Emergence of rare and low abundant anaerobic gut Firmicutes is associated with a significant downfall of Klebsiella in human colon cancer.

Gut bacterial dysbiosis has been linked to several gastrointestinal diseases, including deadly colorectal cancer (CRC), a leading cause of mortality in cancer patients. However, perturbation in gut bacteriome during colon cancer (CC, devoid of colorectal malignancy) remains poorly explored. Here, 16S rRNA gene amplicon sequencing was carried out for fecal DNA samples targeted to hypervariable V3-V4 region by employing MiSeq platform to explore the gut bacterial community shift in CC patients. While alpha diversity indices predicted high species richness and diversity, beta diversity showed marked gut bacterial compositional dissimilarity in CC versus healthy controls (HC, n = 10 each). We observed a significant (p < 0.05, Wilcoxon Rank-Sum test) emergence of low-abundant anaerobic taxa, including Parvimonas and Peptostreptococcus, in addition to Subdoligranulum, Coprococcus, Holdemanella, Solobacterium, Bilophila, Blautia, Dorea, Moryella and several unidentified taxa, mainly affiliated to Firmicutes, in CC patients. In addition, we also traced the emergence of putative probiotic taxon Slackia, belonging to Actinomycetota, in CC patients. The emergence of anaerobic Firmicutes in CC is accompanied by a significant (p < 0.05) decline in the Klebsiella, as determined through linear discriminant analysis effect size (LEfSe) and heat tree analyses. Shifts in core microbiome and variation in network correlation were also witnessed. Taken together, this study highlighted a significant and consistent emergence of rare anaerobic Firmicutes suggesting possible anaerobiosis driving gut microbial community shift, which could be exploited in designing diagnostic and therapeutic tools targeted to CC.

Extent of Virulence and Antibiotic Resistance Genes in Helicobacter pylori and Campylobacteria.

Helicobacter pylori, a member of the clade campylobacteria, is the leading cause of chronic gastritis and gastric cancer. Virulence and antibiotic resistance of H. pylori are of great concern to public health. However, the relationship between virulence and antibiotic resistance genes in H. pylori in relation to other campylobacteria remains unclear. Using the virulence and comprehensive antibiotic resistance databases, we explored all available 354 complete genomes of H. pylori and compared it with 90 species of campylobacteria for virulence and antibiotic resistance genes/proteins. On average, H. pylori had 129 virulence genes, highest among Helicobacter spp. and 71 antibiotic resistance genes, one of the lowest among campylobacteria. Just 2.6% of virulence genes were shared by all campylobacterial members, whereas 9.4% were unique to H. pylori. The cytotoxin-associated genes (cags) seemed to be exclusive to H. pylori. Majority of the isolates from Asia and South America were cag2-negative and many antibiotic resistance genes showed isolate-specific patterns of occurrence. Just 15 (8.8%) antibiotic resistance genes, but 103 (66%) virulence genes including 25 cags were proteomically identified in H. pylori. Arcobacterial members showed large variation in the number of antibiotic resistance genes and there was a positive relation with the genome size. Large repository of antibiotic resistance genes in campylobacteria and a unique set of virulence genes might have important implications in shaping the course of virulence and antibiotic resistance in H. pylori.

In silico identification of potential phytochemical inhibitors for mpox virus: molecular docking, MD simulation, and ADMET studies.

The mpox virus (MPXV), a member of the Poxviridae family, which recently appeared outside of the African continent has emerged as a global threat to public health. Given the scarcity of antiviral treatments for mpox disease, there is a pressing need to identify and develop new therapeutics. We investigated 5715 phytochemicals from 266 species available in IMMPAT database as potential inhibitors for six MPXV targets namely thymidylate kinase (A48R), DNA ligase (A50R), rifampicin resistance protein (D13L), palmytilated EEV membrane protein (F13L), viral core cysteine proteinase (I7L), and DNA polymerase (E9L) using molecular docking. The best-performing phytochemicals were also subjected to molecular dynamics (MD) simulations and in silico ADMET analysis. The top phytochemicals were forsythiaside for A48R, ruberythric acid for A50R, theasinensin F for D13L, theasinensin A for F13L, isocinchophyllamine for I7L, and terchebin for E9L. Interestingly, the binding energies of these potential phytochemical inhibitors were far lower than brincidofovir and tecovirimat, the standard drugs used against MPXV, hinting at better binding properties of the former. These findings may pave the way for developing new MPXV inhibitors based on natural product scaffolds. However, they must be further studied to establish their inhibitory efficacy and toxicity in in vitro and in vivo models.

Benzothiazole derivatives as p53-MDM2 inhibitors: in-silico design, ADMET predictions, molecular docking, MM-GBSA Assay, MD simulations studies.

Breast cancer stands as the most prevalent malignancy among the female populace. One of the pivotal domains in the therapeutic landscape of breast cancer revolves around the precise targeting of the p53-MDM2 inhibitory pathway. The advent of p53-MDM2 inhibition in the context of developing treatments for breast cancer marks a significant stride. In the quest for enhancing the efficacy of p53-MDM2 inhibition against breast cancer, a new series of benzothiazole compounds (B1-B30) was designed through in-silico methodologies in the present work. Using Schrodinger Maestro, the compounds underwent molecular docking assessments against the p53-MDM2 target (PDB: 4OGT). Compared to reference compounds, B25 and B12 exhibited notably elevated glide scores. Extensive in-silico studies, including ADMET and toxicity evaluations, were performed to predict pharmacokinetics, drug likeness, and toxicity. All compounds adhered to Lipinski criteria, signifying favorable oral drug properties. The MM-GBSA analysis indicated consistent binding free energies. Molecular dynamics simulations for B25 over 200 ns assessed complex stability and interactions. In summary, these compounds exhibit potential for future cancer therapy medication development.Communicated by Ramaswamy H. Sarma.

Development of novel thiazolidine-2,4-dione derivatives as PPAR-γ agonists through design, synthesis, computational docking, MD simulation, and comprehensive in vitro and in vivo evaluation.

The present study was conducted to develop new novel 2,4-thiazolidinedione derivatives (3h-3j) as peroxisome proliferator-activated receptor-γ (PPAR-γ) modulators for antidiabetic activity. The objective was to overcome the adverse effects of existing thiazolidinediones while maintaining their pharmacological benefits. The synthesized compounds were elucidated based on FT-IR, 1H-NMR, 13C-NMR, and MS techniques. Molecular docking was utilized to investigate the interaction binding modes, binding free energy, and amino acids engaged in the compounds' interactions with the target protein. Subsequently, molecular dynamics modelling was used to assess the stability of the top-docked complexes and an assay was utilized to assess the cytotoxicity of the compounds to C2C12 myoblasts. Compounds 3h-3j exhibited PPAR-γ modulatory activity and demonstrated significant hypoglycaemic effects when compared to the reference drug pioglitazone. The new compounds were evaluated for their in vivo blood glucose-lowering potential by using a dexamethasone-induced diabetic rat model. All the compounds showed a hypoglycaemic effect of 108.04 ± 4.39, 112.55 ± 6.10, and 117.48 ± 43.93, respectively, along with pioglitazone (153.93 ± 4.61) compared to the diabetic control. Additionally, all the compounds significantly reduced AST and ALT levels and did not cause liver damage.

Overexpression of a membrane transport system MSMEG_1381 and MSMEG_1382 confers multidrug resistance in Mycobacterium smegmatis.

Mycobacterium tuberculosis is a leading cause of human mortality worldwide, and the emergence of drug-resistant strains demands the discovery of new classes of antimycobacterial that can be employed in the therapeutic pipeline. Previously, a secondary metabolite, chrysomycin A, isolated from Streptomyces sp. OA161 displayed potent bactericidal activity against drug-resistant clinical isolates of M. tuberculosis and different species of mycobacteria. The antibiotic inhibits mycobacterial topoisomerase I and DNA gyrase, leading to bacterial death, but the mechanisms that could cause resistance to this antibiotic are currently unknown. To further understand the resistance mechanism, using M. smegmatis as a model, spontaneous resistance mutants were isolated and subjected to whole-genome sequencing. Mutation in a TetR family transcriptional regulator MSMEG_1380 was identified in the resistant isolates wherein the gene was adjacent to an operon encoding membrane proteins MSMEG_1381 and MSMEG_1382. Sequence analysis and modeling studies indicated that MSMEG_1381 and MSMEG_1382 are components of the Mmp family of efflux pumps and over-expression of either the operon or individual genes conferred resistance to chrysomycin A, isoniazid, and ethambutol. Our study highlights the role of membrane transporter proteins in conferring multiple drug resistance and the utility of recombinant strains overexpressing membrane transporters in the drug screening pipeline.

Functional network analysis identifies multiple virulence and antibiotic resistance targets in Stenotrophomonas maltophilia.

Stenotrophomonas maltophilia, an emerging multidrug-resistant opportunistic bacterium in humans is of major concern for immunocompromised individuals for causing pneumonia and bloodborne infections. This bacterial pathogen is associated with a considerable fatality/case ratio, with up to 100%, when presented as hemorrhagic fever. It is resistant to commonly used drugs as well as to antibiotic combinations. In-silico based functional network analysis is a key approach to get novel insights into virulence and resistance in pathogenic organisms. This study included the protein-protein interaction (PPI) network analysis of 150 specific genes identified for antibiotic resistance mechanism and virulence pathways. Eight proteins, namely, PilL, FliA, Smlt2260, Smlt2267, CheW, Smlt2318, CheZ, and FliM were identified as hub proteins. Further docking studies of 58 selected phytochemicals were performed against the identified hub proteins. Deoxytubulosine and corosolic acid were found to be potent inhibitors of hub proteins of pathogenic S. maltophilia based on protein-ligand interactive study. Further pharmacophore studies are warranted with these molecules to develop them as novel antibiotics against S. maltophilia.

Integrated molecular-network analysis reveals infertility-associated key genes and transcription factors in the non-obstructive azoospermia.

BACKGROUND: Male infertility is a multifactorial reproductive health problem with complex causes. Non-obstructive azoospermia (NOA) is characterized by failure of spermatogenesis, leading to the absence of spermatozoa in ejaculates. The molecular mechanism underlying the NOA is still not well understood. OBJECTIVES: This study aims to identify the key genes involved in male infertility that could be a potential biomarker in the diagnosis and prognosis of azoospermia. STUDY DESIGN: The microarray expression profiles dataset GSE45885 and GSE45887 were downloaded from the NCBI's Gene Expression Omnibus (GEO) database and analyzed for male infertility-associated differentially expressed genes (DEGs) using the GEO2R tool. The common DEGs between the two datasets were combined and their protein-protein interaction (PPI) network was constructed using Cytoscape to reveal the hub genes by topology and module analysis. In addition, transcription factors (TFs) and protein kinases regulating the hub genes were identified using the X2K tool. Then, the expression of the hub genes was validated by analyzing the GSE190752 microarray dataset. Further, the PPI network was screened for biological roles and enriched pathways using DAVID software. RESULTS: About 256 DEGs associated with NOA were identified and constructed the PPI network to find the infertility-associated proteins. The biological processes linked with these proteins were spermatogenesis, cell differentiation, flagellated sperm motility, and spermatid development. The topology and module analysis of the infertility-associated protein network identified the hub genes TEX38, FAM71F, PRR30, FAM166A, LYZL6, TPPP2, ARMC12, SPACA4, and FAM205A, which were found to be upregulated in the non-obstructive azoospermia. In addition, a total of 23 transcription factors and 3 protein kinases that are regulating these key hub genes were identified. Further these hub genes expression was validated using the microarray data and found that their expression was increased in the testicular biopsies obtained from NOA subjects, compared to healthy individuals. CONCLUSION: The identified key genes and its associated transcription factors are known to regulate the infertility-related processes in the non-obstructive azoospermia. Also, the clinical sample-based microarray data validation for the expression of these key hub genes indicates their potentiality to develop them as diagnostic or prognostic biomarkers for NOA.

Early diagnostic and prognostic biomarkers for gastric cancer: systems-level molecular basis of subsequent alterations in gastric mucosa from chronic atrophic gastritis to gastric cancer.

PURPOSE: It is important to comprehend how the molecular mechanisms shift when gastric cancer in its early stages (GC). We employed integrative bioinformatics approaches to locate various biological signalling pathways and molecular fingerprints to comprehend the pathophysiology of the GC. To facilitate the discovery of their possible biomarkers, a rapid diagnostic may be made, which leads to an improved diagnosis and improves the patient's prognosis. METHODS: Through protein-protein interaction networks, functional differentially expressed genes (DEGs), and pathway enrichment studies, we examined the gene expression profiles of individuals with chronic atrophic gastritis and GC. RESULTS: A total of 17 DEGs comprising 8 upregulated and 9 down-regulated genes were identified from the microarray dataset from biopsies with chronic atrophic gastritis and GC. These DEGs were primarily enriched for CDK regulation of DNA replication and mitotic M-M/G1 phase pathways, according to KEGG analysis (p > 0.05). We discovered two hub genes, MCM7 and CDC6, in the protein-protein interaction network we obtained for the 17 DEGs (expanded with increased maximum interaction with 110 nodes and 2103 edges). MCM7 was discovered to be up-regulated in GC tissues following confirmation using the GEPIA and Human Protein Atlas databases. CONCLUSION: The elevated expression of MCM7 in both chronic atrophic gastritis and GC, as shown by our comprehensive investigation, suggests that this protein may serve as a promising biomarker for the early detection of GC.

Development of microbial enrichments for simultaneous removal of sulfur and nitrogenous metabolites in saline water aquaculture.

AIM: The aim of the study was to develop microbial enrichments from the nitrifying microbial consortia and the environment for simultaneous removal of ammonia, nitrate, and sulfide in aquaculture systems at varied salinities. METHODS AND RESULTS: Sulfur and nitrogen metabolites are the major factors affecting the farmed aquatic animal species and deteriorate the receiving environments causing ecological damage. The present study reports the development of microbial enrichments from the nitrifying microbial consortia and the environment. The enrichments used thiosulfate or thiocyanate as an energy source and simultaneously removed sulfur, ammonia, and nitrite in spiked medium (125 mg/l ammonia; 145 mg/l nitrite). Further, the microbes in the enrichments could grow up to 30 g/l salinity. Metagenomic studies revealed limited microbial diversity suggesting the enrichment of highly specialized taxa, and co-occurrence network analysis showed the formation of three micro-niches with multiple interactions at different taxonomic levels. CONCLUSIONS: The ability of the enrichments to grow in both organic and inorganic medium and simultaneous removal of sulfide, ammonia, and nitrite under varied salinities suggests their potential application in sulfur, nitrogen, and organic matter-rich aquaculture pond environments and other industrial effluents.

Efficacy of HDAC inhibitors and epigenetic modulation in the amelioration of synovial inflammation, cellular invasion, and bone erosion in rheumatoid arthritis pathogenesis.

Rheumatoid arthritis (RA), an auto-immune disorder affected 1 % of the population around the globe. The pathophysiology of RA is highly concerted process including synovial hyperplasia, pannus formation, bone erosion, synovial cell infiltration in joints, and cartilage destruction. However, recent reports suggest that epigenetics play a pivotal role in the formation and organization of immune response in RA. Particularly, altered DNA methylation and impaired microRNA (miRNA) were detected in several immune cells of RA patients, such as T regulatory cells, fibroblast-like synoviocytes, and blood mononuclear cells. All these processes can be reversed by regulating the ubiquitous or tissue-based expression of histone deacetylases (HDACs) to counteract and terminate them. Hence, HDAC inhibitors (HDACi) could serve as highly potent anti-inflammatory regulators in the uniform amelioration of inflammation. Therefore, this review encompasses the information mainly focussing on the epigenetic modulation in RA pathogenesis and the efficacy of HDACi as an alternative therapeutic option for RA treatment. Overall, these studies have reported the targeting of HDAC1, 2 & 6 molecules would attenuate synoviocyte inflammation, cellular invasion, and bone erosion. Further, the inhibitors such as trichostatin A, suberoyl bis-hydroxamic acid, suberoyl anilide hydroxamic acid, and other compounds are found to attenuate synovial inflammatory immune response, clinical arthritis score, paw swelling, bone erosion, and cartilage destruction. Insight to view this, more clinical studies are required to determine the efficacy of HDACi in RA treatment and to unravel the underlying molecular mechanisms.

Inferring Recombination Events in SARS-CoV-2 Variants In Silico.

Over the last 34 months, at least 10 severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) distinct variants have evolved. Among these, some were more infectious while others were not. These variants may serve as candidates for identification of the signature sequences linked to infectivity and viral transgressions. Based on our previous hijacking and transgression hypothesis, we aimed to investigate whether SARS-CoV-2 sequences associated with infectivity and trespassing of long noncoding RNAs (lncRNAs) provide a possible recombination mechanism to drive the formation of new variants. This work involved a sequence and structure-based approach to screen SARS-CoV-2 variants in silico, taking into account effects of glycosylation and links to known lncRNAs. Taken together, the findings suggest that transgressions involving lncRNAs may be linked with changes in SARS-CoV-2-host interactions driven by glycosylation events.

Unveiling the role of hub proteins in controlling quorum sensing regulated virulence through analogues in Pseudomonas aeruginosa PAO1: A functional protein-protein network biology approach.

The protein-protein interaction (PPI) network analysis of specific genes identified for biofilm production and virulence/secretion system mediated by quorum sensing. The PPI depicted 13 hub proteins (namely rhlR, lasR, pscU, vfr, exsA, lasI, gacA, toxA, pilJ, pscC, fleQ, algR, and chpA) out of 160 nodes involving 627 edges. The PPI network analysis based on topographical features depicted pcrD with the highest degree value and vfr gene with the greatest betweenness centrality and closeness centrality (BC and CC) values. Based on in silico results, curcumin used as an Acyl homo-serine lactone (AHL) mimicker in P. aeruginosa, was also found effective in suppressing the quorum sensing regulated virulence factors such as elastase and pyocyanin. Based on in vitro experiment, curcumin suppressed biofilm formation at 62 µg/ml concentration. Host-pathogen interaction experiment showed that curcumin was also proved to be efficient in saving C. elegans from paralysis and killing effects of P. aeruginosa PAO1.

Molecular detection of monkeypox and related viruses: challenges and opportunities.

The recent widespread emergence of monkeypox (mpox), a rare and endemic zoonotic disease by monkeypox virus (MPXV), has made global headlines. While transmissibility (R0 ≈ 0.58) and fatality rate (0-3%) are low, as it causes prolonged morbidity, the World Health Organization has declared monkeypox as a public health emergency of international concern. Thus, effective containment and disease management require quick and efficient detection of MPXV. In this bioinformatic overview, we summarize the numerous molecular tests available for MPXV, and discuss the diversity of genes and primers used in the polymerase chain reaction-based detection. Over 90 primer/probe sets are used for the detection of poxviruses. While hemagglutinin and A-type inclusion protein are the most common target genes, tumor necrosis factor receptor and complement binding protein genes are frequently used for distinguishing Clade I and Clade II of MPXV. Problems and possibilities in the detection of MPXV have been discussed.

Genomic potential for exopolysaccharide production and differential polysaccharide degradation in closely related Alteromonas sp. PRIM-21 and Alteromonas fortis 1T.

Members of the genus Alteromonas are widely distributed in diverse marine environments and are often associated with marine organisms. Their ability to produce exopolysaccharides (EPS) and depolymerize sulfated algal polysaccharides has provided industrial importance to some species. Here, we describe the draft genome of an algae-associated strain namely, Alteromonas sp. PRIM-21 isolated from the southwest coast of India to understand the EPS biosynthetic pathways as well as polysaccharide depolymerization system in comparison to the closely related strain Alteromonas fortis 1T that shares 99.8% 16S rRNA gene sequence similarity. Whole-genome shotgun sequencing of Alteromonas sp. PRIM-21 yielded 50 contigs with a total length of 4,638,422 bp having 43.86% GC content. The resultant genome shared 95.9% OrthoANI value with A. fortis 1 T, and contained 4125 predicted protein-coding genes, 71 tRNA and 10 rRNA genes. Genes involved in Wzx/Wzy-, ABC transporter- and synthase-dependent pathways for EPS production and secretion were common in both Alteromonas sp. PRIM-21 and A. fortis 1T. However, the distribution of carbohydrate-active enzymes (CAZymes) was heterogeneous. The strain PRIM-21 harbored polysaccharide lyases for the degradation of alginate, ulvan, arabinogalactan and chondroitin. This was further validated from the culture-based assays using seven different polysaccharides. The depolymerizing ability of the bacteria may be useful in deriving nutrients from the biopolymers produced in the algal host while the EPS biosynthesis may provide additional advantages for life in the stressful marine environment. The results also highlight the genetic heterogeneity in terms of polysaccharide utilization among the closely related Alteromonas strains.

Prevalence and heterogeneity of antibiotic resistance genes in Orientia tsutsugamushi and other rickettsial genomes.

Despite a million infections every year and an estimated one billion people at risk, scrub typhus is regarded as a neglected tropical disease. The causative bacterium Orientia tsutsugamushi, a member of rickettsiae, seems to be intrinsically resistant to several classes of antibiotics. The emergence of antibiotic-resistant scrub typhus is likely to become a global public health concern. Yet, it is unknown as to how common antibiotic resistance genes are in O. tsutsugamushi, and how variable these loci are among the genomes of rickettsiae. By using the comprehensive antibiotic resistance database, we explored 79 complete genomes from 24 species of rickettsiae for antibiotic resistance loci. There were 244 unique antibiotic resistance genes in rickettsiae. Both the total and unique antibiotic resistance genes in O. tsutsugamushi were significantly less compared to other members of rickettsiae. However, antibiotic resistance genes in O. tsutsugamushi genomes were more unique and highly variable. Many genes such as resistant variants of evgS, and vanS A/G were present in numerous copies. These results will have important implications in the context of antibiotic-resistant scrub typhus.

Exploring breast cancer exosomes for novel biomarkers of potential diagnostic and prognostic importance.

The comprehensive bioinformatics analysis of breast cancer exosomes revealed that HSP90AA1, CCT2, and ENO1 were novel hub genes in the giant protein-protein interaction network of 110 exosomal proteins. Exosomes and their cargo such as discrete proteins, nucleic acids, and lipids are having potential role in the pathophysiology of breast cancer (BC). This study showed that the identified hub genes were particularly abundant in GO and KEGG pathways relevant to the positive regulation of telomerase. In addition, these hub genes were found to be considerably overexpressed in breast adenocarcinoma patients compared to healthy controls, and further, this overexpression is linked to the poor prognosis in BC patients. Furthermore, the ROC analysis revealed that CCT2 gene has strong diagnostic and prognostic value for BC. Additionally, this in silico analysis found that the anticancer agents and HSP90 inhibitors such as ganetespib, retaspimycin, and tanespimycin would have considerable potential in the treatment of BC. Overall, this study findings imply that HSP90AA1, a molecular chaperon and CCT2, a chaperonin would serve as diagnostic and prognostic biomarkers, respectively, for BC. However, these findings need to be further confirmed by laboratory and clinical studies for validating their potential applications. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03422-w.

Identification of key gene signatures and their characterization by expression correlation with drug sensitivity in smoking-associated oral squamous cell carcinoma.

AIMS: Oral squamous cell carcinoma (OSCC), a most frequent type of head-and-neck cancer, is becoming more common and posing a substantial health risk. Using a network biology strategy, this study intended to find and investigate critical genes associated with OSCC. MATERIALS AND METHODS: The extended protein-protein interaction networks for differentially expressed genes related to smoking and nonsmoking conditions of OSCC were constructed and visualized using Cytoscape software. The hub genes/proteins were determined based on degree and betweenness centrality measures and then evaluated and validated for expression using the Gene Expression Profiling Interactive Analysis 2 (GEPIA2), and their relationship to the sensitivity of small molecules was discovered utilizing the Gene Set Cancer Analysis (GSCA) web server. RESULTS: A total of 596 differentially expressed genes were screened, and four genes, interleukin (IL)-6, JUN, tumor necrosis factor (TNF), and vascular endothelial growth factor A (VEGFA), were identified as hub proteins, and their expression and overall survival in head-and-neck cancers were further investigated using GEPIA2. TNF and VEGFA gene expressions were considerably greater in cancers when compared to normal samples, while JUN and IL-6 gene expressions were not statistically significant. Further, these hub proteins are found to have a substantial favorable correlation with overall survival of head-and-neck cancer patients. Finally, GSCA was used to predict gene-specific potential drugs that act on these molecules by combining mRNA expression and drug sensitivity data from the Genomics of Drug Sensitivity in Cancer and the Cancer Therapeutics Response Portal. CONCLUSIONS: The hub genes/proteins identified in this study could help researchers better understand the molecular processes involved in the progression and metastasis of oral cancer in smokers.

Vanillin derivative inhibits quorum sensing and biofilm formation in Pseudomonas aeruginosa: a study in a Caenorhabditis elegans infection model.

Vanillin and its derivative, (4-((E)-(4-hydroxy-2-methylphenylimino) methyl)-2-methoxyphenol (MMP) were showed clear inhibition of violacein and pyocyanin at sub-MICs indicating a possible quorum quenching effect of both the compounds. MMP was able to inhibit the biofilm formation in Pseudomonas aeruginosa PAO1 at 125 µg/mL (p < 0.05), while vanillin at 250 µg/mL (p < 0.05) indicating that they act against quorum sensing regulated biofilm formation. The inhibition of biofilm was confirmed by visualization through fluorescence microscopy followed by docking analysis of molecules against quorum sensing activator proteins. Caenorhabditis elegans survival assay revealed that vanillin and MMP were able to increase survival of C. elegans from P. aeruginosa PAO1 infection. The study showed that the potent features of the MMP and vanillin in inhibiting the quorum sensing regulated virulence and biofilm, which was proved in C. elegans infection model as well as molecular docking studies.

Molecular Insights on the Possible Role of Annexin A2 in COVID-19 Pathogenesis and Post-Infection Complications.

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has infected >235 million people and killed over 4.8 million individuals worldwide. Although vaccines have been developed for prophylactic management, there are no clinically proven antivirals to treat the viral infection. Continuous efforts are being made all over the world to develop effective drugs but these are being delayed by periodic outbreak of mutated SARS-CoV-2 and a lack of knowledge of molecular mechanisms underlying viral pathogenesis and post-infection complications. In this regard, the involvement of Annexin A2 (AnxA2), a lipid-raft related phospholipid-binding protein, in SARS-CoV-2 attachment, internalization, and replication has been discussed. In addition to the evidence from published literature, we have performed in silico docking of viral spike glycoprotein and RNA-dependent RNA polymerase with human AnxA2 to find the molecular interactions. Overall, this review provides the molecular insights into a potential role of AnxA2 in the SARS-CoV-2 pathogenesis and post-infection complications, especially thrombosis, cytokine storm, and insulin resistance.