Biology subjects

Anwar, A.

Publications and source records attributed to Anwar, A..

4 recordsLinked to original sources

bioRxiv2021

Metagenomic diagnosis and pathogenic network profile of SARS-CoV-2 in patients co-morbidly affected by type 2 diabetes

BackgroundThe mortality of COVID-19 disease is very high among males or elderly or individuals having comorbidities with obesity, cardiovascular diseases, lung infections, hypertension, and/or diabetes. Our study characterizes SARS-CoV-2 infected patients metagenomic features with or without type 2 diabetes to identify the microbial interactions associated with its fatal consequences. MethodThis study compared the baseline nasopharyngeal microbiome of SARS-CoV-2 infected diabetic and non-diabetic patients with controls adjusted with age and gender. The mNGS were performed using Ion GeneStudio S5 Series and the data were analyzed by the Vegan-package in R. ResultsAll three groups possessed significant bacterial diversity and dissimilarity indexes (p<0.05). Spearmans correlation coefficient network analysis illustrated 183 significant positive correlations and 13 negative correlations of pathogenic bacteria (r=0.6-1.0, p<0.05), and 109 positive correlations among normal-flora and probiotic bacteria (r>0.6, p<0.05). The SARS-CoV-2 diabetic group exhibited a significant increase of pathogens (p<0.05) and opportunistic pathogens (p<0.05) with a simultaneous decrease of normal-flora (p<0.05). The molecular docking analysis of Salivaricin, KLD4 (alpha), and enterocin produced by several enriched probiotic strains presented strong binding affinity with Shiga toxin, outer membrane proteins (ompA, omp33) or hemolysin. ConclusionThe dysbiosis of the bacterial community might be linked with severe consequences of COVID-19 infected diabetic patients, although few probiotic strains inhibited numerous pathogens in the same pathological niches. This study suggested that the promotion of normal-flora and probiotics through dietary changes and reduction of excessive pro-inflammatory states by preventing pathogenic environment might lead to a better outcome for those co-morbid patients.

genomics↗

bioRxiv2020

Microbiome Dynamics of Bovine Mastitis Progression and Genomic Determinants

The milk of lactating cows presents a complex ecosystem of interconnected microbial communities which can impose a significant influence on the pathophysiology of mastitis. Previously, we reported the alteration of microbiome (bacteria, archaea, virus) composition between clinical mastitis (CM) and healthy (H) milk. We hypothesized possible dynamic shifts of microbiome compositions with the progress of different pathological states of mastitis (CM, Recurrent CM; RCM, Subclinical Mastitis; SCM) determined by its favoring genomic potentials. To evaluate this hypothesis, we employed whole metagenome sequencing (WMS) in 20 milk samples (CM = 5, RCM = 6, SCM = 4, H = 5) to unravel the microbiome dynamics, interrelation, and relevant metabolic functions. PathoScope (PS) and MG-RAST (MR) analyses mapped the WMS data to 442 bacterial, 58 archaeal and 48 viral genomes with distinct variation in microbiome composition and abundances across these metagenomes (CM>H>RCM>SCM). PS analysis identified 385, 65, 80 and 144 bacterial strains in CM, RCM, SCM, and H milk, respectively, with an inclusion of 67.19% previously unreported opportunistic strains in mastitis metagenomes. Moreover, MR detected 56, 13, 9 and 46 archaeal, and 40, 24, 11 and 37 viral genera in CM, RCM, SCM and H-milk metagenomes, respectively. The CM-microbiomes had closest association with RCM-microbiomes followed by SCM, and H-microbiomes. Furthermore, we identified 333, 304, 183 and 50 virulence factors-associated genes (VFGs), and 48, 31, 11 and 6 antibiotic resistance genes (AGRs) in CM, RCM, SCM, and H-microbiomes, respectively, showing a significant correlation between the relative abundances of VFGs (p = 0.001), ARGs (p = 0.0001), and associated bacterial taxa. We also detected correlated variations in the presence and abundance of several metabolic functional genes related to bacterial colonization, proliferation, chemotaxis, motility and invasion, oxidative stress, virulence and pathogenicity, phage integration and excision, biofilm-formation, and quorum-sensing to be associated with different episodes of mastitis. Therefore, profiling the dynamics of microbiome in different states of mastitis, concurrent VFGs, ARGs, and genomic functional correlations will contribute to developing microbiome-based diagnostics and therapeutics for bovine mastitis, and carries significant implications on curtailing the economic fallout from this disease.

microbiology↗

bioRxiv2020

Comprehensive annotations of the mutational spectra of SARS-CoV-2 spike protein: a fast and accurate pipeline

In order to explore nonsynonymous mutations and deletions in the spike (S) protein of SARS-CoV-2, we comprehensively analyzed 35,750 complete S protein gene sequences from across six continents and five climate zones around the world, as documented in the GISAID database as of June 24th, 2020. Through a custom Python-based pipeline for analyzing mutations, we identified 27,801 (77.77 % of spike sequences) mutated strains compared to Wuhan-Hu-1 strain. 84.40% of these strains had only single amino-acid (aa) substitution mutations, but an outlier strain from Bosnia and Herzegovina (EPI_ISL_463893) was found to possess six aa substitutions. The D614G variant of the major G clade was found to be predominant across circulating strains in all climates. We also identified 988 unique aa substitution mutations distributed across 660 positions within the spike protein, with eleven sites showing high variability - these sites had four types of aa variations at each position. Besides, 17 in-frame deletions at four major regions (three in N-terminal domain and one just downstream of the RBD) may have possible impact on attenuation. Moreover, the mutational frequency differed significantly (p= 0.003, Kruskal-Wallis test) among the SARS-CoV-2 strains worldwide. This study presents a fast and accurate pipeline for identifying nonsynonymous mutations and deletions from large dataset for any particular protein coding sequence and presents this S protein data as representative analysis. By using separate multi-sequence alignment with MAFFT, removing ambiguous sequences and in-frame stop codons, and utilizing pairwise alignment, this method can derive nonsynonymus mutations (Reference:Position:Strain). We believe this will aid in the surveillance of any proteins encoded by SARS-CoV-2, and will prove to be crucial in tracking the ever-increasing variation of many other divergent RNA viruses in the future.

evolutionary biology↗

bioRxiv2020

Targeting of atherosclerotic plaque is achieved with polymeric nanoparticles encapsulating Nrf2 activator and LDL-like nanoparticles

Atherosclerotic vascular disease is the leading cause of death world-wide with few novel therapies available in spite of the ongoing health burden. Oxidative stress is a well-established driver of atherosclerotic progression; however the clinical translation of redox-based therapies is lacking. One of the challenges facing redox-based therapies is their targeted delivery to cellular domains of redox dysregulation. In the current study we sought to develop NPs encapsulating redox-based interventions that exploit passive means of targeting to selectively accumulate in atherosclerotic plaque with the aim of enhancing the intra-plaque bioavailability of interventions. Herein we present two types of nanoparticles (NPs): (i) We have employed flash nanoprecipitation to synthesize polymeric NPs encapsulating the hydrophobic Nrf2 activator drug, CDDO-Methyl, (ii) we have generated LDL-like NPs encapsulating the anti-inflammatory compound, oleic acid (OA). Nrf2-activators are a promising class of redox-active drug molecules whereby activation of Nrf2 results in the expression of several antioxidant and cyto-protective enzymes. Moreover, local activation of Nrf2 within the atherosclerotic plaque can be athero-protective. In this study we characterize the physiochemical properties of these NPs as well as confirm in vitro association of NPs with murine macrophages. In vitro drug release of CDDO-Me from polymeric NPs was determined by Nrf2-ARE-driven GFP fluorescence. In vivo localization was assessed through immunofluorescence of histological sections as well as whole-tissue light sheet fluorescence microscopy. We show that CDDO-Me-NPs and LDL-OA-NPs selectively accumulate in atherosclerotic plaque of two widely-used murine models of atherosclerosis: ApoE-/- and LDLr-/- mice. Overall, these studies underline that targeting of atherosclerotic plaque is an effective means to enhance delivery of redox-based interventions. Future work will assess the therapeutic efficacy of intra-plaque Nrf2 activation or anti-inflammatory actions with CDDO-Me-NPs or LDL-OA-NPs, respectively.

bioengineering↗