Transcriptomic studies revealed pathophysiological impact of COVID-19 to predominant health conditions.

Despite the association of prevalent health conditions with coronavirus disease 2019 (COVID-19) severity, the disease-modifying biomolecules and their pathogenetic mechanisms remain unclear. This study aimed to understand the influences of COVID-19 on different comorbidities and vice versa through network-based gene expression analyses. Using the shared dysregulated genes, we identified key genetic determinants and signaling pathways that may involve in their shared pathogenesis. The COVID-19 showed significant upregulation of 93 genes and downregulation of 15 genes. Interestingly, it shares 28, 17, 6 and 7 genes with diabetes mellitus (DM), lung cancer (LC), myocardial infarction and hypertension, respectively. Importantly, COVID-19 shared three upregulated genes (i.e. MX2, IRF7 and ADAM8) with DM and LC. Conversely, downregulation of two genes (i.e. PPARGC1A and METTL7A) was found in COVID-19 and LC. Besides, most of the shared pathways were related to inflammatory responses. Furthermore, we identified six potential biomarkers and several important regulatory factors, e.g. transcription factors and microRNAs, while notable drug candidates included captopril, rilonacept and canakinumab. Moreover, prognostic analysis suggests concomitant COVID-19 may result in poor outcome of LC patients. This study provides the molecular basis and routes of the COVID-19 progression due to comorbidities. We believe these findings might be useful to further understand the intricate association of these diseases as well as for the therapeutic development.

A comprehensive screening of the whole proteome of hantavirus and designing a multi-epitope subunit vaccine for cross-protection against hantavirus: Structural vaccinology and immunoinformatics study.

Hantaviruses are an emerging zoonotic group of rodent-borne viruses that are having serious implications on global public health due to the increase in outbreaks. Since there is no permanent cure, there is increasing interest in developing a vaccine against the hantavirus. This research aimed to design a robust cross-protective subunit vaccine using a novel immunoinformatics approach. After careful evaluation, the best predicted cytotoxic & helper T-cell and B-cell epitopes from nucleocapsid proteins, glycoproteins, RdRp proteins, and non-structural proteins were considered as potential vaccine candidates. Among the four generated vaccine models with different adjuvant, the model with toll-like receptor-4 (TLR-4) agonist adjuvant was selected because of its high antigenicity, non-allergenicity, and structural quality. The selected model was 654 amino acids long and had a molecular weight of 70.5 kDa, which characterizes the construct as a good antigenic vaccine candidate. The prediction of the conformational B-lymphocyte (CBL) epitope secured its ability to induce the humoral response. Thereafter, disulfide engineering improved vaccine stability. Afterwards, the molecular docking confirmed a good binding affinity of -1292 kj/mol with considered immune receptor TLR-4 and the dynamics simulation showed high stability of the vaccine-receptor complex. Later, the in silico cloning confirmed the better expression of the constructed vaccine protein in E. coli K12. Finally, in in silico immune simulation, significantly high levels of immunoglobulin M (IgM), immunoglobulin G1 (IgG1), cytotoxic & helper T lymphocyte (CTL & HTL) populations, and numerous cytokines such as interferon-γ (IFN-γ), interleukin-2 (IL-2) etc. were found as coherence with actual immune response and also showed faster antigen clearance for repeated exposures. Nonetheless, experimental validation can demonstrate the safety and cross-protective ability of the proposed vaccine to fight against hantavirus infection.

Computational formulation and immune dynamics of a multi-peptide vaccine candidate against Crimean-Congo hemorrhagic fever virus.

The sole objective of this research is to devise an epitope-based vaccine candidate as prophylaxis for the Crimean-Congo hemorrhagic fever virus (CCHFV) using the knowledge of immunoinformatics and structural biology. Importantly, CCHFV outbreaks have increased in several countries resulting in increased mortality up to 40% due to the lack of prospective medication and an efficient vaccine. In this study, we have used several immunoinformatic tools and servers to anticipate potent B-cell and T-cell epitopes from the CCHFV glycoprotein with the highest antigenicity. After a comprehensive evaluation, a vaccine candidate was designed using 6 CD8+, 3 CD4+, and 7 B-cell epitopes with appropriate linkers. To enhance the vaccine's efficiency, we added Mycobacterium tuberculosis lipoprotein LprG (Rv1411c) to the vaccine as an adjuvant. The final construct was composed of a total of 468 amino acid residues. The epitope included in the construct showed 98% worldwide population coverage. Importantly, the construct appeared as antigenic, immunogenic, soluble, and non-allergenic in nature. To explore further, we modelled the three-dimensional (3D) structure of the constructed vaccine. Our chimeric vaccine showed stable and strong interactions for toll-like receptor 2 (TLR2) found on the cell surface. Moreover, the dynamics simulation of immune response showed elevated levels of cellular immune activity and faster clearance of antigen from the body upon repetitive exposure. Finally, the optimized codon (CAI≈1) ensured the marked translation efficiency of the vaccine protein in E. coli strain K12 bacterium followed by the insertion of construct DNA into the cloning vector pET28a (+). We believe that the designed vaccine chimera could be useful in vaccine development to fight CCHFV outbreaks.

Identification and antibiotic pattern analysis of bacillary dysentery causing bacteria isolated from stool samples of infected patients.

Bacillary dysentery is a type of dysentery and a severe form of shigellosis. This dysentery is usually restricted to Shigella infection, but Salmonella enterica and enteroinvasive Escherichia coli strains are also known as this infection's causative agents. The emergence of drug-resistant, bacillary dysentery-causing pathogens is a global burden, especially for developing countries with poor hygienic environments. This study aimed to isolate, identify, and determine the drug-resistant pattern of bacillary dysentery-causing pathogens from the stool samples of the Kushtia region in Bangladesh. Hence, biochemical tests, serotyping, molecular identification, and antibiotic profiling were performed to characterize the pathogens. Among one hundred fifty (150) stool samples, 18 enteric bacterial pathogens were isolated and identified, where 12 were Shigella strains, 5 were S. enterica sub spp. enterica strains and one was the E.coli strain. Among 12 Shigella isolates, 8 were Shigella flexneri 2a serotypes, and 4 were Shigella sonnei Phage-II serotypes. Except for three Salmonella strains, all isolated strains were drug-resistant (83%), whereas 50% were multidrug-resistant (MDR), an alarming issue for public health. In antibiotic-wise analysis, the isolated pathogens showed the highest resistance against nalidixic acid (77.78%), followed by tetracycline (38.89%), kanamycin (38.89%), amoxicillin (27.78%), streptomycin (27.78%), cefepime (22.22%), ceftriaxone (22.22%), ampicillin (16.67%), ciprofloxacin (16.67%), and chloramphenicol (16.67%). The existence of MDR organisms that cause bacillary dysentery in the Kushtia area would warn the public to be more health conscious, and physicians would administer medications cautiously. The gradual growth of MDR pathogenic microorganisms needs immediate attention, and the discovery of effective medications must take precedence. Supplementary information: The online version contains supplementary material available at 10.1007/s11756-022-01299-x.

Inhibition of biofilm formation, quorum sensing and other virulence factors in Pseudomonas aeruginosa by polyphenols of Gynura procumbens leaves.

Quorum sensing (QS) enables virulence factors in bacteria for biofilm formation and pathogenic invasion. Therefore, quorum quenching (QQ), disruption of QS circuit, becomes an alternative antimicrobial therapy. In this study, leaf extract of Gynura procumbens (GP) was used to inhibit biofilm and virulent factors in Pseudomonas aeruginosa. The extract inhibited the biofilm production (p ≤ 0.05) in P. aeruginosa strains MZ2F and MZ4A. The minimum biofilm eradication concentration (MBEC) was recorded at 250 and 500 µg/ml while total activity was found at 288 and 144 ml/g, respectively. Moreover, a significant reduction of virulence factors (p ≤ 0.05) at sub-MBEC without affecting the growth implies the QQ action of the extract. The bioactive fractions were rich in polyphenols and tentatively identified as quercetin and myricetin (Rf=0.53-0.60). Furthermore, we employed computational methods to validate our findings and their interactions with QS receptors (LasR and RhlR). Interestingly, docking studies have also shown that quercetin and myricetin are the promising anti-QS agents out of 31 GP compounds. Notably, their binding affinity ranged between -9.77 and -10.52 kcal/mol for both QS receptors, with controls ranging from -5.40 to -8.97 kcal/mol. Besides, ΔG of quercetin and myricetin with LasR was -71.56 and -74.88 kcal/mol, respectively. Moreover, compounds were suitable drug candidates with stable binding interactions. Therefore, the anti-QS activity of GP leaves and the identified polyphenols can be used in developing QQ-based therapeutics. Communicated by Ramaswamy H. Sarma.

Mycoremediation of reactive red HE7B dye by Aspergillus salinarus isolated from textile effluents.

Reactive dyes are widely utilized in the textile industry due to their advantageous properties of vivid color, water-fastness, and simple application procedures with minimal energy usage. The toxicity of most azo dyes is a significant environmental concern, as effluents from dye processing and manufacturing sectors are known to be carcinogenic and mutagenic to numerous species. These issues are more grievous in Bangladesh, one of the largest exporters of apparel. This study aimed to isolate and identify potential fungal strains from textile effluent that are capable of degrading Reactive Red HE7B dye (a sulphonated reactive azo dye), a widely used dye in local thread dyeing industries. Dye degradation assay was performed in potato dextrose broth supplemented with 50 mg/l Reactive Red HE7B and the degradation rate was measured by a UV spectrophotometer. DNA extraction, quantification, PCR, internal transcribed spacer (ITS) sequencing, and phylogenetic analysis were performed to identify the selected fungi. Among the isolates, the three best performing strains TEF -3, TEF -4, and TEF -5 showed 97.41%, 93.12%, and 82.89% dye degrading efficacy after 96 h of incubation, respectively. All three strains, TEF-3, TEF-4, and TEF-5 showed similarity with Aspergillus salinarus (accession no. NR_157473.1) and the similarity percentages were 97.02, 96.95, and 95.28 respectively. Interestingly, this study probably the very first indication of textile dye degradation by Aspergillus salinarus strains. Thus, these fungal strains possess the prospectiveness to be utilized in the textile wastewater treatment plants, since the isolates demonstrated the substantial capacity (>80%) to degrade Reactive Red dye after 96 h of incubation.

Comparative proteomic analysis to annotate the structural and functional association of the hypothetical proteins of S. maltophilia k279a and predict potential T and B cell targets for vaccination.

Stenotrophomonas maltophilia is a multidrug-resistant bacterium with no precise clinical treatment. This bacterium can be a vital cause for death and different organ failures in immune-compromised, immune-competent, and long-time hospitalized patients. Extensive quorum sensing capability has become a challenge to develop new drugs against this pathogen. Moreover, the organism possesses about 789 proteins which function, structure, and pathogenesis remain obscured. In this piece of work, we tried to enlighten the aforementioned sectors using highly reliable bioinformatics tools validated by the scientific community. At first, the whole proteome sequence of the organism was retrieved and stored. Then we separated the hypothetical proteins and searched for the conserved domain with a high confidence level and multi-server validation, which resulted in 24 such proteins. Furthermore, all of their physical and chemical characterizations were performed, such as theoretical isoelectric point, molecular weight, GRAVY value, and many more. Besides, the subcellular localization, protein-protein interactions, functional motifs, 3D structures, antigenicity, and virulence factors were also evaluated. As an extension of this work, 'RTFAMSSER' and 'PAAPQPSAS' were predicted as potential T and B cell epitopes, respectively. We hope our findings will help in better understating the pathogenesis and smoothen the way to the cure.

Community-acquired pneumonia: aetiology, antibiotic resistance and prospects of phage therapy.

Bacteria are the most common aetiological agents of community-acquired pneumonia (CAP) and use a variety of mechanisms to evade the host immune system. With the emerging antibiotic resistance, CAP-causing bacteria have now become resistant to most antibiotics. Consequently, significant morbimortality is attributed to CAP despite their varying rates depending on the clinical setting in which the patients being treated. Therefore, there is a pressing need for a safe and effective alternative or supplement to conventional antibiotics. Bacteriophages could be a ray of hope as they are specific in killing their host bacteria. Several bacteriophages had been identified that can efficiently parasitize bacteria related to CAP infection and have shown a promising protective effect. Thus, bacteriophages have shown immense possibilities against CAP inflicted by multidrug-resistant bacteria. This review provides an overview of common antibiotic-resistant CAP bacteria with a comprehensive summarization of the promising bacteriophage candidates for prospective phage therapy.