scholarly journals Revisiting Bacterial Ubiquitin Ligase Effectors: Weapons for Host Exploitation

2018 ◽  
Vol 19 (11) ◽  
pp. 3576 ◽  
Author(s):  
Antonio Pisano ◽  
Francesco Albano ◽  
Eleonora Vecchio ◽  
Maurizio Renna ◽  
Giuseppe Scala ◽  
...  

Protein ubiquitylation plays a central role in eukaryotic cell physiology. It is involved in several regulatory processes, ranging from protein folding or degradation, subcellular localization of proteins, vesicular trafficking and endocytosis to DNA repair, cell cycle, innate immunity, autophagy, and apoptosis. As such, it is reasonable that pathogens have developed a way to exploit such a crucial system to enhance their virulence against the host. Hence, bacteria have evolved a wide range of effectors capable of mimicking the main players of the eukaryotic ubiquitin system, in particular ubiquitin ligases, by interfering with host physiology. Here, we give an overview of this topic and, in particular, we detail and discuss the mechanisms developed by pathogenic bacteria to hijack the host ubiquitination system for their own benefit.

2019 ◽  
Vol 63 (8-9-10) ◽  
pp. 529-539
Author(s):  
Barbara Pergolizzi ◽  
Salvatore Bozzaro ◽  
Enrico Bracco

By protein quality control and degradation, the ubiquitin system drives many essential regulatory processes such as cell cycle and division, signalling, DNA replication and repair. Therefore, dysfunctions in the ubiquitin system lead to many human disease states. However, despite the immense progress made over the last couple of decades, it appears that the ubiquitin system is more complex and multi-faced than formerly expected. In addition to a rich repertoire of ubiquitin, ubiquitin conjugating and de-ubiquitylating enzymes, the social amoeba Dictyostelium discoideum genome encodes also for a wide array of ubiquitin binding domain-containing proteins, thus offering the possibility to explore the biology of the ubiquitin system from cell and molecular biology points of view. We here provide an overview on the current knowledge about the Ub-system components and we discuss how Dictyostelium might be an outstanding eukaryotic cell model for unravelling the still mostly unknown ubiquitination mechanisms of some human diseases.


2020 ◽  
Vol 8 (2) ◽  
pp. 229 ◽  
Author(s):  
Hyein Jang ◽  
Gopal R. Gopinath ◽  
Athmanya Eshwar ◽  
Shabarinath Srikumar ◽  
Scott Nguyen ◽  
...  

Cronobacter species are considered an opportunistic group of foodborne pathogenic bacteria capable of causing both intestinal and systemic human disease. This review describes common virulence themes shared among the seven Cronobacter species and describes multiple exoproteins secreted by Cronobacter, many of which are bacterial toxins that may play a role in human disease. The review will particularly concentrate on the virulence factors secreted by C. sakazakii, C. malonaticus, and C. turicensis, which are the primary human pathogens of interest. It has been discovered that various species-specific virulence factors adversely affect a wide range of eukaryotic cell processes including protein synthesis, cell division, and ion secretion. Many of these factors are toxins which have been shown to also modulate the host immune response. These factors are encoded on a variety of mobile genetic elements such as plasmids and transposons; this genomic plasticity implies ongoing re-assortment of virulence factor genes which has complicated our efforts to categorize Cronobacter into sharply defined genomic pathotypes.


2021 ◽  
Vol 22 (10) ◽  
pp. 5394
Author(s):  
Tomas Lidak ◽  
Nikol Baloghova ◽  
Vladimir Korinek ◽  
Radislav Sedlacek ◽  
Jana Balounova ◽  
...  

Multisubunit cullin-RING ubiquitin ligase 4 (CRL4)-DCAF12 recognizes the C-terminal degron containing acidic amino acid residues. However, its physiological roles and substrates are largely unknown. Purification of CRL4-DCAF12 complexes revealed a wide range of potential substrates, including MOV10, an “ancient” RNA-induced silencing complex (RISC) complex RNA helicase. We show that DCAF12 controls the MOV10 protein level via its C-terminal motif in a proteasome- and CRL-dependent manner. Next, we generated Dcaf12 knockout mice and demonstrated that the DCAF12-mediated degradation of MOV10 is conserved in mice and humans. Detailed analysis of Dcaf12-deficient mice revealed that their testes produce fewer mature sperms, phenotype accompanied by elevated MOV10 and imbalance in meiotic markers SCP3 and γ-H2AX. Additionally, the percentages of splenic CD4+ T and natural killer T (NKT) cell populations were significantly altered. In vitro, activated Dcaf12-deficient T cells displayed inappropriately stabilized MOV10 and increased levels of activated caspases. In summary, we identified MOV10 as a novel substrate of CRL4-DCAF12 and demonstrated the biological relevance of the DCAF12-MOV10 pathway in spermatogenesis and T cell activation.


Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 460
Author(s):  
Mohammed Hamed Alqarni ◽  
Ahmed Ibrahim Foudah ◽  
Magdy Mohamed Muharram ◽  
Nikolaos E. Labrou

Sirtuins (SIRTs) are nicotinamide adenine dinucleotide-dependent histone deacetylases that incorporate complex functions in the mechanisms of cell physiology. Mammals have seven distinct members of the SIRT family (SIRT1-7), which play an important role in a well-maintained network of metabolic pathways that control and adapt the cell to the environment, energy availability and cellular stress. Until recently, very few studies investigated the role of SIRTs in modulating viral infection and progeny. Recent studies have demonstrated that SIRT1 and SIRT2 are promising antiviral targets because of their specific connection to numerous metabolic and regulatory processes affected during infection. In the present review, we summarize some of the recent progress in SIRTs biochemistry and their emerging function as antiviral targets. We also discuss the potential of natural polyphenol-based SIRT modulators to control their functional roles in several diseases including viral infections.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Luca Barbieri ◽  
Ioritz Sorzabal Bellido ◽  
Alison J. Beckett ◽  
Ian A. Prior ◽  
Jo Fothergill ◽  
...  

AbstractIn this work, we introduce a one-step strategy that is suitable for continuous flow manufacturing of antimicrobial PDMS materials. The process is based on the intrinsic capacity of PDMS to react to certain organic solvents, which enables the incorporation of antimicrobial actives such as salicylic acid (SA), which has been approved for use in humans within pharmaceutical products. By combining different spectroscopic and imaging techniques, we show that the surface properties of PDMS remain unaffected while high doses of the SA are loaded inside the PDMS matrix. The SA can be subsequently released under physiological conditions, delivering a strong antibacterial activity. Furthermore, encapsulation of SA inside the PDMS matrix ensured a diffusion-controlled release that was tracked by spatially resolved Raman spectroscopy, Attenuated Total Reflectance IR (ATR-IR), and UV-Vis spectroscopy. The biological activity of the new material was evaluated directly at the surface and in the planktonic state against model pathogenic bacteria, combining confocal laser scanning microscopy, electron microscopy, and cell viability assays. The results showed complete planktonic inhibition for clinically relevant strains of Staphylococcus aureus and Escherichia coli, and a reduction of up to 4 orders of magnitude for viable sessile cells, demonstrating the efficacy of these surfaces in preventing the initial stages of biofilm formation. Our approach adds a new option to existing strategies for the antimicrobial functionalisation of a wide range of products such as catheters, wound dressings and in-dwelling medical devices based on PDMS.


2021 ◽  
Vol 7 (8) ◽  
pp. 624
Author(s):  
Ulises Carrasco-Navarro ◽  
Jesús Aguirre

Reactive oxygen species (ROS) regulate several aspects of cell physiology in filamentous fungi including the antioxidant response and development. However, little is known about the signaling pathways involved in these processes. Here, we report Aspergillus nidulans global phosphoproteome during mycelial growth and show that under these conditions, H2O2 induces major changes in protein phosphorylation. Among the 1964 phosphoproteins we identified, H2O2 induced the phosphorylation of 131 proteins at one or more sites as well as the dephosphorylation of a larger set of proteins. A detailed analysis of these phosphoproteins shows that H2O2 affected the phosphorylation of critical regulatory nodes of phosphoinositide, MAPK, and TOR signaling as well as the phosphorylation of multiple proteins involved in the regulation of gene expression, primary and secondary metabolism, and development. Our results provide a novel and extensive protein phosphorylation landscape in A. nidulans, indicating that H2O2 induces a shift in general metabolism from anabolic to catabolic, and the activation of multiple stress survival pathways. Our results expand the significance of H2O2 in eukaryotic cell signaling.


Biologics ◽  
2021 ◽  
Vol 1 (2) ◽  
pp. 164-176
Author(s):  
Abdallah S. Abdelsattar ◽  
Anan Safwat ◽  
Rana Nofal ◽  
Amera Elsayed ◽  
Salsabil Makky ◽  
...  

Food safety is very important in the food industry as most pathogenic bacteria can cause food-borne diseases and negatively affect public health. In the milk industry, contamination with Salmonella has always been a challenge, but the risks have dramatically increased as almost all bacteria now show resistance to a wide range of commercial antibiotics. This study aimed to isolate a bacteriophage to be used as a bactericidal agent against Salmonella in milk and dairy products. Here, phage ZCSE6 has been isolated from raw milk sample sand molecularly and chemically characterized. At different multiplicities of infection (MOIs) of 0.1, 0.01, and 0.001, the phage–Salmonella interaction was studied for 6 h at 37 °C and 24 h at 8 °C. In addition, ZCSE6 was tested against Salmonella contamination in milk to examine its lytic activity for 3 h at 37 °C. The results showed that ZCSE6 has a small genome size (<48.5 kbp) and belongs to the Siphovirus family. Phage ZCSE6 revealed a high thermal and pH stability at various conditions that mimic milk manufacturing and supply chain conditions. It also demonstrated a significant reduction in Salmonella concentration in media at various MOIs, with higher bacterial eradication at higher MOI. Moreover, it significantly reduced Salmonella growth (MOI 1) in milk, manifesting a 1000-fold decrease in bacteria concentration following 3 h incubation at 37 °C. The results highlighted the strong ability of ZCSE6 to kill Salmonella and control its growth in milk. Thus, ZCSE6 is recommended as a biocontrol agent in milk to limit bacterial growth and increase the milk shelf-life.


2014 ◽  
Vol 6 (4) ◽  
pp. 478-482
Author(s):  
Razieh VALIASILL ◽  
Majid AZIZI ◽  
Maasome BAHREINI ◽  
Hossein AROUIE

Medicinal plants may be exposed to a wide range of microbial contamination during pre- and post- harvest stages and they can present high microbial counts. In this study, the microbial quality of 44 samples of dry herbs namely: mint (Menthaspp.), lemon balm (Melissa officinalis), summer savory (Satureja hortensis), zataria (Zataria multiflora), Indian valerian (Valeriana wallichii), their brewing and extracts were analyzed. Total count using plate count agar medium (PCA), coliform count by Violet Red Bile Agar (VRBL), Enterobacteriacea by Violet Red Bile Glucose (VRBG) were evaluated. Medium Baird-Parker agar (BP) medium and Tryptone Bile X-Gluc (TBX) medium were used for the isolation and enumeration of Staphylococcus aurous and E. coli spp. respectively. Furthermore, Xylose Lysine Deoxycholate agar medium (XLD) and Bismuth Sulfite Agar medium(BSA) were used for detection of Salmonella spp. Fungal and mold contamination was assessed using yeast extract glucose chloramphenicol agar. The results showed that the contamination of the samples with total count (100%) and Enterobacteriaceae (85%), total coliform (83%), mold and yeast (98%) and E. coli ssp. (2.27) were detected, including in the study samples the absence of pathogenic bacteria like Staphylococcus aurous, Salmonella spp. Moreover, the extract had a lower microbial load in comparison to dry herb samples. Also, the lowest and the highest of contamination rates were observed for Indian valerian and zataria, respectively. According to the results, there is a need to control the environmental conditions and improve hygiene in the production process; even more, it is recommended to choose a suitable decontamination method for disinfection during packing medicinal plants and during post-packing manipulation and transport.


2019 ◽  
Author(s):  
Aleksandar Vještica ◽  
Magdalena Marek ◽  
Pedro N’kosi ◽  
Laura Merlini ◽  
Gaowen Liu ◽  
...  

AbstractSchizosaccharomyces pombe is a widely used model organism that resembles higher eukaryotes in many aspects of cell physiology. Its popularity as an experimental system partially stems from the ease of genetic manipulations, where the innate homology-targeted repair is exploited to precisely edit the genome. While vectors to incorporate exogenous sequences into the chromosomes are available, most are poorly characterized. Here we show that commonly used fission yeast vectors, which upon integration produce repetitive genomic regions, yield unstable genomic loci. We overcome this problem by designing a new series of Stable Integration Vectors (SIV) that target four different prototrophy genes. SIV produce non-repetitive, stable genomic loci and integrate predominantly as single copy. Additionally, we develop a set of complementary auxotrophic alleles that preclude false-positive integration events. We expand the vector series to include antibiotic resistance markers, promoters, fluorescent tags and terminators, and build a highly modular toolbox to introduce heterologous sequences. Finally, as proof of concept, we generate a large set of ready-to-use, fluorescent probes to mark organelles and cellular processes with a wide range of applications in fission yeast research.


Algologia ◽  
2021 ◽  
Vol 31 (2) ◽  
pp. 126-140
Author(s):  
Le Dinh Hung ◽  
◽  
Vo Thi Dieu Trang ◽  

A new lectin from the marine red alga Gracilaria canaliculata (GCL) was isolated by a combination of aqueous ethanol extraction, ethanol precipitation, ion exchange and filtration chromatography. Lectin gave a single band with molecular mass of 22,000 Da in both non-reducing and reducing SDS-PAGE conditions, indicating that GCL is a monomeric protein. The hemagglutination activities of GCL were stable over a wide range of pH from 3 to 10, temperature up 60 oC and not affected by either the presence of EDTA or addition of divalent cations. Lectin GCL had high affinity for N-acetylneuraminic acid through interacting with the acetamido group at equatorial C2 position of these sugar residues, suggesting that GCL is specific for N-acetylneuraminic acid. Furthermore, GCL inhibited the growth of human and shrimp pathogenic bacteria, Staphylococcus aureus and Vibrio alginolyticus, although it did not affect the growth of Escherichia coli, Enterobacter cloace, Vibrio parahaemolyticus and V. harveyi. The red alga G. canaliculata may promise to be a source of valuable lectins for application as antibacterial agents.


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