Biology subjects

Peeters, M.

Publications and source records attributed to Peeters, M..

14 recordsLinked to original sources

bioRxiv2026

Comparison of Four Assays That Measure Antibodies to Ebola Virus Glycoprotein

The accurate measurement of Ebola virus (EBOV)-specific antibody responses is crucial to assessing immunity induced by EBOV infection or vaccination. For this purpose, the Filovirus Animal Nonclinical Group (FANG) anti-EBOV glycoprotein (GP1,2) ELISA is considered the "gold-standard". However, it has limitations such as high repeat-rates and variability, and low throughput. Here, we describe two new alternative assays: a Single-Molecule Assay Planar EBOV GP1,2 ELISA and a multiplexed EBOV GP1,2, EBOV nucleoprotein, and EBOV Viral Protein 40 Luminex assay, and compare these with two versions of the FANG ELISA. Samples were selected from participants receiving vaccine or placebo in a randomized, placebo-controlled, double-blinded study of two EBOV vaccines (PREVAIL 1), and a longitudinal cohort study of Ebola virus disease (EVD) survivors and their close contacts (PREVAIL 3). All four assays were concordant in their measurements of anti-EBOV GP1,2-specific immunoglobulin G responses, allowing for the determination of conversion equations for antibody measurements across assays. In addition, all four showed a similar ability to distinguish vaccine recipients from placebo recipients and EVD survivors from their close contacts. Compared to the FANG assays, the Quanterix and Luminex assays had lower variability, lower repeat rates, and higher throughput, making them good alternatives for future studies.

immunology↗

bioRxiv2026

Menaquinone depletion resensitises bedaquiline-resistant tuberculosis

Tuberculosis remains a leading cause of global mortality, and rising bedaquiline resistance threatens the effectiveness of current drug-resistant treatment regimens. Bedaquiline resistance typically arises through mutations in Rv0678 that upregulate drug efflux and confer cross-resistance to multiple drug classes. Here, we identify and optimise a chemical series targeting MenG, a central enzyme in the menaquinone biosynthesis pathway, yielding potent bactericidal inhibitors with in vivo efficacy. Strikingly, MenG inhibition restored bedaquiline susceptibility in efflux-mediated resistant strains, an effect confirmed in vivo where combination therapy achieved a 99.8% reduction in bacterial burden compared with bedaquiline alone. Potentiation also extended to pretomanid and other key agents. Disruption of upstream menaquinone and shikimate pathway enzymes produced similar resensitisation, establishing these pathways as tractable targets for restoring drug susceptibility in Mycobacterium tuberculosis. These findings provide a novel strategy to overcome bedaquiline resistance and strengthen future regimens for efflux-mediated drug-resistant tuberculosis.

microbiology↗

bioRxiv2025

High genetic diversity of mpox virus (MPXV) in three different rodent species in the Democratic Republic of the Congo (DRC)

Altough zoonotic spillover events continue to drive human mpox outbreaks in the Democratic Republic of the Congo (DRC), the wildlife reservoir of mpox virus (MPXV) remains unkown. To address this gap, we screened samples from 2,701 wild mammals, mainly rodents (59.7%), bats (26.4%) and shrews (12.1%). Only six (0.2%) animals were Orthopoxvirus (OPV) PCR positive. Near full-length MPXV sequences were obtained from two squirrels (Funisciurus anerythrus and Paraxerus sp.) and one soft furred mouse (Praomys jacksoni). A novel Taterapox virus was identified in a shrew (Crocidura cf. denti). All newly identified MPXV strains belong to clade Ia, but they cluster into different groups or subgroups, despite being collected from geographically close locations, and all are closely related to human MPXV strainsfrom the same regions. Our study provides for the first time clear evidence that MPXV diversity is not restricted to a single rodent host species nor confined to a geographic area. Importantly, MPXV positive Paraxerus and Praomys specimens were sampled close to Kisangani, a city with more than one million inhabitants, highlighting that spillover events can als ooccur in or near major cities, with more favorable conditions for interhuman transmissions and potential emergence of new lineages.

microbiology↗

bioRxiv2025

From Genes to Glands: Unraveling the Pivotal Influence of NtAGL66, an AGAMOUS-like Transcription Factor, on Glandular Trichome Development in Nicotiana tabacum

Glandular trichomes are specialized epidermal structures that play an essential role in plant defense by synthesizing, storing, and secreting specialized metabolites. This study investigates the function of NtAGL66, an AGAMOUS-like gene in Nicotiana tabacum, uncovering its role in the development of secretory heads in long glandular trichomes. Expression profiling reveals that NtAGL66 is specifically expressed in the developing secretory glands. Functional analyses show that NtAGL66 overexpression promotes the differentiation of the secretory structure, while CRISPR-Cas9-mediated knockout significantly reduces the capacity of trichomes to form functional secretory glands, highlighting its essential role in trichome specialization. Transcriptomic (RNA-seq) and functional genomic (DAP-seq) analyses indicate that NtAGL66 regulates also secondary metabolic pathways and is likely involved in broader transcriptional networks, including floral development. Notably, this includes genes such as NtTOE1, previously shown to control both floral organogenesis and glandular trichome formation in tomato. Moreover, NtAGL66 directly regulates the transcription factor NtGL2 through promoter binding. By identifying an AGAMOUS-like gene as a key regulator of secretory gland development, this study offers novel insights into the genetic mechanisms underlying glandular trichome differentiation and specialized metabolite biosynthesis in Solanaceae.

plant biology↗

bioRxiv2025

Insight into the genetic network governing long-stalked glandular trichome development in Nicotiana tabacum

Glandular trichomes play a pivotal role in plant defense against various biotic and abiotic stresses. To unravel the genetic network driving glandular trichome development in Nicotiana tabacum, we employed a transcriptional switch-based approach using heterologous expression of AmMIXTA, a MYB transcription factor from Antirrhinum majus. Through comprehensive RNA-seq analysis of transgenic tobacco seedlings where long-stalked glandular trichome development was induced in aerial parts, we identified a suite of differentially expressed genes, including several transcription factors, shedding light on the early transcriptional cascade governing this developmental process. Moreover, through confocal live cell imaging of transcriptional reporter lines, interaction studies and DAP-seq assays, we confirmed the involvement of NtZFP8, a gene identified in our study, in long-stalked glandular trichome development. Our findings support a model in which NtZFP8 regulates a gene network essential for this developmental process. This study underscores the effectiveness of our approach in decoding the regulatory landscape of glandular trichome development in N. tabacum and provides a valuable framework for future functional investigations. Key MessageGlandular trichomes are essential for plant defense. Using a transcriptional switch-based approach in Nicotiana tabacum, we identified key regulators, including NtZFP8, which controls long-stalked trichome development. Our study establishes a foundation for future functional analyses of candidate genes uncovered through this approach.

plant biology↗

bioRxiv2024

Assessing Ebola Virus Circulation in the Tshuapa Province (Democratic Republic of the Congo): A One Health Investigation of Wildlife and Human Interactions

The wildlife reservoir and spillover mechanisms of the Ebola virus remain elusive despite extensive research efforts in endemic areas. This study employed a One Health approach to examine the virus circulation in wildlife and the associated human exposure risks in the Tshuapa province of the Democratic Republic of the Congo. In 2021, we collected 1015 samples from 888 animals, predominantly small mammals, and 380 inhabitants of Inkanamongo village, the site of an Ebola virus disease outbreak in 2014. These samples were screened for evidence of current (RNA) or past (IgG antibodies) Ebola virus infections. We also conducted interviews with 167 individuals in the surrounding districts to assess their interactions with wildlife. While no Ebola virus RNA was detected in the wildlife samples, anti-orthoebolavirus IgG antibodies were found in 13 bats and 38 rodents. Among the human participants, 120 individuals had IgG antibodies against at least one orthoebolavirus antigen, with 12 showing seropositivity for two antigens of the same orthoebolavirus, despite not having a prior Ebola disease diagnosis. Furthermore, over 50% of respondents reported frequent visits to the forest to hunt a variety of wild animals, particularly ungulates and rodents, which could account for occasional viral spillovers. The absence of active Ebola virus circulation in wildlife may reflect seasonal patterns in reservoir ecology, like those observed in bats. Similarly, seasonal human activities, like hunting and foraging, may result in periodic exposure risks. These findings highlight the importance of continuous, multidisciplinary surveillance to monitor changes in seasonal spillover risks.

molecular biology↗

bioRxiv2024

Antibodies against medically relevant arthropod-borne viruses in the ubiquitous African rodent Mastomy natalensis

Over the past decades, the number of arthropod-borne virus (arbovirus) outbreaks has increased worldwide. Knowledge regarding the sylvatic cycle (i.e., non-human hosts/environment) of arboviruses is limited, particularly in Africa, and the main hosts for virus maintenance are unknown. Previous studies have shown the presence of antibodies against certain arboviruses (i.e., chikungunya-, dengue- and zika virus) in African non-human primates and bats. We hypothesize that small mammals, specifically rodents, may function as amplifying hosts in anthropogenic environments. The detection of RNA of most arboviruses is complicated by the viruss short viremic period within their hosts. An alternative to determine arbovirus hosts is by detecting antibodies, which can persist several months. We developed a high-throughput multiplex immunoassay to detect antibodies against 15 medically relevant arboviruses. We used this assay to assess almost 1,300 blood samples of the multimammate mouse, Mastomys natalensis from Tanzania. In 24% of the samples, we detected antibodies against at least one of the tested arboviruses, with high seroprevalences of antibodies reacting against dengue virus serotype one (7.6%) and two (8.4%) and chikungunya virus (6%). Seroprevalence was higher in females and increased with age, which could be explained by inherent immunity and behavioral differences between sexes and the increased chance of exposure to an arbovirus with age. We evaluated whether antibodies against multiple arboviruses co-occur more often than randomly and found that this may be true for some members of the Flaviviridae and Togaviridae. In conclusion, the development of an assay against a wide diversity of medically relevant arboviruses enabled the analysis of a large sample collection of one of the most abundant African small mammals. Our findings suggest a role in the transmission of multiple arboviruses by this ubiquitous rodent and provide a solid foundation for future molecular screening to elucidate the role in the arbovirus transmission cycle. Author summaryOne of the main causes of zoonotic related human morbidity and mortality is the transmission of arthropod-borne viruses such as dengue virus, Yellow Fever virus, and chikungunya virus. These viruses cannot only infect humans but also livestock, pets, and wildlife, though our understanding of their non-human hosts remains limited. Rodents are thought to be an interesting host for these viruses because they can be abundant, often live near humans and some are already known to be viral hosts. However, research has focused on non-human primates, neglecting other potential hosts. To address this gap, we have developed a high-throughput antibody test to screen rodent blood against 15 different arboviruses. Our findings reveal that a proportion of Mastomys natalensis, a common African rodent species, carry antibodies that (cross-)react against these viruses. We hypothesize that immunologically naive juveniles may drive transmission, particularly during population outbreaks. These outbreaks coincide with environmental conditions that are favorable for mosquitoes, the vectors of these viruses. Thus, increasing the risk of spillover to humans, livestock, and wildlife. Understanding the role of rodents in arbovirus transmission dynamics is crucial for mitigating zoonotic disease risks.

immunology↗

bioRxiv2023

Effects of biological and environmental factors on filovirus serology in bats in Guinea

BackgroundOutbreaks of Ebola disease emerge regularly in human populations on the African continent. This highly virulent haemorrhagic fever can be caused by different orthoebolaviruses from the Filoviridae family. Several bat species are believed to carry and transmit some of these viruses to people or other animal species. However, clear evidence is still lacking. Natural circulation and zoonotic transmissions of viruses are generally complex as they often involve several host species and are influenced by biological, environmental and anthropogenic factors. A better understanding of the role of bats and other wildlife in the emergence of Ebola disease outbreaks is crucial for their prevention and early detection. MethodsIn this longitudinal study we searched for antibodies against orthoebolaviruses in fruit bats in order to explore some of the factors which might influence their natural circulation. We performed serological tests on populations of 4 bat species (Eidolon helvum, Hypsignathus monstrosus, Myonycteris angolensis and Rousettus aegyptiacus) sampled longitudinally for 18 months (2018-2020) in Guinea. The analysis of 1,427 bat samples for antibodies directed against different orthoebolavirus species allowed us to test the influence of biological and environmental variables on seropositivity by using GLMM. ResultsResults showed that the presence of antibodies against one of the orthoebolaviruses antigen is more frequent in the Eidolon helvum and Rousettus aegyptiacus species, in males, in sexually immature adults, and during the dry season. ConclusionOur results suggest that host species, sex, age, reproductive life-cycle and season may play an important role in the circulation of filoviruses. This information can be used to guide further sampling to specifically characterize the orthoebolavirus species underlying the production of these antibodies and to adjust surveillance protocols at the interface between bats, humans and other animals.

microbiology↗

bioRxiv2023

A Bayesian analysis of birth pulse effects on the probability of detecting Ebola virus in fruit bats

Since 1976 various species of Ebolavirus have caused a series of zoonotic outbreaks and public health crises in Africa. Bats have long been hypothesised to function as important hosts for ebolavirus maintenance, however the transmission ecology for these viruses remains poorly understood. Several studies have demon-strated rapid seroconversion for ebolavirus antibodies in young bats, yet paradoxically few PCR studies have confirmed the identity of the circulating viral species causing these seroconversions. The current study presents an age-structured epidemiological model that characterises the effects of seasonal birth pulses on ebolavirus transmission within a colony of African straw-coloured fruit bats (Eidolon helvum). Bayesian calibration is performed using previously published serological data collected from Cameroon, and age-structure data from Ghana. The model predicts that annual birth pulses most likely give rise to annual outbreaks, although more complex dynamic patterns - including skip years, multi-annual cycles and chaos - may be possible. Weeks 30 to 31 of each year were estimated to be the most likely period for isolating the circulating virus in Cameroon. The probability that a previous PCR campaign failed to detect Ebola virus, assuming that it was circulating, was estimated to be one in two thousand. This raises questions such as (1) what can we actually learn from ebolavirus serology tests performed without positive controls? (2) are current PCR tests sufficiently sensitive? (3) are swab samples really appropriate for ebolavirus detection? The current results provide important insights for the design of future field studies aiming to detect Ebola viruses from sylvatic hosts, and can contribute to risk assessments concerning the timing of zoonotic outbreaks.

ecology↗

bioRxiv2023

Double Imprinted Nanoparticles for Sequential Membrane-to-Nuclear Drug Delivery

Nanoparticles functionalized with specific receptors (e.g., antibodies, peptides) are used for targeted drug delivery of anti-cancer agents but their side effects include hypersensitivity reactions, toxicity, inflammation, and life-threatening allergic reactions (Anaphylaxis) [1,2]. Consequently, double imprinted molecularly imprinted nanoparticles (nanoMIPs) against a linear epitope of breast cancer cell receptor estrogen alpha (ER) and loaded with an anti-cancer agent (doxorubicin, DOX) are synthesized via a solid-phase approach. Surface plasmon resonance (SPR) measurements reveal that the produced nanoMIPs exhibit KD values of 19 nM (against the epitope used for imprinting) and 10 nM (ER receptor), and thus rival the affinity of nanoparticles decorated with natural affinity reagents (e.g., antibodies, peptides), whilst offering the advantages of low-cost and enhanced cellular uptake due to the receptor mediated endocytosis. We present the results of in vitro flow cytometry that DOX loaded nanoMIPs can preferentially bind to MCF-7 (ER positive) breast cancer (BC) cells vs MDA-MB-231 (ER negative) BC cells. Confocal imaging witnessed the above results and showed the sequential movement of the DOX loaded nanoMIPs from membrane to the nucleus of MCF-7 BC cells and achieve delivery of DOX once internalised in the cells (directly to the nucleus). As a result, enhanced cell toxicity in MCF-7 cells ([~]80%) as compared to MDA-MB-231 cells ([~]15%) is observed via MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) cytotoxicity assay in a time dependent manner. Overall, this study provides a promising approach for the targeted drug delivery of chemotherapeutic drugs to breast cancer cells, which has the potential to significantly improve patient outcome whilst also reducing debilitating side effects of current treatment.

cancer biology↗

bioRxiv2023

Uncovering the hidden threat: single-organoid analysis reveals clinically relevant treatment-resistant and invasive subclones in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal diseases, characterized by a treatment-resistant and invasive nature. In-line with these inherent aggressive characteristics, only a subset of patients show a clinical response to the standard of care therapies, thereby highlighting the need for a more personalized treatment approach. In this study, we comprehensively unraveled the intra-patient response heterogeneity and intrinsic aggressive nature of PDAC on bulk and single-organoid resolution. We leveraged a fully characterized PDAC organoid panel (N=8) and matched our artificial intelligence-driven, live-cell organoid image analysis with retrospective clinical patient response. In-line with the clinical outcomes, we identified patient-specific sensitivities to the standard of care therapies (gemcitabine-paclitaxel and FOLFIRINOX) using a growth rate-based and normalized drug response metric. Moreover, the single-organoid analysis was able to detect resistant as well as invasive PDAC organoid clones, which was orchestrates on a patient, therapy, drug, concentration and time-specific level. Furthermore, our in vitro organoid analysis indicated a strong correlation with the matched patient progression-free survival (PFS) compared to the current, conventional drug response readouts. This work not only provides valuable insights on the response complexity in PDAC, but it also highlights the potential applications (extendable to other tumor types) and clinical translatability of our approach in drug discovery and the emerging era of personalized medicine.

cancer biology↗

bioRxiv2021

Using machine learning and big data to explore the drug resistance landscape in HIV

The authors have withdrawn this manuscript due to a duplicate posting of manuscript number 435621. Therefore, the author does not wish this work to be cited as reference for the project. Please cite and refer to the preprint 435621 (DOI: https://doi.org/10.1101/2021.03.16.435621). If you have any questions, please contact the corresponding authors.

bioinformatics↗

bioRxiv2018

A databank for intracellular electrophysiological mapping of the adult somatosensory cortex

BackgroundNeurons in the supragranular layers of the somatosensory cortex integrate sensory (bottom-up) and cognitive/perceptual (top-down) information as they orchestrate communication across cortical columns. It has been inferred, based on intracellular recordings from juvenile animals, that supragranular neurons are electrically mature by the fourth postnatal week. However, the dynamics of the neuronal integration in the adulthood is largely unknown. Electrophysiological characterization of the active properties of these neurons throughout adulthood will help to address the biophysical and computational principles of the neuronal integration.\n\nFindingsHere we provide a database of whole-cell intracellular recordings from 315 neurons located in the supragranular layers (L2/3) of the primary somatosensory cortex in adult mice (9-45 weeks old) from both sexes (females, N=195; males, N=120). Data include 361 somatic current-clamp (CC) and 476 voltage-clamp (VC) experiments, recorded using a step-and-hold protocol (CC, N=257; VC, N=46), frozen noise injections (CC, N=104) and triangular voltage sweeps (VC, 10 (N=132), 50 (N=146) and 100 ms (N=152)), from regular spiking (N=169) and fast-spiking neurons (N=66).\n\nConclusionsThe data can be used to systematically study the properties of somatic integration, and the principles of action potential generation across sexes and across electrically characterized neuronal classes in adulthood. Understanding the principles of the somatic transformation of postsynaptic potentials into action potentials will shed light onto the computational principles of intracellular information transfer in single neurons and information processing in neuronal networks, helping to recreate neuronal functions in artificial systems.

neuroscience↗

bioRxiv2018

Pisces: An Accurate and Versatile Variant Caller for Somatic and Germline Next-Generation Sequencing Data

MotivationNext-Generation Sequencing (NGS) technology is transitioning quickly from research labs to clinical settings. The diagnosis and treatment selection for many acquired and autosomal conditions necessitate a method for accurately detecting somatic and germline variants, suitable for the clinic.\n\nResultsWe have developed Pisces, a rapid, versatile and accurate small variant calling suite designed for somatic and germline amplicon sequencing applications. Pisces accuracy is achieved by four distinct modules, the Pisces Read Stitcher, Pisces Variant Caller, the Pisces Variant Quality Recalibrator, and the Pisces Variant Phaser. Each module incorporates a number of novel algorithmic strategies aimed at reducing noise or increasing the likelihood of detecting a true variant.\n\nAvailabilityPisces is distributed under an open source license and can be downloaded from https://github.com/Illumina/Pisces. Pisces is available on the BaseSpace SequenceHub as part of the TruSeq Amplicon workflow and the Illumina Ampliseq Workflow. Pisces is distributed on Illumina sequencing platforms such as the MiSeq, and is included in the Praxis Extended RAS Panel test which was recently approved by the FDA for the detection of multiple RAS gene mutations.\n\nContactpisces@illumina.com\n\nSupplementary informationSupplementary data are available online.

bioinformatics↗