Biology subjects

Dinarvand, M.

Publications and source records attributed to Dinarvand, M..

5 recordsLinked to original sources

bioRxiv2025

Rapid catecholamine trafficking regulates neutrophil functions and neutrophil-platelet interactions

Neutrophils are key effector cells of the innate immune system that respond to small signaling molecules regulating immune responses. For a long time, similarities between neuronal and immune cells have been discussed. Here, we show that human neutrophils rapidly take up, package and use catecholamine neurotransmitters such as dopamine or epinephrine via the machinery known from neurons. Uptake and release of catecholamines as well as trafficking and packaging into MPO/VMAT2-positive primary vesicles is visualized with false fluorescent neurotransmitters. We also directly image the fast (> 10 s) and transient release of catecholamines from neutrophils with near infrared fluorescent nanosensors. Serotonin or activated platelets trigger calcium (Ca2+) signaling and consequently exocytosis of catecholamines. They reduce NET-formation but increase platelet aggregation. Thus, we establish similarities between neurons and neutrophils and identify a paracrine neutrophil-platelet feedback loop relevant for inflammatory and coagulatory conditions.

immunology↗

bioRxiv2022

dSeqSb: A systems biology approach to decipher dynamics of 1 host-pathogen interactions using temporal dual RNA-seq data

Infection triggers a dynamic cascade of reciprocal events between host and pathogen wherein the host activates complex mechanisms to recognise and kill pathogens while the pathogen adjusts its virulence and fitness to avoid eradication by the host. The interaction between the pathogen and the host results in large-scale changes in gene expression in both organisms. Dual RNA-seq, the simultaneous detection of host and pathogen transcripts, has become a leading approach to unravel complex molecular interactions between the host and the pathogen and is particularly informative for intracellular organisms. The amount of in vitro and in vivo dual RNA-seq data is rapidly growing which demands computational pipelines to effectively analyse such data. In particular, holistic, systems-level, and temporal analyses of dual RNA-seq data are essential to enable further insights into the host-pathogen transcriptional dynamics and potential interactions. Here, we developed an integrative network-driven bioinformatics pipeline, dRNASb, a systems biology-based computational pipeline to analyse temporal transcriptional clusters, incorporate molecular interaction networks (e.g., protein-protein interactions), identify topologically and functionally key transcripts in host and pathogen, and associate host and pathogen temporal transcriptome to decipher potential between-species interactions. The pipeline is applicable to various dual RNA-seq data from different species and experimental conditions. As a case study, we applied dRNASb to analyse temporal dual RNA-seq data of Salmonella-infected human cells, which enabled us to uncover genes contributing to the infection process and their potential functions and to identify potential host-pathogen interactions between host and pathogen genes. Overall, dRNASb has the potential to identify key genes involved in bacterial growth or host defence mechanisms for future uses as therapeutic targets.

microbiology↗

bioRxiv2021

Isolation and Genomics of multidrug-resistant Brevundimonas diminuta collected from patients with pertussis-like symptoms

Brevundinomas diminuta is known as an opportunistic pathogen and is rarely associated with invasive infections in humans causing infection in the different parts of the body. In this study, we identified three B. diminuta isolates from three patients with an initial diagnosis of pertussis. Isolates were confirmed using biochemical tests and 16s rRNA sequencing. All isolates were resistant to three different classes of antimicrobial drugs including ceftazidime and ciprofloxacin. We performed Illumina whole-genome sequencing for two isolates. The results showed an average genome size of 3.25 Mbp with the G+C content 67% with multiple predicted virulence factors and genes leading to antibiotic resistance. We found an open pan-genome with 1502 core genes by analysing 13 available global B. diminuta isolated from different environments such as water, soil, or gentamicin fermentation residue. In the phylogenetic analysis, our isolates were grouped with B. diminuta isolate collected from an oral cavity of a patient in the USA.

genomics↗

bioRxiv2020

Identification bioactive compounds from marine microorganism and exploration of structure activity relationships

Marine natural products (MNPs) have become new strong leads for antimicrobial drug discovery and an effective alternative to control drug resistant infections. Herein we report the bioassay guided fractionation of marine extracts from sponges Lendenfeldia, Ircinia and Dysidea that led us to identify novel compounds with antimicrobial properties. Tertiary amines or quaternary amine salts: anilines 1, benzylamines 2, tertiary amines 3 and 4, and quaternary amine salt 5, along with three known compounds (6-8) were isolated from a crude extract and MeOH eluent marine extracts. The absolute configurations of the new compounds were assigned based on tandem mass spectrometry (MS) analysis. Several of the compounds exhibited potent in-vitro antibacterial activity, especially against Methicillin-resistant Staphylococcus aureus (MRSA) (MICs from 15.6 to 62.5 micro g/mL). Herein, we also, report structure activity relationships of a diverse range of commercial structurally similar compounds. The structure activity relationships (SARs) results clearly demonstrate that modification of the amines through linear chain length, and inclusion of aromatic rings, modifies the observed antimicrobial activity towards different biological activity. Several commercially available compounds, which are structurally related to the molecules we discovered showed broad spectrum antimicrobial activity against different test pathogens with an MIC50 range of 50 to 0.01 microM. The results of cross-referencing antimicrobial activity and cytotoxicity establish that these compounds are promising potential lead molecules, with a favourable therapeutic index for antimicrobial drug development. Additionally, the SAR studies show that simplified analogues of the isolated compounds with increased bioactivity

microbiology↗

bioRxiv2018

Discovery of antimicrobial compounds from Lendenfeldia, Ircinia and Dysidea sponges using bioassay guided fractionation of marine extracts

Multidrug resistant bacteria have emerged as a threat to public health all over the world. At the same time, the discovery of new bioactive small molecules with antimicrobial activity and suitable pharmacological properties has waned. Herein we report the screening of marine extracts to identify novel compounds with antimicrobial activity. Bioassay guided fractionation has enabled the discovery and identification of a family of simple amines with promising activity against methicillin resistant Staphylococcus aureus (MRSA). To confirm the natural product structures proposed, these compounds and analogues have been prepared synthetically. Several of the synthetic analogues showed promising bioactivity against the medically important pathogens MRSA (MICs to 12.5 {micro}M), Mycobacterium tuberculosis (MICs to 0.02 {micro}M), uropathogenic Escherichia coli (MIC 6.2 {micro}M) and Pseudomonas aeruginosa (MIC 3.1 {micro}M). Cross-referencing antimicrobial activity and toxicity show that these synthetic compounds display a favourable therapeutic index for their target pathogens.

developmental biology↗