Biology subjects

Brouwer, M.

Publications and source records attributed to Brouwer, M..

6 recordsLinked to original sources

bioRxiv2026

Anaerobic conditions increase plasmid transfer rates across Escherichia coli strains

Bacterial conjugation is the primary mechanism by which antibiotic resistance genes spread in microbial populations, yet our understanding of this process has been largely based on experiments conducted under aerobic conditions. This creates a fundamental disconnect: environments that are considered hotspots for gene exchange (e.g., the gut, abscesses, chronic wounds, and wastewater systems) are predominantly anaerobic. In this study, we investigate whether oxygen availability influences the transfer rate of a set of common ESBL-IncI1- and qnrS1-IncF plasmids in commensal Escherichia coli strains from chickens. We found that oxygen availability significantly shapes conjugation dynamics in a recipient strain-specific manner, with anaerobic conditions promoting higher ESBL-IncI1- plasmid transfer rates to commensal E. coli recipients. Conjugation rates of the ESBL-IncI1- plasmids to a laboratory strain of E. coli were several orders of magnitude higher and independent of oxygen level, while two qnrS1-IncF plasmids showed higher anaerobic rates. Our study reveals critical "oxygen blind spots" in conventional conjugation assays and suggests that conventional aerobic conjugation assays underestimate plasmid transfer rates in natural environments such as the chicken caeca. These findings highlight the importance of aligning experimental conditions with the physiological and ecological environments in which gene exchange naturally occurs. Tailoring these variables is essential for generating results that accurately reflect, predict, and potentially intervene in the horizontal spread of antimicrobial resistance.

microbiology↗

bioRxiv2025

A2AR-mediated inhibition of B cell maturation: a novel mechanism of immune suppression in cancer

High levels of extracellular adenosine, highly abundant in the tumor microenvironment, promote immune suppression mainly through the A2AR expressed by tumor-infiltrating immune cells. Here we show that plasma cells are the most negatively affected by adenosine among the immune cells present in the tumor microenvironment. Furthermore, both tonsillar and tumor-associated B cells, including germinal center (GC)-like B cells, plasma cells and plasma blasts (PCs and PBs, respectively, and collectively referred to as antibody-secreting cells (ASCs), express high levels of A2AR. Given the importance of tumor-infiltrating B and PCs in antitumor responses, we investigated how adenosine impairs their numbers and function. Triggering of A2AR inhibited B cell maturation into ASCs and immunoglobulin production in vitro, and impaired upregulation of PC genes upon stimulation. These effects were restored by inupadenant (EOS100850), a potent and highly selective small molecule A2AR antagonist. Spatial transcriptomics analysis of tumor biopsies from patients treated with inupadenant revealed that ASCs specifically increased in tertiary lymphoid structures. Altogether, these data demonstrate that A2AR plays a key role in adenosine-mediated inhibition of B cell maturation toward ASCs through a B cell-intrinsic mechanism, and that this effect is fully reverted by inupadenant.

immunology↗

bioRxiv2024

Task-irrelevant stimuli reliably boost phasic pupil-linked arousal but do not affect decision formation

The arousal systems of the brainstem, specifically the locus coeruleus-noradrenaline system, respond "phasically" during decisions. These central arousal transients are accompanied by dilations of the pupil. Mechanistic attempts to understand the impact of phasic arousal on cognition would benefit from the ability to experimentally manipulate arousal in a temporally precise manner. Here, we evaluated a non-invasive candidate approach for such a manipulation in humans: presenting task-irrelevant auditory stimuli at different latencies during the execution of a challenging task. Task-irrelevant auditory stimuli drive responses of brainstem nuclei involved in the control of pupil size. But it is unknown whether such sound-evoked responses mimic the central arousal transients evoked during cognitive computations. A large body of evidence has implicated central arousal transients in a bias reduction during challenging perceptual decisions. We thus used challenging visual decisions as a testbed, combining them with task-irrelevant sounds of varying onset latency or duration. Across three experiments, the sounds consistently elicited well-controlled pupil responses that superimposed onto task-evoked responses. While we replicated a negative correlation between task-evoked pupil responses and bias established in previous work, the task-irrelevant sounds had no behavioral effect. This dissociation suggests that cognitive task engagement and task-irrelevant sounds may recruit distinct neural systems contributing to the control of pupil size.

neuroscience↗

bioRxiv2023

Desynapsis in potato is caused by StMSH4 mutant alleles and leads to either highly uniform unreduced pollen or sterility

The balanced segregation of homologous chromosomes during meiosis is essential for fertility and is mediated by crossovers. A strong reduction of crossovers leads to desynapsis, a process in which pairing of homologous chromosomes is abolished before metaphase I. This results in a random segregation of univalent and the production of unbalanced and sterile gametes. However, if desynapsis is combined with another meiotic alteration that restitutes the first meiotic division, then uniform and balanced unreduced gametes, essentially composed of non-recombinant homologs, are produced. This mitosis-like division is of interest to breeders because it transmits most of the parental heterozygosity to the gametes. In potato, desynapsis is a recessive trait that was tentatively mapped to chromosome 8. In this article, we have fine-mapped the position of the desynapsis locus and identified StMSH4, an essential component of the class I crossover pathway, as the most likely candidate gene. A seven base-pair insertion in the second exon of StMSH4 was found to be associated with desynapsis in our mapping population. We also identified a second allele with a 3820 base-pair insertion and confirmed that both alleles cannot complement each other. Such non-functional alleles appeared to be common in potato cultivars. More than half of the varieties we tested are carriers of mutational load at the StMSH4 locus. With this new information, breeders can choose to remove desynaptic alleles from their germplasm to improve fertility or to use them to produce highly uniform unreduced gametes in alternative breeding schemes.

plant biology↗

bioRxiv2020

Jumping back and forth: anthropozoonotic and zoonotic transmission of SARS-CoV-2 on mink farms

The zoonotic origin of the SARS-CoV-2 pandemic is still unknown. Animal experiments have shown that non-human primates, cats, ferrets, hamsters, rabbits and bats can be infected by SARS-CoV-2. In addition, SARS-CoV-2 RNA has been detected in felids, mink and dogs in the field. Here, we describe an in-depth investigation of outbreaks on 16 mink farms and humans living or working on these farms, using whole genome sequencing. We conclude that the virus was initially introduced from humans and has evolved, most likely reflecting widespread circulation among mink in the beginning of the infection period several weeks prior to detection. At the moment, despite enhanced biosecurity, early warning surveillance and immediate culling of infected farms, there is ongoing transmission between mink farms with three big transmission clusters with unknown modes of transmission. We also describe the first animal to human transmissions of SARS-CoV-2 in mink farms. One sentence summarySARS-CoV-2 transmission on mink farms.

genomics↗

bioRxiv2020

Unravelling the effect of a potentiating anti-Factor H antibody on atypical hemolytic uremic syndrome associated factor H variants

The complement system plays an important role in our innate immune system. Complement activation results in clearance of pathogens, immune complex and apoptotic cells. The host is protected from complement-mediated damage by several complement regulators. Factor H (FH) is the most important fluid-phase regulator of the alternative pathway of the complement system. Heterozygous mutations in FH are associated with complement-related diseases such as atypical hemolytic uremic syndrome (aHUS) and age-related macular degeneration. We recently described an agonistic anti-FH monoclonal antibody that can potentiate the regulatory function of FH. This antibody could serve as a potential new drug for aHUS patients and alternative to C5 blockade by Eculizumab. However, it is unclear whether this antibody can potentiate FH mutant variants in addition to wild type FH. Here, the functionality and potential of the agonistic antibody in the context of pathogenic aHUS-related FH mutant proteins was investigated. The binding affinity of recombinant WT FH, and the FH variants, W1183L, V1197A, R1210C, and G1194D to C3b was increased upon addition of the potentiating antibody and similarly, the decay accelerating activity of all mutants is increased. The potentiating anti-FH antibody is able to restore the surface regulatory function of most of the tested FH mutants to WT FH levels. In conclusion, our potentiating anti-FH is broadly active and able to enhance both WT FH function as well as most aHUS-associated FH variants tested in this study.

immunology↗