A systematic review on impact of SARS-CoV-2 infection.

Innumerable pathogens including RNA viruses have catastrophic pandemic propensity, in turn, SARS-CoV-2 infection is highly contagious. Emergence of SARS-CoV-2 variants with high mutation rate additionally codifies infectious ability of virus and arisen clinical imputations to human health. Although, our knowledge of mechanism of virus infection and its impact on host system has been substantially demystified, uncertainties about the emergence of virus are still not fully understood. To date, there are no potentially curative drugs are identified against the viral infection. Even though, drugs are repurposed in the initial period of infection, many are significantly negative in clinical trials. Moreover, the infection is dependent on organ status, co-morbid conditions, variant of virus and geographic region. This review article aims to comprehensively describe the SARS-CoV-2 infection and the impacts in the host cellular system. This review also briefly provides an overview of genome, proteome and metabolome associated risk to infection and the advancement of therapeutics in SARS-CoV-2 infection management.

Subsequent infection differentially affects the proteome of Caenorhabditis elegans by abrogating the intestinal cell proliferation.

With a wide range of bacterial infections growing, it has become a big challenge to the research field to combat the newly emerging diseases. Immuno-compromised patients are vulnerable to opportunistic infections. P. mirabilis, an opportunistic pathogen infects the nematode when the immune system is compromised. In the present study, the C. elegans was pre-exposed to S. aureus for a short term, and then consecutively infected with P. mirabilis. The primary infection caused by S. aureus makes the immune system of C. elegans vulnerable making it easy for P. mirabilis to colonize efficiently during subsequent exposure, thereby stimulating the immune system of the nematode. In this study, the C. elegans exposed to the pathogens (S. aureus 4 h/P. mirabilis 40 h and S. aureus 8 h/P. mirabilis 60 h time points) showed a substantial difference in the banding patterns of SDS-PAGE gel, when compared to their respective OP50 fed controls. 2-DE identified a total of 235 proteins from all the time points which had >2 fold regulation. The regulated protein spots were identified by MALDI-ToF/ToF analysis and one common protein CDC-25.1 was found to be regulated in all the comparative time points. CDC-25.1 seemed to down regulate during subsequent infection and up regulate in single infection. The transcriptomic regulation of cdc-25.1 also reflects the protein regulation. In addition to it, survival assay in cdc-25.1 mutant nematodes confirm the susceptibility of host during subsequent infection.

Enhanced Cellular Uptake and Sustained Transdermal Delivery of Collagen for Skin Regeneration.

The present study reports a method for transporting high molecular weight collagen for skin regeneration. An independent engineered enzymatic vehicle that has the ability for efficient transdermal delivery of regenerative biomaterial was developed for tissue regeneration. Collagen has been well recognized as a skin regeneration molecule due to its interaction with the extracellular matrix to stimulate skin cell growth, proliferation, and differentiation. However, the transdermal delivery of collagen poses a significant challenge due to its high molecular weight as well as a lack of efficient approaches. Here, to improve the transdermal delivery efficiency, α-1,4-glycosidic hydrolase was engineered with genetically encoded 3,4-dihydroxy-L-phenylalanine, which enhanced its biological activity as revealed by microscale thermophoresis. The remodeled catalytic pocket resulted in enhanced substrate binding activity of the enzyme with a predominant glycosaminoglycan (chondroitin sulfate) present in the extracellular matrix of the skin. The engineered enzyme rapidly opened up the skin extracellular matrix fiber (15 min) to ferry collagen across the wall, without disturbing the cellular bundle architecture. Confocal microscopy indicated that macromolecules had diffused three times deeper into the engineered enzyme-treated skin than the native enzyme-treated skin. Gene expression, histopathology, and hematology analysis also supported the penetration of macromolecules. Cytotoxicity (mammalian cell culture) and in vivo (Caenorhabditis elegans and Rattus noryegicus) studies revealed that the congener enzyme could potentially be used as a penetration enhancer, which is of paramount importance for the multimillion cosmetic industries. Hence, it offers promise as a pharmaceutical enzyme for transdermal delivery bioenhancement and dermatological applications.

Bifid Shape Is Intrinsic to Bifidobacterium adolescentis.

Although the genus Bifidobacterium was originally named for its bifid morphology, not all bifidobacterial species have a similar structure, and very few of them adopt a bifid shape under stress conditions. The exposure of respective bifidobacterial species to various conditions, such as different pH, temperatures, medium components, in vivo growth in Caenorhabditis elegans, and subculture, did not affect their diverse morphologies. Extensive scanning electron microscopy studies suggested that the bifid shape of B. adolescentis are maintained irrespective of the conditions. Hence, we conclude that the bifid morphology is intrinsic to B. adolescentis. Most bifidobacterial species are anaerobic and rod-shaped, whereas, after the first generation, they become microaerophilic or aerophilic. CaCl2 (treatment of B. animalis) signaling triggered a change from the rod shape to the bifid shape and vice versa in B. adolescentis.

Proteome analysis reveals translational inhibition of Caenorhabditis elegans enhances susceptibility to Pseudomonas aeruginosa PAO1 pathogenesis.

UNLABELLED: Caenorhabditis elegans-Pseudomonas aeruginosa infection model is commonly used for pathogenesis studies over the decades. In the present study, upon exposure to the Pseudomonas aeruginosa PAO1, the 2D-PAGE was performed to examine the total proteins differences of C. elegans during the PAO1 infection at different time durations (12-48h). Also, the 2D-DIGE using the cyanine dyes were performed (48h) to identify the differentially regulated proteins against the PAO1 infection. Among the 19 short-listed proteins, 5 proteins were down-regulated and 14 proteins were up-regulated. Eukaryotic elongation factor-2 (EEF-2), a GTP binding protein involves in protein elongation process was down regulated during the pathogen infection. The 2D-PAGE analysis and MS data for the 12 and 24h infections identified the NDK-1 and other essential protein includes, ACS-18, ACT-1, GPD-3, GDH-1 and LBP-6 which are involved in important cellular homeostasis were down regulated. Validation studies using qPCR analysis for eef-2 and other selected genes, western blot analysis for EEF-2 and effect of host translational inhibition studies using Cycloheximide during PAO1 infection suggests that P. aeruginosa systematically restrains the function of host by arresting the expression of EEF-2 and thereby inhibiting protein translational events. Further, in silico analysis revealed the Exotoxin A could directly bind with the host EEF-2 and NDK-1 during the C. elegans- PAO1 interactions. BIOLOGICAL SIGNIFICANCE: Model system, C. elegans facilitates the identification of virulence mechanisms during bacterial pathogenesis. Upon infection by the fungal and bacterial pathogens, the C. elegans system induces an array of transcriptional responses, including differential expression of effector/modulator genes that provide safeguard and fight against infection. However, the in-depth knowledge of host response by the pathogen at protein level remains unclear. Much of the studies were carried out only at the transcripts level and scarce reports are available at the protein level for the host-pathogen interaction studies. In order to provide few interesting clues at the protein level, the nematode, C. elegans was infected with the human pathogen P. aeruginosa and the response(s) of host was investigated at the protein level by 2D-DIGE analysis and further validation studies using qPCR and western blotting techniques. Our differential proteomics data suggest that translational inhibition as one of the patterns of pathogenesis in C. elegans during P. aeruginosa infection. Since many of the effectors identified through C. elegans are conserved in other systems including human, our data pave the way for understanding important regulatory pathways involved during bacterial pathogenesis that can be translated into higher eukaryotic organisms.