In this paper, we present a novel multimodal recognition system that extracts frontal gait and low-resolution face images from frontal walking surveillance video clips to perform efficient biometric recognition. The proposed study addresses two important issues in surveillance video that did not receive appropriate attention in the past. First, it consolidates the model-free and model-based gait feature extraction approaches to perform robust gait recognition only using the frontal view. Second, it uses a low-resolution face recognition approach which can be trained and tested using low-resolution face information. This eliminates the need for obtaining high-resolution face images to create the gallery, which is required in the majority of low-resolution face recognition techniques. Moreover, the classification accuracy on high-resolution face images is considerably higher. Previous studies on frontal gait recognition incorporate assumptions to approximate the average gait cycle. However, we quantify the gait cycle precisely for each subject using only the frontal gait information. The approaches available in the literature use the high resolution images obtained in a controlled environment to train the recognition system. However, in our proposed system we train the recognition algorithm using the low-resolution face images captured in the unconstrained environment. The proposed system has two components, one is responsible for performing frontal gait recognition and one is responsible for low-resolution face recognition. Later, score level fusion is performed to fuse the results of the frontal gait recognition and the low-resolution face recognition. Experiments conducted on the Face and Ocular Challenge Series (FOCS) dataset resulted in a 93.5% Rank-1 for frontal gait recognition and 82.92% Rank-1 for low-resolution face recognition, respectively. The score level multimodal fusion resulted in 95.9% Rank-1 recognition, which demonstrates the superiority and robustness of the proposed approach.


Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3779
Author(s):  
Ruben Soto-Acosta ◽  
Eunkyung Jung ◽  
Li Qiu ◽  
Daniel J. Wilson ◽  
Robert J. Geraghty ◽  
...  

Discovery of compound 1 as a Zika virus (ZIKV) inhibitor has prompted us to investigate its 7H-pyrrolo[2,3-d]pyrimidine scaffold, revealing structural features that elicit antiviral activity. Furthermore, we have demonstrated that 9H-purine or 1H-pyrazolo[3,4-d]pyrimidine can serve as an alternative core structure. Overall, we have identified 4,7-disubstituted 7H-pyrrolo[2,3-d]pyrimidines and their analogs including compounds 1, 8 and 11 as promising antiviral agents against flaviviruses ZIKV and dengue virus (DENV). While the molecular target of these compounds is yet to be elucidated, 4,7-disubstituted 7H-pyrrolo[2,3-d]pyrimidines and their analogs are new chemotypes in the design of small molecules against flaviviruses, an important group of human pathogens.


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