Biology subjects

Hashem, A.

Publications and source records attributed to Hashem, A..

10 recordsLinked to original sources

bioRxiv2025

FGL-1 binding to LAG-3 inhibits T cell activation via disruption of CD28 and TCR signaling

Lymphocyte-activation gene 3 (LAG-3) is known to suppress T cell receptor (TCR) signaling by disrupting CD4/CD8 coreceptor and Lck association in the absence of ligand binding. However, the impact of Fibrinogen-like protein 1 (FGL-1) binding in modulating LAG-3 mediated inhibition and its specific impact on CD28 costimulatory signaling remains unclear. This study investigates the role of LAG-3/FGL-1 interaction in modulating T cell activation. Using phosphoproteomics and confocal microscopy in LAG-3+ Jurkat cells, we demonstrated that LAG-3/FGL-1 interaction suppresses T cell activation by disrupting CD28-mediated recruitment of Lck, impairing its colocalization with CD28. Importantly, this inhibition occurs independently of CD4-bound Lck, indicating that LAG-3 ligand engagement targets both free and membrane-associated Lck pools. Consequently, this leads to suppressed phosphorylation of CD28 and TCR/CD3 signaling components, broadly attenuating downstream tyrosine phosphorylation and T cell effector functions. Our findings identify the CD28-Lck axis as a critical target of LAG-3/FGL-1 inhibitory pathway and provide a rationale for therapeutic strategies that reinvigorate CD28-Lck signaling to enhance anti-tumor immunity.

immunology↗

bioRxiv2024

Exploration of the Metabolic Potential of the Corallococcus Genus: A Rich Source of Secondary Metabolites, and CAZymes

Different secondary metabolites take on important roles. They can also transport metals, function as sexual hormones, facilitate harmonious coexistence of microbes and living beings, and induce differentiation, besides being used as competitive weapons against other bacteria, fungi, amoebae, plants, insects, and large animals. Progress in next-generation sequencing methods, together with microbial genome sequencing, has unveiled a wealth of natural products (NPs) with yet-untapped potential. Genome mining of Corallococcus species and C. exiguus subspecies that can make secondary metabolites that are clinically important has not been studied very much. The goal of this study is to look into Corallococcus genomes biosynthetic gene clusters (BGCs) and carbohydrate-active enzyme gene clusters. We fully characterize BGCs from Corallococcus reference genome sequences that are publicly available using bioinformatic tools in addition to phylogenetic and genomic comparisons. Our results show that there is a huge range of BGCs in different Corallococcus genomes, but the species or subspecies level affects the ability to make NPs. Additionally, we investigated unknown and less comparable BGCs at the species level and found that C. llansteffanensis has more potential as a reservoir of new secondary metabolites. These insights will pave the way for the algorithmic identification of species- and subspecies-specific pathways for NP development.

bioinformatics↗

bioRxiv2024

A Comprehensive Pangenome Approach to Exploring the Probiotic Potential of Weissella Confusa

BackgroundFermented foods harbour the bacterium Weissella confusa, which has probiotic properties but can potentially act as an opportunistic pathogen in humans and animals. Using pangenome analysis, our study aimed to improve the classification and identify functional traits of publicly available W. confusa genomes, focusing on evaluating their potential as probiotics. MethodThe genomic sequence of 120 strains of W. confusa was acquired from the NCBI RefSeq database. The downloaded sequences underwent a quality verification and filtering process. Ultimately, the chosen genomes were examined for comparative genomic analysis. We employed Roary to investigate the pangenome of W. confusa. Fishers exact test was utilised to analyse contingency tables, with a significance threshold of p < 0.05 (two-tailed). ResultsOur investigation revealed that the pangenome of W. confusa comprises 1100 core genes, 184 soft-core genes, 1407 shell genes, and 7006 cloud genes. This finding emphasises the "open" aspect of the W. confusa pangenome. The comparison of genomes showed that there were no acquired antibiotic resistance genes. However, the strains had different amounts of prophage regions, CRISPR arrays, and plasmids. Our research identified probiotic marker genes (PMGs), with the majority (78%) found in the core and soft-core genomes of various strains of W. confusa. ConclusionsAn extensive investigation of the W. confusa pangenome has concluded that it could be useful as a probiotic. Additional research is necessary to thoroughly evaluate the potential risks.

bioinformatics↗

bioRxiv2023

Unraveling Coinfection Dynamics into 100 Whole Genome of Diarrheal Pathogens: A Genome-to-Systems Biology Approach with Plesiomonas shigelloides

Diarrhea is the second leading cause of mortality among infants under the age of five. One of the main causes of this disease is multipathogenic infections, which can make the conditions of patients even worse. Plesiomonas shigelloides (P. shigelloides) is one of the pathogenic bacteria that contributes to the pathophysiology of diarrhea and may be implicated in coinfection with other diarrheal pathogens. Therefore, the purpose of this study is to investigate the hypothetical proteins to explore the genetic insights of P. shigelloides and its relationships with common diarrheal diseases. For this reason, we used 16S rRNA sequencing together with several biochemical tests to identify the bacteria that we isolated from diarrheal patients (8 years). Afterwards, the whole genome of P. shigelloides was sequenced, assembled and annotated in order to obtain the genomic insights of P. shigelloides. In addition, the common virulence genes of ten (10) common diarrhea-causing bacteria were identified from 100 whole genome sequences. Finally, the system biology approach was applied to predict the coinfection pattern between P. shigelloides and the virulence genes of 10 bacteria. The complete genome sequencing analysis of this bacterium revealed 899 hypothetical proteins from which 33 hypothetical proteins shared the clusters with the 109 virulence genes of 10 distinct diarrheal pathogens, forming a strong interaction based on biological processes, molecular functions, subcellular localization, or pathways. All diarrhea causing bacteria were found to have P. shigelloides microbial interactions; however, V. cholerae exhibited the strongest relationships, while C. difficile showed the weakest. The results of this investigation clearly imply that P. shigelloides shares a coinfection pattern with other bacteria that cause diarrhea. Finally, the findings from the complete genome provide new avenues for researchers to pursue their investigation of the pathophysiology of diarrhea.

systems biology↗

bioRxiv2023

Genome-Wide Exploration of the Opportunistic Providencia stuartii Unveils the Novel Genetic Interactions with the Virulence Gene of Diarrheal Pathogens

Diarrhea typically indicates an intestinal disorder, which can occur from viruses, parasites or bacterial infection. Along with the common diarrhea-causing pathogens, opportunistic bacteria may also play a role in the etiology of diarrheal disease. One of the opportunists bacteria that can cause diarrhea in both children and adults is Providencia stuartii. Therefore, the goal of this study is to explore the genetic mechanism of the opportunistic P. stuartii in microbial interactions with common diarrheal pathogens. Hence, P. stuartii was identified by utilizing the morphological observation and molecular techniques. Afterwards, the entire genome of P. stuartii was sequenced, assembled and annotated to explore the genomic insights. In addition, the virulence genes of 100 whole genome sequences from ten prevalent diarrhea-causing bacteria were identified and prioritized. Finally, the system biology approach was used to predict the protein-protein interaction network between P. stuartii and the virulence genes. The results of the present study suggests that complete genome sequencing of this bacteria contains 4011 proteins, which are crucial for this bacterium to survive. Additionally, 16 gene clusters provide 207 interacting genes that could interact with biological and molecular function, subcellular localization and pathway. The microbial interaction accompanying the virulence gene was found in all 10 diarrhea-causing bacteria except Clostridium difficile. These findings of this study could aid in the exploration of Providencia stuartii as the major causative agent of diarrhea. Additionally, the pathophysiology of diarrhea can be investigated using the microbial interactions between P. stuartii and the typical diarrheal bacteria. The results of this study may therefore be used to determine the most effective therapeutic targets for the development of medications to treat diarrhea.

genomics↗

bioRxiv2023

From Sequence to Significance: A Thorough Investigation of the Distinctive Genome Traits Uncovered in C. werkmanii strain NIB003

Citrobacter werkmanii (C. werkmanii) is an opportunistic bacterium that has received very little investigation in Bangladesh, even though it is thought to be capable of causing diseases including diarrhea and urinary tract infections. Therefore, the present study focuses on the exploration of genomic features, including antibiotic resistance genes, virulent genes, and their distinctive nature in the pathogenesis of diseases. A complete genome was sequenced for the first time in Bangladesh after the morphological, biochemical and molecular identification of this bacteria. A total of 47,65,861 nucleotide base pairs makes up the genome, which contains 4669 genes, and many of the protein-coding genes can be classified into various ontological frameworks, including COG and KEGG pathways. Notably, C. werkmanii has the capability to have interactions with Escherichia coli, Salmonella, and Klebsiella while they possess the same domains and motifs, indicating a causal role in the development of diarrhea. Furthermore, the Bangladeshi isolate of C. werkmaii has observed genetic heterogeneity when compared to other strains of C. werkmanii: C. werkmanii FDAARGOS_616, C. werkmanii LCU-V21, and C. werkmanii BF-6. This identified genetic variation of sequenced C. werkmanii could drive the functional aberration in body homeostasis of bacteria. Later, molecular dynamics studies have proven the impact of their genetic variation on the protein structure, as indicated by the SASA, RMSD, Rg, and RMSF values. Finally, the findings of C. werkmanii from the sequenced genome might provide us with a better understanding of C. werkmanii and their possible role as opportunistic bacteria in diseases including diarrhea and urinary tract infections.

genomics↗

bioRxiv2023

Genome Mining of Salinispora Uncovers a Repertoire of Secondary Metabolites and Carbohydrate-Active Enzymes

Natural products derived from microorganisms are a significant part of the pharmaceutical industrys arsenal today. These efforts have increasingly centred on marine microbes, which have produced a variety of intriguing novel chemicals. Marine-derived strains are likely candidates for natural product discovery since actinomycetes are a significant source of microbially produced natural compounds. The availability of microbial genome sequencing has revealed a number of natural products (NPs) that have not yet been thoroughly investigated. The genome mining potential of the genus Salinispora, which has potential for the production of secondary metabolites of clinical importance, remains unexplored. In this study, we have demonstrated a thorough comprehension of the genetic characteristics, biosynthetic gene clusters (BGCs), and genetic clusters for carbohydrate-active enzymes found in the Salinispora genomes. In our analysis, we have identified 686 BGCs, among which 3.79% are identical to the BGCs that produce ketomemicin B3/ketomemicin B4, salinilactam, lymphostin/neolymphostinol B/lymphostinol/neolymphostin B, benzastatin, and thiolactomycin. We have found 19.5% of the BGCs, which are only present in the genomes of Salinispora and may open the door to the development of novel drugs. We have also found a total of 3604 genes in 62 various categories of the six major carbohydrate-active enzymes. The development of new-generation bioactive compounds that are significant for biotechnology relies heavily on the scientific insights provided by genome mining in this genus.

bioinformatics↗

bioRxiv2021

Essential oil composition of Callistemon citrinus (Curtis) and its protective assessment towards Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae)

Essential oil (EO) was extracted from Callistemon citrinus leaves by hydro-distillation. The extracted oil was analysed by GC and Mass Spectroscopy. Analysis report showed that the major constituent of the essential oil was eucalyptol (40.44%). The EO of C. citrinus exhibited 100% fumigation toxicity (adult mortality) against adult and 95.8% larvicidal activity against Tribolium castaneum at 160 L/L (12 hrs) and 320 L/L (48 hrs), respectively. The effective concentration of 37.05 L/L (adult) and 144.31 L/L (larva) at 24 and 48 hrs respectively. A 100% repellent activity was observed at 20 l for adult beetles and 93.3% for larvae of T. castaneum at 20 l after 24 h. Exposure to C. citrinus EO significantly reduced beetle fecundity, ovicidal activity, egg hatching, larvae survival, and emergence of adult. The effect of EO on detoxification enzymes of T. castaneum adults was examined. Results indicated that the activity of detoxification enzymes drastically varied when compared with control. This EO had toxicant effects on all stages of the life of T. castaneum. Hence it may be used as fumigant instead of the use of using synthetic chemical fumigants.

zoology↗

bioRxiv2019

Genomics, Molecular and Evolutionary Perspective of NAC Transcription Factors

NAC (NAM, ATAF1,2, and CUC2) transcription factors are one of the largest transcription factor families found in plants and are involved in diverse developmental and signalling events. Despite the availability of comprehensive genomic information from diverse plant species, the basic genomic, biochemical, and evolutionary details of NAC TFs have not been established. Therefore, NAC TFs family proteins from 160 plant species were analyzed in the current study. The analysis, among other things, identified the first algal NAC TF in the Charophyte, Klebsormidium flaccidum. Furthermore, our analysis revealed that NAC TFs are membrane bound and contain monopartite, bipartite, and multipartite nuclear localization signals. NAC TFs were also found to encode a novel chimeric protein domain and are part of a complex interactome network. Synonymous codon usage is absent in NAC TFs and it appears that they have evolved from orthologous ancestors and undergone significant duplication events to give rise to paralogous NAC TFs.

genomics↗

bioRxiv2019

The Molecular Mass and Isoelectric Point of Plant Proteomes

A proteomic analysis of proteomes from 145 plant species revealed a pI range of 1.99 (epsin) to 13.96 (hypothetical protein). The molecular mass of the plant proteins ranged from 0.54 to 2236.8 kDa. A putative Type-I polyketide synthase (22244 amino acids) in Volvox carteri was found to be the largest protein in the plant kingdom and was not found in higher plant species. Titin (806.46 kDa) and misin/midasin (730.02 kDa) were the largest proteins identified in higher plant species. The pI and molecular weight of the plant proteome exhibited a trimodal distribution. An acidic pI (56.44% of proteins) was found to be predominant over a basic pI (43.34% of proteins) and the abundance of acidic pI proteins was higher in unicellular algae species relative to multicellular higher plants. In contrast, the seaweed, Porphyra umbilicalis, possesses a higher proportion of basic pI proteins (70.09%). Plant proteomes were also found to contain the amino acid, selenocysteine (Sec), which is the first report of the presence of this amino acid in plants. Additionally, plant proteomes also possess ambiguous amino acids Xaa (unknown), Asx (asparagine or aspartic acid), Glx (glutamine or glutamic acid), and Xle (leucine or isoleucine) as well.

plant biology↗