Biology subjects

Issa, M.

Publications and source records attributed to Issa, M..

6 recordsLinked to original sources

bioRxiv2026

ABC transporters support Drosophila intestinal stem and progenitor cells during cytotoxic challenge

Adult stem cells can survive diverse insults, from ionizing radiation to toxic chemicals. In vertebrates, ABC transporter expression and dye-efflux capacity have been associated with stem-cell protection and multidrug resistance. How compound accumulation differs between adult stem cells and their differentiated daughters within an intact tissue remains poorly understood. Here, we show that adult Drosophila intestinal stem/progenitor cells maintain a distinct low-accumulation state for membrane-permeable compounds and that ABC transporters contribute to this phenotype and to the response to cytotoxic stress. Across nine membrane-permeable probes, stem/progenitor cells accumulated eight at lower levels than differentiated enterocytes. We selected tetramethylrhodamine methyl ester (TMRM), a membrane-permeable fluorescent probe that showed a strong difference in accumulation between stem/progenitor cells and enterocytes, as a quantitative readout for an RNAi screen of all 56 Drosophila ABC-family genes. The screen identified seven candidate transporters whose depletion increased the stem/progenitor-to-enterocyte TMRM fluorescence ratio. Further characterization of one of them, ABCB7, showed that ABCB7-depleted guts contained fewer mitotic cells during cytotoxic drug exposure. These results implicate ABC transporters in lower compound accumulation in Drosophila intestinal stem/progenitor cells and support a role for ABC transporters in their response to cytotoxic challenge.

genetics↗

bioRxiv2026

A dsRNA Virus Converts Early Endosomes into Stable Replication Organelles Through Maturation Arrest and Retrograde Transport

Infectious bursal disease virus (IBDV) and infectious pancreatic necrosis virus (IPNV) are major animal pathogens that impose a heavy burden on the poultry and aquaculture industries. Yet, major aspects of their unique replication program remain unknown. IBDV is unusual among double-stranded RNA viruses in that it replicates in association with host endosomes. We previously demonstrated this association to be orchestrated by the viral protein VP3 and the early endosomal lipid phosphatidylinositol 3-phosphate [PtdIns(3)P], suggesting an essential role for VP3 in forming birnaviruses specialized replication compartments. Here, combining high-resolution fluorescence and correlative light-electron microscopy with diverse molecular and biochemical analyses, we define how the IBDV protein VP3 targets and remodels host endosomes, and establish that endosome-associated replication is conserved in members of the Birnaviridae family. We show that IBDV VP3 targets early endosomes via the PtdIns(3)P effector Early Endosomal Antigen 1 (EEA1) to arrest their maturation and prompt their association with the Golgi complex via ESCPE-1-mediated retrograde transport. We further show that IPNV also exploits endosomal membranes for replication in a PtdIns(3)P dependent manner, although for this virus VP3 engages endosomes through an EEA1-independent mechanism yet to be determined. This work uncovers how birnaviruses exploit a single viral protein to orchestrate endosome remodeling and intracellular trafficking to establish specialized replication compartments while revealing both conserved and host-adapted features of birnaviruses replication.

cell biology↗

bioRxiv2025

Extracellular glutamine is essential in cell division and flagellar function in bloodstream forms of Trypanosoma brucei

Trypanosoma brucei is the etiologic agent of African trypanosomiasis, also known as sleeping sickness. In the mammalian host, T. brucei is present as replicative and non-replicative bloodstream forms (BSF) referred to as long slender and stumpy, respectively. In the insect vector, the developmental forms are procyclic (PCF), epimastigote, and metacyclic trypomastigote. It is well established that BSF use glucose as the main energy source, and PCF can use glucose but, in its absence, uses amino acids, mainly proline. Due to these facts, the metabolism of amino acids has been well studied in PCF, but less attention has been given to it in BSF. In the present work, we unveil the participation of glutamine (Gln), the most abundant amino acid in the human blood, in BSF proliferation. According to the data presented herein, in the absence of extracellular Gln, cell cycle progress, as well as kinetoplast and flagella distribution and function among daughter cells, are widely compromised, yielding polyploid multiflagellated cells with reduced motility. In addition, the Gln-poor medium resulted in cells with a massive alteration in the proteome glutamylation. These alterations were reverted when Gln was added to the culture media. An analysis of the glutamylproteome of cells incubated in Gln-poor medium, followed by a Gene Ontology (GO) analysis, suggested a relationship between glutamylation and biological processes such as gene expression and regulation, cell cycle, and bioenergetics metabolism, in addition to cytoskeleton dynamics in BSF of T. brucei.

cell biology↗

bioRxiv2025

Serotypes of Dengue Virus and Kdr Mutations F1534C, S989P, V410L, V1016I, and V1016G in Aedes aegypti and Aedes albopictus Mosquitoes from the commune of AbomeyCalavi, Southern Benin

Dengue is a viral infection transmitted by mosquitoes of the Aedes genus, responsible for millions of cases each year. In Benin, several outbreaks have been reported, particularly in Abomey-Calavi, where the first dengue-related death was recorded in 2019. In the absence of a specific treatment, vector control remains the primary preventive measure. However, the emergence of insecticide resistance, notably through kdr mutations, could compromise its effectiveness. This study aims to identify the dengue virus serotypes circulating in the commune of Abomey-Calavi and to assess the frequency of kdr mutations V410L, V1016G, V1016I, F1534C, and S989P in Aedes aegypti and Aedes albopictus mosquitoes. Mosquitoes were collected in August 2024 from four arrondissement Togba, Calavi, Akassato, and Godomey through morning and afternoon spraying. After morphological identification, molecular analyses were conducted to detect the viral serotypes and kdr mutations. A total of 218 Aedes mosquitoes were collected, with a predominance of Aedes aegypti (68.8%) compared to Aedes albopictus (31.2%). The overall dengue positivity rate was 23.39% (95% CI: 17.9 - 29.6). The most frequent serotype was DENV-3 (12.4%), followed by DENV-2 (6.9%), DENV-1 (5%), and DENV-4 (0.09%). Six mosquitoes were co-infected with two serotypes, including three with DENV-1 and DENV-4. kdr mutations were detected in both species, with frequencies of 45% for V1016G, 44% for S989P, 40% for F1534C, 22% for V410L, and 19% for V1016I. Four mosquitoes carried three simultaneous mutations, while twenty-two carried two. Two mosquitoes co-infected with two serotypes also carried two different mutations. These results highlight the active circulation of the dengue virus and the presence of kdr mutations in Aedes mosquitoes in Abomey-Calavi. However, no significant association was observed between dengue infection and kdr mutations, and their distribution was independent of the viral serotype. These findings emphasize the need for regular monitoring of kdr mutations to adapt vector control strategies and limit the spread of dengue.

biochemistry↗

bioRxiv2024

Whole Genome 3D Blood Biopsy Profiling of Canine Cancers: Development and Validation of EpiSwitch Multi-Choice Array-Based Diagnostic Test.

Veterinary oncology has a critical need for an accurate, specific, and sensitive non-invasive (blood) biomarker assay to assess multiple canine oncological indications early to better inform therapeutic interventions. Extended from clinical applications in human oncology, here we report on a novel 3D genomics approach to identify systemic blood biomarkers for canine diffuse large B-cell lymphoma (DLBCL), T-zone lymphoma (TZL), hemangiosarcoma (HSA), histiocytic sarcoma, osteosarcoma, and canine malignant melanoma, in a single assay format that encompasses multiple classes and phenotypes of cancer. In the validation of the independent test cohort the 3D whole-genome profiling in peripheral blood demonstrated high sensitivity and specificity for lymphomas and sarcomas as a class, with accuracy >80%; and high sensitivity and specificity for individual indications, with accuracy >89%. This study demonstrates a 3D genomic approach can be used to develop a non-invasive, blood-based test for multiple choice diagnosis of canine oncological indications. The modular EpiSwitch(R) Specific Canine Blood (EpiSwitch SCB) test promises to help veterinary specialists to diagnose the disease, make more informed treatment decisions, better utilize alternative effective treatments, minimize or avoid unnecessarily toxicity, and efficiently manage costs and resources.

molecular biology↗

bioRxiv2019

ABC transporters confer multidrug resistance to Drosophila intestinal stem cells

Adult stem cells can survive a wide variety of insults from ionizing radiation to toxic chemicals1-3. To date, the multidrug resistant features of stem cells have been characterized only in vertebrates, where there is a critical need to understand how cancer stem cells thwart chemotherapy drugs4-6. These studies reveal that the ability of both normal and cancer stem cells to survive toxins hinges on their high levels of expression of ABC transporters, transmembrane pumps that efflux lipophilic compounds out of cells7,8. This has been observed across a wide spectrum of vertebrate stem cells including breast, blood, intestine, liver, and skin, suggesting that high efflux ability and multidrug resistance may be general features of stem cells that distinguish them from their differentiated daughter cells. Here we show that these previously described vertebrate stem cell features are conserved in Drosophila intestinal stem cells. Using a novel in vivo efflux assay and multiple drug challenges, we show that stem cells in the fly intestine depend on two ABC transporters--one constitutively expressed and the other induced--for efflux and multidrug resistance. These results suggest that stem cell multidrug resistance by ABC transporters is a general stem cell feature conserved over 500 million years of evolution.

cell biology↗