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Biology subjects

Islam, M. A.

Publications and source records attributed to Islam, M. A..

18 recordsLinked to original sources

Development of a Pan-Proteome Multi-Epitope Vaccine Candidate Against Nipah Virus Using Reverse Vaccinology and Immunoinformatics Approaches

Nipah virus (NiV) is a high-consequence zoonotic pathogen for which no licensed human vaccine is currently available. This study applied a consensus-guided pan-proteome immunoinformatics framework to design and prioritize a multi-epitope vaccine candidate using sequence information from all nine NiV proteins. A total of 901 NiV protein sequences were retrieved, of which 842 passed quality filtering and were processed through clustering, multiple-sequence alignment, and protein-specific consensus generation. Consensus-derived fragments were screened for cytotoxic T-lymphocyte, helper T-lymphocyte, and B-cell epitopes, followed by multi-criterion filtering based on antigenicity, allergenicity, toxicity, conservancy, class-specific immune-response properties, and human-proteome similarity. Ten epitope-selection strategies were combined with two adjuvant candidates and three construct architectures to generate 60 vaccine constructs. Shortlisted candidates were subsequently evaluated for physicochemical properties, HLA population coverage, structural characteristics, conformational B-cell epitopes, TLR3 docking, molecular dynamics, immune-response simulation, and expression-oriented optimization. VC033_V6_BD_L03 construct was prioritized as the lead candidate and showed combined predicted population coverage of 99.78% worldwide and 99.96% in South Asia. Docking against human TLR3 structure 1ZIW yielded a ClusPro score of -1624.8. During a 100-ns molecular-dynamics simulation, the complex underwent early conformational reorganization followed by lower late-phase structural variation and persistent interchain hydrogen bonding. MM/GBSA analysis yielded a mean interaction-energy estimate of -20.52, 15.42 kcal/mol. C-ImmSim predicted coordinated humoral and cellular responses, while codon optimization generated a 1,539-bp expression sequence compatible with virtual cloning into pET-28a(+). These analyses prioritize VC033_V6_BD_L03 as a consensus-derived, pan-proteome NiV multi-epitope vaccine candidate for experimental evaluation of expression, immunogenicity, safety, and protective efficacy.

bioinformatics↗

Phenotypic and Molecular Characterization of Potentially New Shigella boydii Serotype in Bangladesh

Objective: Shigella is a major cause of bacillary dysentery among children under 5 years of age, especially in low- and middle-income countries. At Dhaka hospital of icddr,b, every year around 3% of Shigella isolates from patients with diarrhea are identified as Shigella-like organisms (SLOs). These isolates do not react with any of the existing and provisional Shigella antisera. The major aims of the present study were to characterize a unique cluster of SLOs using phenotypic and genotypic methods. Methods: A cluster of 6 SLOs was characterized using biochemical tests, serotyping, antimicrobial susceptibility, and virulence assay by using the Sereny test, PCR and compared their pulsed-field gel electrophoresis (PFGE) patterns with known serotypes of Shigella spp. Antisera against the isolate were raised in a rabbit model to determine cross-reactivity with known serotypes. Results: All six SLOs were mannitol fermenting, have invasive properties, positive for ipaH and Shigella enterotoxin 2 gene along with possession of virulence plasmid of ~ 140 MDa. All isolates were resistant to ampicillin, tetracycline, sulfamethoxazole-trimethoprim, but were sensitive to mecillinam, nalidixic acid, and ciprofloxacin. Plasmid and PFGE profiles showed that the genomic patterns of these isolates were identical but were different from all other S. boydii serotypes. Antiserum prepared against one of the isolates agglutinated with all isolates but did not cross-react with other Shigella and E. coli reference strains. Conclusion: This unique cluster of isolates might belong to a new provisional serovar of S. boydii and further analysis is required to incorporate it into the stereotypic scheme of Shigella.

microbiology↗

Enhancing Germination and Assessing the Longevity of Native Plants' Seeds with Dormancy through Different Priming Techniques

Vachellia pachyceras and Convolvulus oxyphyllus are native species of arid and semi-arid desert regions, including Kuwait. They are inherently adapted to extreme conditions characterized by high temperature, prolonged drought and limited rainfall. They contribute significantly, to restore the ecosystem by providing food and shelter for wildlife. Despite their ecological importance, seed germination in both species is constrained by dormancy, and natural recruitment of seedlings is limited by narrow and unpredictable rainfall windows, severely restricting opportunities for establishment. In this context, seed priming is an effective pre-sowing technique that enables uniform and rapid germination within the short window of favorable conditions. This study aims to identify the optimal seed-priming techniques for these two keystone native species and to assess the effect of priming on seed longevity. The seeds were scarified to remove the physical dormancy prior to priming treatments. Relative seed longevity was measured for primed seeds through artificial ageing and analyzed using probit analysis and analysis of variance. Results showed that hormonal priming [(mechanical scarification + 100 ppm gibberellic acid (GA3)] for six hours and hydropriming (mechanical scarification + soaking in water) for 8 hours (h) were effective treatments among the tested priming treatments for V. pachyceras. The estimated p50 value (i.e., number of days to lose seed viability to 50%) was 22 days for hormonal priming and 21 days for hydropriming. Mechanical scarification followed by one and half hour of hydropriming was the most effective in C. oxyphyllus (p50 = 74 days). Based on these results, the longevity of V. pachyceras and C. oxyphyllus could be considered medium. Further studies are needed to determine the effectiveness of seed priming on additional ecologically and economically important native species to achieve success in revegetation programs.

ecology↗

Enhancing Carbon Conversion Efficiency and Product Yield Through Systematic Biocatalyst Design for Microbial Electrosynthesis

The unprecedented rise in greenhouse gases such as carbon dioxide (CO2), and their detrimental effects on the atmosphere have intensified the current climate emergency. This challenge has inspired the development of novel carbon capture and utilisation (CCU) technologies, specifically microbial electrosynthesis (MES), for the bioelectrochemical fixation of CO2 into commodity chemical compounds (CCCs) using microbial biocatalysts. In this study, we systematically enriched and maintained robust mixed microbial communities of electroactive bacteria (EAB) from wastewater treatment sludge to serve as biocatalysts for MES. The MES performance of these biocatalysts under different operational conditions in bioelectrochemical systems (BES) reactors were investigated. BES reactors with enriched biocatalysts incubated and maintained under controlled conditions produced higher CCCs yields than those developed at ambient temperatures, while strict anaerobic operations further improved the MES efficiency compared to aerobic conditions. At an applied potential of -1000 mV vs Ag/AgCl, CO2 conversion reached up to 88.11%, significantly outperforming the lower potential (-600 mV) operation. These findings underscore the importance of systematic development of robust and stable biocatalysts, as well as maintaining strict anaerobic conditions, for achieving efficient MES performance, thereby demonstrating the potential of our approach for scalable industrial CCU applications.

microbiology↗

The miR-221-5p/RAD18/RAD51 axis regulates DNA damage tolerance and homologous recombination to drive platinum resistance in ovarian cancer.

Platinum resistance remains a major barrier in Ovarian cancer (OC) treatment[1]. While hyperactivation of DNA damage response (DDR) is a hallmark of chemoresistance[2], the underlying epigenetic mechanisms driving this adaptation remain poorly understood. Here, we identify a novel post-transcriptional regulatory axis involving miR-221-5p that governs two critical DDR effectors: RAD18, which mediates DNA damage tolerance through trans-lesion synthesis (TLS)[3][4], and RAD51, the central recombinase for homologous recombination (HR)[5][6]. Although the miR-221/222 cluster is traditionally categorized as oncogenic[7][8], we demonstrate that the miR-221-5p arm functions as a potent tumor suppressor in OC. Bioinformatic and luciferase reporter assays confirmed that miR-221-5p directly targets the 3'UTRs of both RAD18 and RAD51. In OC clinical specimens and cell lines, miR-221-5p downregulation inversely correlates with RAD18/RAD51 expression. Functionally, miR-221-5p restoration suppressed platinum-induced PCNA mono-ubiquitination and HR, inducing a "functional BRCAness" that sensitized both established and patient-derived primary OC cells to carboplatin and PARP inhibition. Furthermore, in vivo disseminated xenograft models demonstrated that stable miR-221-5p expression significantly reduced tumor burden. Collectively, our results delineate a novel regulatory mechanism where loss of miR-221-5p drives chemoresistance by derepressing the RAD18/RAD51 axis, identifying this axis as a promising therapeutic target.

cancer biology↗

Antimicrobial resistance, pathogenicity and virulence patterns of Escherichia coli isolated from cockroaches (Blattella germanica) across diverse environments: a public health concern

This investigation explores the prevalence and antimicrobial resistance (AMR) of Escherichia coli isolated from Blattella germanica (cockroaches) from diverse locations, including homes, kitchens, and laboratories, over the course of six months, from August 2022 to January 2023. A total of 125 cockroaches were analyzed, yielding 67 (53%) of positive E. coli isolates, with kitchen environments having the highest incidence (57.77%). The existence of virulence genes (stx1, stx2, and rfbO157) was confirmed by pathogenicity assessments carried out on mouse model, which led to a considerable increase in morbidity and mortality. 82.08% of isolates showed evidence of resistance to at least one antibiotic, according to the antimicrobial susceptibility test with {beta}-lactams displaying the highest rates of resistance. Remarkably, complex resistance patterns were observed in 77.61% of the isolates, which were categorized as multidrug-resistant. Multiple antibiotic resistance genes (ARGs) were found by molecular analysis, particularly blaTEM and tetA as well as virulence-associated genes (VAGs) linked to extraintestinal pathogenic E. coli. Phylogenetic grouping indicated that 90.38% of the MDR isolates belonged to virulent groups B2 and D. These findings highlight the role of cockroaches as potential reservoirs for pathogenic E. coli, raising significant public health concerns regarding AMR. The study underscores the imperative need for thorough investigation and feasible control strategies to ease the dissemination of AMR in diverse contexts.

microbiology↗

Agent-based modeling reveals impacts of cell adhesion and matrix remodeling on cancer collective cell migration phenotypes

Understanding the phenotypic transitions of cancer cells is crucial for elucidating tumor progression mechanisms, particularly the transition from a non-invasive spheroid phenotype to an invasive network phenotype. We developed an agent-based model (ABM) using Compucell3D, an open-source biological simulation software, to investigate how varying biophysical and biochemical parameters influence emerging properties of cellular communities, including cell growth, division, and migration. Our focus was on cell-cell contact adhesion and matrix remodeling effects on cancer cell migration. We simplified enzymatic remodeling of the extracellular matrix and the subsequent enhancements to cellular chemotaxis or durotaxis as a combined effect of localized cellular secretion of a chemoattractant. By varying the chemoattractant secretion rate and contact adhesion energy, we simulated their effects on cellular behavior and driving the transition from a spheroid phenotype to a network phenotype. The model serves as a digital twin for 3D cancer cell culture, simulating cancer cell growth, division, and invasion over 1 week, validated against published data. The simulations track the emergent morphological and collective phenotype changes using key metrics such as cell circularity and invasion. Our findings indicate that increased chemoattractant secretion enhances the invasiveness of the collective cells, promoting the transition to a network phenotype. Additionally, changing cell-cell contact energy from a strong cell-cell adhesion to a weak cell-cell adhesion affects the compactness of the spheroids, resulting in lower circularity and increased collective cell invasion. Our work advances the understanding of tumor progression by providing insights into the biophysical mechanisms behind invasive cancer cell phenotypic transitions.

biophysics↗

Mathematical Modeling of Estrogen-Mediated Inflammation in the Gut and Immune System

Postmenopausal osteoporosis is a chronic inflammatory disease characterized by decreased bone mass and increased bone fracture risk. Estrogen deficiency during menopause plays a major role in post-menopausal osteoporosis by influencing bone, immune, and gut cell activity. In the gut, estrogen loss decreases tight junction proteins that bind epithelial cells of the intestinal barrier together. This increases gut permeability and alters the balance of T cells, increasing inflammatory T helper (Th17) cells and decreasing anti-inflammatory regulatory T cells (Tregs). Prebiotic dietary fibers are a promising treatment modality for gut-mediated inflammation and bone loss associated with estrogen deficiency. In a previous study, we investigated the effect of butyrate (a prebiotic by-product) on Treg levels in the gut, blood, and bone starting with healthy conditions. However, a gap remains in our mechanistic understanding of how estrogen affects systemic inflammation separately and in combination with prebiotic fibers. We developed a two-compartment dynamic model of estrogen in the gut and immune system to investigate the mechanisms of gut-mediated inflammation induced by estrogen-deficient conditions. Our initial model contains ODEs for estrogen, naive T cells, Tregs, and Th17 cells in gut and blood compartments. Estrogen is modeled using physiological mass balance equations considering its production, migration, and elimination. We integrate our estrogen model with an adapted version of our previous butyrate model, adding a population balance for Th17 cells and terms for bidirectional migration of Tregs and Th17 cells. Estrogen interactions with cells are modeled using Hill-type activation and inhibition functions. Our mathematical model predicts changes in T cell dynamics associated with changes in endogenous estrogen levels. We compare our predictions to in vivo results of estrogen, Tregs, and Th17 levels in the gut and blood after surgical menopause in mice. In the future, we will leverage this model to investigate whether the effect of prebiotic fiber treatment on estrogen-deficient bone loss is significantly affected by gut-mediated inflammation. The emphasis in this preprint is on the methods, particularly those for literature-based model parameterization.

systems biology↗

Study of Plasma Adiponectin Levels in Patients with Metabolic Syndrome and Therapeutic Indication in Bangladesh

BackgroundThe metabolic syndrome (Met-S) is a cluster of some interrelated common clinical disorders, including central obesity, dyslipidemia, hypertension, and glucose intolerance. Central obesity, accompanied by insulin resistance, is a key factor for the development of metabolic syndrome. Adiponectin is an adipose-specific plasma protein, secreted from adipocyte with anti-atherogenic and insulin-sensitizing activities. PurposeThis study aimed to investigate the relationship of plasma adiponectin levels with metabolic syndrome, related disorders and its drug repurposing through in silico approach. Materials and MethodsFor this study, 269 individuals were recruited with written consent. The participants were selected based on their full medical history, clinical examination, and laboratory reports. Anthropometric measurements as well as blood pressure was measured before sample collection. Fasting blood samples were collected for the estimation of lipid profile, blood glucose, and serum adiponectin levels. ResultsOur results show that the adiponectin levels in the subjects with Met-S were significantly lower than those of without Met-S (p <0.0001). Among the metabolic syndrome risk factors, adiponectin levels were associated with hypertriglyceridemia and reduced HDL-cholesterol (p<0.0001). Three drugs (Saquinavir, Candesartan and Glimepiride) were suggested to control the plasma adiponectin level in the subjects with Met-S. ConclusionsSince the plasma adiponectin levels are significantly lower in patients with Met-S, it might be used as diagnostic & prognostic marker for Met-S disorder and adiponectin targeted drugs might be minimize the Met-S of the subjects.

biochemistry↗

Astrocytic connection to engram neurons increased after learning

Astrocytes directly participate in learning and memory. However, the structural association between astrocytes and memory-encoding engram neurons after learning remains to be elucidated. We developed astrocyte-enhanced green fluorescent protein reconstitution across synaptic partners (eGRASP) to examine tripartite synapses between astrocytes and engram neurons. Using astrocyte-eGRASP, we found that astrocytes had increased connections to engram neurons after learning. Dendritic spines with astrocytic contacts showed enhanced morphology. Live-cell imaging of astrocyte-eGRASP revealed that astrocytic connections are stabilized by neuronal activity. These results indicate that astrocytes distinguish contact between engram neurons and generate engram-specific contact patterns during learning.

neuroscience↗

Mathematical Modeling of Impacts of Patient Differences on COVID-19 Lung Fibrosis Outcomes

Patient-specific premorbidity, age, and sex are significant heterogeneous factors that influence the severe manifestation of lung diseases, including COVID-19 fibrosis. The renin-angiotensin system (RAS) plays a prominent role in regulating the effects of these factors. Recent evidence shows patient-specific alterations of RAS homeostasis concentrations with premorbidity and the expression level of angiotensin-converting enzyme 2 (ACE2) during COVID-19. However, conflicting evidence suggests decreases, increases, or no changes in RAS peptides after SARS-CoV-2 infection. In addition, detailed mechanisms connecting the patient-specific conditions before infection to infection-induced RAS alterations are still unknown. Here, a multiscale computational model was developed to quantify the systemic contribution of heterogeneous factors of RAS during COVID-19. Three submodels were connected--an agent-based model for in-host COVID-19 response in the lung tissue, a RAS dynamics model, and a fibrosis dynamics model to investigate the effects of patient-group-specific factors in the systemic alteration of RAS and collagen deposition in the lung. The model results indicated cell death due to inflammatory response as a major contributor to the reduction of ACE and ACE2. In contrast, there were no significant changes in ACE2 dynamics due to viral-bound internalization of ACE2. The model explained possible mechanisms for conflicting evidence of patient-group-specific changes in RAS peptides in previously published studies. Simulated results were consistent with reported RAS peptide values for SARS-CoV-2-negative and SARS-CoV-2-positive patients. RAS peptides decreased for all virtual patient groups with aging in both sexes. In contrast, large variations in the magnitude of reduction were observed between male and female virtual patients in the older and middle-aged groups. The patient-specific variations in homeostasis RAS peptide concentrations of SARS-CoV-2-negative patients also affected the dynamics of RAS during infection. The model results also showed that feedback between RAS signaling and renin dynamics could restore ANGI homeostasis concentration but failed to restore homeostasis values of RAS peptides downstream of ANGI. In addition, the results showed that ACE2 variations with age and sex significantly altered the concentrations of RAS peptides and led to collagen deposition with slight variations depending on age and sex. This model may find further applications in patient-specific calibrations of tissue models for acute and chronic lung diseases to develop personalized treatments.

systems biology↗

An agent-based modeling approach for lung fibrosis in response to COVID-19

The severity of the COVID-19 pandemic has created an emerging need to investigate the long-term effects of infection on patients. Many individuals are at risk of suffering pulmonary fibrosis due to the pathogenesis of lung injury and impairment in the healing mechanism. Fibroblasts are the central mediators of extracellular matrix (ECM) deposition during tissue regeneration, regulated by anti-inflammatory cytokines including transforming growth factor beta (TGF-{beta}). The TGF-{beta}-dependent accumulation of fibroblasts at the damaged site and excess fibrillar collagen deposition lead to fibrosis. We developed an open-source, multiscale tissue simulator to investigate the role of TGF-{beta} sources in the progression of lung fibrosis after SARS-CoV-2 exposure, intracellular viral replication, infection of epithelial cells, and host immune response. Using the model, we predicted the dynamics of fibroblasts, TGF-{beta}, and collagen deposition for 15 days post-infection in virtual lung tissue. Our results showed variation in collagen area fractions between 2% and 40% depending on the spatial behavior of the sources (stationary or mobile), the rate of activation of TGF-{beta}, and the duration of TGF-{beta} sources. We identified M2 macrophages as primary contributors to higher collagen area fraction. Our simulation results also predicted fibrotic outcomes even with lower collagen area fraction when spatially-localized latent TGF-{beta} sources were active for longer times. We validated our model by comparing simulated dynamics for TGF-{beta}, collagen area fraction, and macrophage cell population with independent experimental data from mouse models. Our results showed that partial removal of TGF-{beta} sources changed the fibrotic patterns; in the presence of persistent TGF-{beta} sources, partial removal of TGF-{beta} from the ECM significantly increased collagen area fraction due to maintenance of chemotactic gradients driving fibroblast movement. The computational findings are consistent with independent experimental and clinical observations of collagen area fractions and cell population dynamics not used in developing the model. These critical insights into the activity of TGF-{beta} sources may find applications in the current clinical trials targeting TGF-{beta} for the resolution of lung fibrosis. Author summaryCOVID-19 survivors are at risk of lung fibrosis as a long-term effect. Lung fibrosis is the excess deposition of tissue materials in the lung that hinder gas exchange and can collapse the whole organ. We identified TGF-{beta} as a critical regulator of fibrosis. We built a model to investigate the mechanisms of TGF-{beta} sources in the process of fibrosis. Our results showed spatial behavior of sources (stationary or mobile) and their activity (activation rate of TGF-{beta}, longer activation of sources) could lead to lung fibrosis. Current clinical trials for fibrosis that target TGF-{beta} need to consider TGF-{beta} sources spatial properties and activity to develop better treatment strategies.

bioengineering↗

Mathematical modeling of the effects of Wnt-10b on bone metabolism

Bone health is determined by factors including bone metabolism or remodeling. Wnt-10b alters osteoblastogenesis through pre-osteoblast proliferation and differentiation and osteoblast apoptosis rate, which collectively lead to the increase of bone density. To model this, we adapted a previously published model of bone remodeling. The resulting model for the bone compartment includes differential equations for active osteoclasts, pre-osteoblasts, osteoblasts, osteocytes, and the amount of bone present at the remodeling site. Our alterations to the original model consist of extending it past a single remodeling cycle and implementing a direct relationship to Wnt-10b. Four new parameters were estimated and validated using normalized data from mice. The model connects Wnt-10b to bone metabolism and predicts the change in trabecular bone volume caused by a change in Wnt-10b input. We find that this model predicts the expected increase in pre-osteoblasts and osteoblasts while also pointing to a decrease in osteoclasts when Wnt-10b is increased.

systems biology↗

Designing novel biochemical pathways to commodity chemicals using ReactPRED and RetroPath2.0

Commodity chemicals are high-demand chemicals, used by chemical industries to synthesise cocountless chemical products of daily use. For many of these chemicals, the main production process uses petroleum-based feedstocks. Concerns over these limited resources and their associated environmental problems, as well as mounting global pressure to reduce CO2 emissions have motivated efforts to find biochemical pathways capable of producing these chemicals. Advances in metabolic engineering have led to the development of technologies capable of designing novel biochemical pathways to commodity chemicals. Computational software tools, ReactPRED and RetroPath2.0 were utilised to design 49 novel pathways to produce benzene, phenol, and 1,2-propanediol -- all industrially important chemicals with limited biochemical knowledge. A pragmatic methodology for pathway curation was developed to analyse thousands and millions of pathways that were generated using the software. This method utilises publicly accessible biological databases, including MetaNetX, PubChem, and MetaCyc to analyse the generated outputs and assign EC numbers to the predicted reactions. The workflow described here for pathway generation and curation can be used to develop novel biochemical pathways to commodity chemicals from numerous starting compounds.

bioengineering↗

In Silico Design and Analysis of Genetic Circuit-Based Whole-Cell Biosensors for Detecting Groundwater Contaminants

Contaminants of emerging concern (CEC) such as tetracycline, erythromycin, and salicylic acid in groundwater can seriously endanger the environment and human health due to their widespread and everlasting harmful effects. Thus, continuous monitoring of various CEC concentrations in groundwater is essential to ensure the safety, security, and biodiversity of natural habitats. CECs can be detected using whole-cell biosensors for environmental surveillance and monitoring purposes, as they provide a cheaper and more robust alternative to traditional and expensive analytical techniques. In this study, various genetic circuit designs are considered to model three biosensors using the genetic design automation (GDA) software, iBioSim. The genetic circuits were designed to detect multiple CECs, including atrazine, salicylic acid, and tetracycline simultaneously to produce quantitative fluorescent outputs. The biosensor responses and the viability of the genetic circuit designs were further analysed using ODE-based mathematical simulations in iBioSim. The designed circuits and subsequent biosensor modelling presented here, thus, not only show the usefulness and importance of GDA tools, but also highlight their limitations and shortcomings that need to overcome in the future; thereby, providing a practical guidance for further improvement of such tools, so that they can be more effectively and routinely used in synthetic biology research.

synthetic biology↗

Epitope-Based Peptide Vaccine Against Severe Acute Respiratory Syndrome-Coronavirus-2 Nucleocapsid Protein: An in silico Approach

With an increasing fatality rate, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has emerged as a promising threat to human health worldwide. SARS-CoV-2 is a member of the Coronaviridae family, which is transmitted from animal to human and because of being contagious, further it transmitted human to human. Recently, the World Health Organization (WHO) has announced the infectious disease caused by SARS-CoV-2, which is known as coronavirus disease-2019 (COVID-2019) as a global pandemic. But, no specific medications are available for the treatment of COVID-19 so far. As a corollary, there is a need for a potential vaccine to impede the progression of the disease. Lately, it has been documented that the nucleocapsid (N) protein of SARS-CoV-2 is responsible for viral replication as well as interferes with host immune responses. We have comparatively analyzed the sequences of N protein of SARS-CoV-2 for the identification of core attributes and analyzed the ancestry through phylogenetic analysis. Subsequently, we have predicted the most immunogenic epitope for T-cell as well as B-cell. Importantly, our investigation mainly focused on major histocompatibility complex (MHC) class I potential peptides and NTASWFTAL interacted with most human leukocyte antigen (HLA) that are encoded by MHC class I molecules. Further, molecular docking analysis unveiled that NTASWFTAL possessed a greater affinity towards HLA and also available in a greater range of the population. Our study provides a consolidated base for vaccine design and we hope that this computational analysis will pave the way for designing novel vaccine candidates.

bioinformatics↗

Quantitative assessment of fecal contamination in multiple environmental sample types in urban communities in Dhaka, Bangladesh using SaniPath microbial approach

Rapid urbanization has led to a growing sanitation crisis in urban areas of Bangladesh and potential exposure to fecal contamination in the urban environment due to inadequate sanitation and poor fecal sludge management. Limited data are available on environmental fecal contamination associated with different exposure pathways in urban Dhaka. We conducted a cross-sectional study to explore the magnitude of fecal contamination in the environment in low-income, high-income, and transient/floating neighborhoods in urban Dhaka. Ten samples were collected from each of 10 environmental compartments in 10 different neighborhoods (4 low-income, 4 high-income and 2 transient/floating neighborhoods). These 1,000 samples were analyzed with the IDEXX-Quanti-Tray technique to determine most-probable-number (MPN) of E. coli. Samples of open drains (6.91 log10 MPN/100 mL), surface water (5.28 log10 MPN/100 mL), floodwater (4.60 log10 MPN/100 mL), produce (3.19 log10 MPN/serving), soil (2.29 log10 MPN/gram), and street food (1.79 log10 MPN/gram) had the highest mean log10 E. coli contamination compared to other samples. The contamination concentrations did not differ between low-income and high-income neighborhoods for shared latrine swabs, open drains, municipal water, produce, and street foodsamples. E. coli contamination were significantly higher (p <0.05) in low-income neighborhoods compared to high-income for soil (0.91 log10 MPN/gram, 95% CI, 0.39, 1.43), bathing water (0.98 log10 MPN/100 mL, 95% CI, 0.41, 1.54), non-municipal water (0.64 log10 MPN/100 mL, 95% CI, 0.24, 1.04), surface water (1.92 log10 MPN/100 mL, 95% CI, 1.44, 2.40), and floodwater (0.48 log10 MPN/100 mL, 95% CI, 0.03, 0.92) samples. E. coli contamination were significantly higher (p<0.05) in low-income neighborhoods compared to transient/floating neighborhoods for drain water, bathing water, non-municipal water and surface water. Future studies should examine behavior that brings people into contact with the environment and assess the extent of exposure to fecal contamination in the environment through multiple pathways and associated risks.

microbiology↗

Sustained dechlorination of vinyl chloride to ethene in Dehalococcoides-enriched cultures grown without addition of exogenous vitamins and at low pH

Trichloroethene (TCE) is a ubiquitous groundwater pollutant. Successful TCE bioremediation has been demonstrated at field sites using specialized microbial consortia harboring TCE-respiring Dehaloccocoides whose growth is cobalamin (vitamin B12)-dependent. Bioaugmentation cultures grown ex situ with ample exogenous vitamins in the medium and at neutral pH may become vitamin-limited or inhibited by acidic pH once injected into field sites, resulting in incomplete TCE dechlorination and accumulation of more toxic vinyl chloride (VC). Here, we report growth of the Dehalococcoides-containing bioaugmentation culture KB-1 in a TCE-amended mineral medium devoid of vitamins and in a VC-amended mineral medium at low pH (6.0 and 5.5). In cultures grown without exogenous vitamins or cobalamin, Acetobacterium, which can synthesize 5,6-dimethylbenzimidazole (DMB), the lower ligand of cobalamin, and Sporomusa are the dominant acetogens. At neutral pH, a growing Acetobacterium population supports complete TCE dechlorination by Dehalococcoides at millimolar levels with a substantial increase in the amount of measured cobalamin (~20-fold). Sustained dechlorination of VC to ethene was achieved at a pH as low as 5.5, yet at low pH Acetobacterium is less abundant, potentially affecting the production of DMB and/or cobalamin. However, dechlorination activity at very low pH (< 5.0) was not stimulated by DMB supplementation, but was restored by raising pH to neutral. Assays in cell extracts revealed that vinyl chloride reductase (VcrA) activity declines significantly below pH 6.0 and is undetectable below pH 5.0. This study highlights the roles of and interplay between vitamin-producing populations and pH in microbial dechlorinating communities, and their importance for successful chlorinated ethenes bioremediation at field sites.

microbiology↗