Biology subjects

van Wijk, R.

Publications and source records attributed to van Wijk, R..

4 recordsLinked to original sources

bioRxiv2026

Activity of a three-phage combination against Mycobacterium tuberculosis in disease-relevant conditions

Phage therapy offers promise to combat antimicrobial resistance, including drug-resistant tuberculosis (TB). Understanding phage activity against Mycobacterium tuberculosis (Mtb) adapted to physiologic microenvironments, such as hypoxia and acidity in granulomas, is essential since these conditions induce non-replicating states. We evaluated a phage combination against Mtb under hypoxic, acidic (pH 5.5), and stationary-phase conditions in vitro. In planktonic Mtb growth conditions, phage concentrations increased around day seven followed by a significant reduction in Mtb H37Rv load, which was maintained over 31 days. Phage addition prevented regrowth was observed with rifampicin and isoniazid alone. Individual phage stability was differentially affected by acidic media conditions, resulting in variability of antimycobacterial activity. In hypoxic conditions and stationary growth experiments, phage titers remained stable over time with no change in mycobacterial load compared to controls. Model-based predictions were able to adequately capture phage-mycobacterial interactions with and without rifampicin. The lack of antimycobacterial activity in assays with non-replicating mycobacteria suggest that phages need actively replicating mycobacteria to exert lytic activity. Stable phage concentrations in assays with non-replicating mycobacteria suggests low grade phage replication in these conditions. Established models can support future study design through simulations of different experimental scenarios.

microbiology↗

bioRxiv2023

Ectopic Expression of Distinct PLC Genes Identifies 'Compactness' as Novel Architectural Shoot Strategy to Cope with Drought Stress

Phospholipase C (PLC) has been implicated in several stress responses, including drought. Overexpression (OE) of PLC has been shown to improve drought tolerance in various plant species. Arabidopsis contains nine PLC genes, subdivided into four clades. Earlier, OE of PLC3, -5 or -7 were found to increase Arabidopsis drought tolerance. Here, we confirm this for three other PLCs: PLC2, the only constitutively expressed AtPLC; PLC4, reported to have reduced salt tolerance; and PLC9, of which the encoded enzyme was presumed to be catalytically inactive. To compare each PLC and to discover any other potential phenotype, two independent OE lines of six AtPLC genes, representing all four clades, were simultaneously monitored with the GROWSCREEN FLUORO phenotyping platform, under both control- and mild drought conditions. To investigate which tissues were most relevant to achieve drought survival, we additionally expressed AtPLC5 using 13 different cell- or tissue-specific promoters. While no significant differences in plant size, biomass or photosynthesis were found between PLC lines and wild-type (WT) plants, all PLC-OE lines, as well as those tissue-specific lines that promoted drought survival, exhibited a stronger decrease in convex hull perimeter (= increase in compactness) under water deprivation compared to WT. Increased compactness has not been associated with drought or decreased water loss before, though a hyponastic decrease in compactness in response to increased temperatures has been associated with water loss. We pose that increased compactness leads to decreased water loss and potentially provides a new breeding trait to select for drought tolerance.

plant biology↗

bioRxiv2019

The BIR2/BIR3-interacting Phospholipase D gamma 1 negatively regulates immunity in Arabidopsis

Plants have evolved effective strategies to defend themselves against pathogen invasion. Starting from the plasma membrane with the recognition of microbe-associated molecular patterns (MAMPs) via pattern recognition receptors, internal cellular signaling pathways are induced to ultimately fend off the attack. Phospholipase D (PLD) hydrolyzes membrane phospholipids to produce phosphatidic acid (PA), which has been proposed to play a second messenger role in immunity. The Arabidopsis PLD family consists of 12 members and for some a specific function in resistance towards a subset of pathogens has been shown. We demonstrate here that Arabidopsis PLD{gamma}1, but not its close homologs PLD{gamma}2 and PLD{gamma}3, is specifically involved in plant immunity. Genetic inactivation of PLD{gamma}1 resulted in increased resistance towards the virulent bacterium Pseudomonas syringae pv. tomato DC3000 and the necrotrophic fungus Botrytis cinerea. As pld{gamma}1 mutant plants responded with elevated levels of reactive oxygen species to MAMP-treatment, a negative regulatory function for this PLD isoform is proposed. Importantly, PA levels in pld{gamma}1 mutants were not affected compared to stressed wild-type plants, suggesting that alterations in PA levels are unlikely the cause for the enhanced immunity in the pld{gamma}1 line. Instead, the plasma-membrane-attached PLD{gamma}1 protein colocalized and associated with the receptor-like kinases BIR2 and BIR3, which are known negative regulators of pattern-triggered immunity. Moreover, complex formation of PLD{gamma}1 and BIR2 was further promoted upon MAMP-treatment. Hence, we propose that PLD{gamma}1 acts as a negative regulator of plant immune responses in complex with immunity-related proteins BIR2 and BIR3.\n\nOne-sentence summaryA phospholipase D is a novel negative regulator of plant immunity and forms complexes with regulatory receptor-like kinases.

plant biology↗

bioRxiv2017

The fluid membrane determines mechanics of red blood cell extracellular vesicles and is softened in hereditary spherocytosis

Extracellular vesicles (EVs) are widely studied regarding their role in cell-to-cell communication and disease, as well as for applications as biomarker or drug delivery vehicle. EVs contain both membrane and intraluminal proteins, affecting their structural properties and thereby likely their functioning. Here, we use atomic force microscopy for the mechanical characterization of red blood cell (RBC) EVs from healthy individuals as well as from a patient with hereditary spherocytosis (HS) due to ankyrin deficiency. We show that the EVs are packed with proteins, yet their response to indentation is similar to that of a fluid lipid vesicle lacking proteins. The bending modulus of RBC EVs of healthy donors is ~15 kbT, agreeing well with the bending modulus of the RBC membrane. Surprisingly, whereas RBCs become more rigid in HS, the excreted vesicles of a patient with this blood disorder have a significantly (~50%) lower bending modulus than donor EVs. These results shed new light on the mechanism and effects of EV budding and may underlie the reported increase in vesiculation and stiffening of RBCs in hereditary spherocytosis patients.

biophysics↗