Biology subjects

de Jong, A.

Publications and source records attributed to de Jong, A..

16 recordsLinked to original sources

bioRxiv2026

Genomic status of the Eurasian curlew Numenius arquata : estimating Essential Biodiversity Variables and selection signals for a declining migratory bird

Understanding how contemporary population declines affect the genomic diversity and structure of threatened species is important for effective conservation. The Eurasian curlew (Numenius arquata) is experiencing severe population declines across Europe, with Ireland among the most extreme, showing declines exceeding 90% over 40 years. Genomic data are increasingly incorporated into policy and used to assess conservation status by estimating genetic diversity, differentiation, inbreeding, effective population size, and adaptive divergence. Such data for curlew is scarce, and the population structure among northern and north-western European breeding populations remains unclear. To address this, we generated whole-genome resequencing data for 56 curlews across Ireland, Britain and Sweden. Irish and British populations showed minimal interpopulation differentiation, but both were substantially differentiated from Sweden. This was apparent from principal component analysis, and admixture and FST analyses. Measures of genetic diversity (nucleotide diversity, heterozygosity, Watterson's{theta} ) were similar across populations. A slightly elevated Tajima's D in Ireland, along with elevated FROH in Ireland and Britain relative to Sweden, may be the early genomic signs of recent population declines. We identified locally selected candidate genes. These had putative roles in metabolic processes, the immune response, and were potentially associated with distinct migratory behaviours and environmental conditions. We find a potential lag in genomic effects of decline being detectable following population contraction. We also show highly migratory species can exhibit differentiation in ecologically relevant traits, potentially driven by high site fidelity. These findings warrant consideration in translocation planning and broader conservation strategies.

genomics↗

bioRxiv2026

CD1a-Mediated Presentation of Canonical Microbial Peptides to T Cells

Langerhans cells express the nonpolymorphic antigen-presenting molecule CD1a, positioning them as contributors to host immunity against Mycobacterium leprae in human leprosy. CD1a was originally shown to present non-canonical lipopeptide antigens such as dideoxymycobactin and chemically diverse hydrophobic ligands. Here, we generated CD4 T cell lines from leprosy lesions that recognized M. leprae in a CD1a-restricted manner. Unexpectedly, antigen recognition was protease-sensitive, prompting biochemical purification that identified two microbial protein antigens: LppX, a 25-kDa lipoglycoprotein, and Ag85A, a 30-kDa secreted protein with no known lipid modification. Recombinant proteins activated the corresponding T cell lines in a CD1a-dependent manner. Epitope mapping identified 12-mer peptides that fully reconstituted antigenicity, were conserved between M. leprae and M. tuberculosis, and elicited robust, dose-dependent IFN-{gamma} production and T cell proliferation, establishing that DNA-encoded, ribosomally translated peptides serve as CD1a-restricted cognate antigens. Biochemical analyses showed peptide binding to CD1a, supported by isoelectric focusing and surface plasmon resonance (KD [~]75 M for Ag85A). CD1a-peptide tetramers specifically stained cognate T cells, soluble CD1a was sufficient to present peptide antigen, and transfer of the LppX-specific TCR into naive T cells restored antigen responsiveness. Using CD1a-peptide tetramers, we identified antigen-specific T cells enriched in patients undergoing reversal reactions compared with patients with lepromatous leprosy and healthy donors. The CD1a-restricted T cell lines secreted IFN-{gamma} and IL-26, cytokines with established antimicrobial activity. Together, these findings demonstrate that CD1a can present canonical microbial peptides as part of a cell-mediated immune response in leprosy, extending the known spectrum of CD1a ligands. Because CD1a is nonpolymorphic and presents antigens to antimicrobial T cells, CD1a-peptide complexes may provide a broadly applicable platform for studying, detecting, and potentially targeting mycobacterial immunity.

immunology↗

bioRxiv2025

Pyocyanin produced by Pseudomonas aeruginosa Creates Legacy Effects That Boost Antibiotic Resistance Evolution in Enterococci

Polymicrobial infections are small communities of multiple interacting bacterial species. Interactions among constituent species may modify the growth of community members in the presence of antibiotics, for example via degradation of the antibiotic or induction of specific resistance mechanisms. However, for most polymicrobial infections the nature of such interactions is opaque, while they may affect both treatment efficacy and the evolution of antibiotic resistance. Here, we describe that past interaction of enterococci with Pseudomonas aeruginosa creates legacy effects that substantially alter their antibiotic tolerance and resistance evolution. Specifically, we find that the temporary exposure to pyocyanin, a secondary metabolite produced by P. aeruginosa, increases the efflux in enterococci. These tolerance legacy effects promote the evolution of antibiotic resistance of enterococci. This work shows that transient interactions in polymicrobial communities can alter the evolutionary fate of community members.

microbiology↗

bioRxiv2025

EXPRESSION OF CONJUGATION GENES IS CONTROLLED BY PROCESSIVE ANTITERMINATION AND A NOVEL ZIPPER-TYPE TRANSCRIPTIONAL ATTENUATION MECHANISM

Proper expression of genes clustered in operons, particularly large operons, can be complex, often consisting of multiple regulatory switches. The conjugation operon present on the Bacillus subtilis conjugative plasmid pLS20 is over 32 kb long. This operon starts with a 456 nt leader region, which is followed by the first two genes of the operon, encoding a two-component processive antitermination system. Here, we demonstrate that the long leader region encodes a transcriptional attenuator that we named cATTpLS20. In vivo and in vitro analyses showed that the attenuator is composed of three segments: a stem-loop structure with a long imperfect stem that is preceded by a sequence that may form a weak stem-loop and followed by a sequence that may form an intrinsic terminator. Sequences of the upstream stem loop and downstream terminator are complementary, allowing further extension of the long stem, thereby generating an antiterminator conformation. Based on similarity with a zipper we coined this the zipper-type attenuator. Similar zipper-type attenuators are present upstream of the first genes of conjugation operons of all pLS20 family plasmids, as well as on many other conjugative plasmids in Gram-positive bacteria, suggesting that a common attenuation mechanism regulates expression of many conjugative operons. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=126 SRC="FIGDIR/small/689506v1_ufig1.gif" ALT="Figure 1"> View larger version (18K): org.highwire.dtl.DTLVardef@a86a7eorg.highwire.dtl.DTLVardef@e787f8org.highwire.dtl.DTLVardef@8fdb75org.highwire.dtl.DTLVardef@90f842_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2025

Mapping unsolved lipidomes accelerates lipid discovery in major bacterial pathogens

Unlike gene-first approaches to understanding bacterial pathogenesis, molecule-forward discovery can uncover unexpected chemical diversity. Here, new lipidomic analytical methods and quality metrics defined the large scope of unknown lipids in the worlds deadliest pathogen, Mycobacterium tuberculosis (Mtb). This map allowed rapid discovery of Mtb lysyldiacylglycerol linked to the biosynthetic gene lysX, which controls in vivo infection outcomes in moth larvae, mice, guinea pigs, and here, zebrafish. A broader search for orthologous lysyltransferase domains identified the Staphylococcus aureus virulence gene mprF, where the same lipoamino acid was shown to be a previously unknown biosynthetic product. Thus, lipidomic mapping showed that the cell envelope composition of well-studied bacterial pathogens remains substantially unsolved and offers a new way to generate lists of discoverable lipids to accelerate molecular discovery.

microbiology↗

bioRxiv2025

Reversible Sandwich-Based Particle Nanoswitch for Continuous Protein Monitoring at Picomolar Concentrations with Automated Calibration

Continuous monitoring of specific proteins is essential for understanding the dynamics of biological systems and for enabling real-time measurement-and-control strategies in bioprocesses. Ideally, sensors for continuous monitoring should be intrinsically reversible and able to perform accurate measurements over long time spans. Here, we present a particle nanoswitch sensor containing two different antibody fragments that bind reversibly to a protein of interest and thus form transient sandwich complexes. The antibody fragments are incorporated into the sensor using site-specific conjugation strategies to achieve optimal antibody orientation. Short-lived sandwich complexes are detected with single-molecule resolution, by tracking the motion of tethered particles. The sensing concept is demonstrated for lactoferrin, an iron-binding and immune-modulating protein. We show continuous measurements of picomolar concentrations with a response time of [~]10 min over periods of 12-15 h. Automated calibration strategies are described that result in a mean absolute relative difference below 10% compared to reference measurements. These results demonstrate how continuous fast protein sensing at picomolar concentrations can be achieved using reversible sandwich-based particle nanoswitches, enabling long-term monitoring of dynamic bioprocesses.

bioengineering↗

bioRxiv2025

The infection cycle of the haloarchaeal virus HFTV1 is tightly regulated and strongly inhibits motility of its host

Although viruses have been shown to infect all domains of life, our understanding of the genetic program behind the exploitation of host resources to produce progeny virions is thus far limited to several bacterial viruses. Therefore, to elucidate the transcriptome of euryarchaeal viruses and their hosts, we employed RNAseq analysis of samples taken at different time points from Haloferax gibbonsii LR2-5 cultures infected with the lytic model virus Haloferax Tailed Virus 1 (HFTV1). While following the transcription of viral genes throughout the infective life cycle, we observed a tight temporal regulation of viral transcripts as well as differential expression from within viral gene clusters. Furthermore, anti-sense RNAs (asRNAs) appear to play an important role in support of the timing of late-expressed viral genes. Therefore, with many differentially expressed transcripts, including intragenic transcripts and asRNAs, the regulatory machinery employed by HFTV1 contrasts with viral model systems (based on phages), in which antitermination and/or alternative polymerases (seemingly lacking in HFTV1) are more widespread. When looking into differentially expressed host genes, we observed a strong downregulation of genes involved in motility, such as the archaellum and chemotaxis machinery, which was confirmed with swimming assays of HFTV1 infected cells. This might be a strategy of the virus to redirect energy flowing into movement towards the production of virions. In conclusion, this work thus provides a stepping stone for further exploration of the intriguing strategies of viral transcriptional regulation of their infection cycle across the domains of life. IMPORTANCEViruses infect members of all three domains of life, including Archaea. Euryarchaea are widespread microorganisms found in various environments such as the human gut and solar salterns. Due to the exceptional availability of cell biology and genetic tools of some salt-loving archaea, they are a model system to extrapolate from. Insights into the regulation of viral infections are of particular importance, especially since HFTV1, has been adopted as a model virus by the archaeal viral community. We found that, while harboring parallels with bacterial viruses, such as tight temporal regulation, HFTV1 harbors an impressive number of differentially expressed transcriptional units. Furthermore, anti-sense RNAs and intragenic regulatory elements seem to play a much more prominent role in HFTV1 gene expression. Thus, this work challenges current models and provides valuable new insights into the gene regulation of viral infection of archaea, which mark similarities and differences with viruses from other domains of life.

microbiology↗

bioRxiv2025

Serotonin modulation of metabolism and stress response in Pseudomonas fluorescens

BackgroundPseudomonas fluorescens is a gram-negative bacterium with a remarkable metabolic and physiological versatility that enables it to adapt and colonize diverse ecological niches, including the human small intestine. While serotonin is primarily found in high concentrations in gut tissue, its levels in the lumen can be elevated in conditions such as celiac disease, where P. fluorescens is also found in increased abundance. The potential effects of serotonin on P. fluorescens in such contexts remain unclear. ResultsWe demonstrate that P. fluorescens metabolizes serotonin primarily into 5-hydroxyindole-3-acetic acid (5-HIAA) and, to a lesser extent, into 5-hydroxytryptophol and N-acetylserotonin. Gene expression analysis revealed significant changes in oxidative stress-related pathways over time, and proteomic analysis confirmed the shifts seen particularly in amino acid catabolic pathways. Serotonin metabolism also enhanced bacterial resistance to oxidative stress, suggesting a protective role. ConclusionsThe findings reveal a novel mechanism by which serotonin modulates the metabolism and stress responses of P. fluorescens. This study provides insight into how P. fluorescens adapts to serotonin-rich environments, such as in celiac disease, and may inform future research on microbial interactions with host-derived metabolites in disease contexts.

microbiology↗

bioRxiv2024

Comprehensive Unbiased Analysis of Vascular Tissue Changes in Accelerated Atherosclerosis Using High-Resolution Ultrasound combined with Photoacoustic Imaging

Venous bypass grafts are commonly used to circumvent complex coronary or peripheral artery occlusions. The patency rates, however, are hampered due to accelerated buildup of atherosclerotic lesions in the vein graft wall. Identification of unstable plaques is crucial to guide clinical decision making. In this study, we employ advanced high-resolution ultrasound (US) coupled with spectral photoacoustic imaging (sPAI) to enhance the accurate visualization and analysis of tissue composition in vivo. By applying unbiased spectral analysis, we investigate the composition and plaque instability in a murine vein graft model. MethodMale hypercholesterolemic ApoE3*Leiden mice and normocholesterolemic C57BL/6 mice underwent vein graft surgery in which a caval vein from a donor mouse was interpositioned into the arterial circulation of a recipient at the sight of the right common carotid artery. US imaging with sPAI was conducted on 7, 14, 21, and 28 days after surgery. Spectral curves from the near-infrared (NIR) I region, spanning 680 to 970nm, were extracted using a data-driven approach. Component discovery and cross-correlation analysis were performed with Matlab, and ImageJ reconstructed the components within 3D images. At the endpoint histological analysis of the vein grafts was performed. ResultsAnalysis of the NIRI region revealed distinct components, with 7 and 10 components tested in the cross-correlation map. Relative abundance values identified melanin, oxidized hemoglobin, deoxygenized hemoglobin, lipids, and collagen. Lipids and collagen spectra accurately identified lipid and collagen-rich tissues in vivo. The sPAI analysis of of the vein graft wall in vivo resulted in a 8.7% lipids in the vein graft wall compared to 1.8% lipids in the histological analysis at t=28d. For vein grafts from ApoE*3-Leiden mice no differences in the lipid positive area was observed between the sPAI analysis or histological quantification. The percentages collagen present in the vein graft walls from both strains analyzed via sPAI and histological showed comparable results at t=28d. ConclusionOur study demonstrates that sPAI can be utilized for compositional analysis of murine tissue in an unbiased manner. This methodology can be used to enhance our understanding of vein graft dynamics and holds promise to advance non-invasive characterization of vascular diseases to ultimately guide clinical decision making.

bioinformatics↗

bioRxiv2024

PLA2G15 is a Lysosomal BMP Hydrolase with Ester Position Specificity and Its Targeting Ameliorates Lysosomal Disease

Lysosomes catabolize lipids and other biological molecules, a function essential for cellular and organismal homeostasis. Key to lipid catabolism in the lysosome is bis(monoacylglycero)phosphate (BMP), a major lipid constituent of intralysosomal vesicles and a stimulator of lipid-degrading enzymes. BMP levels are altered in a broad spectrum of human conditions, including neurodegenerative diseases. While a lysosomal BMP synthase was recently discovered, the enzymes that mediate BMP turnover has remained elusive. Here we show that the lysosomal phospholipase PLA2G15 is a physiological BMP hydrolase. We further demonstrate that BMPs resistance to hydrolysis in the lysosome is conferred by the combination of its unique sn2, sn2 esterification position and stereochemistry, as neither feature alone is sufficient to provide this resistance. Purified PLA2G15 catabolizes most BMP species derived from cell and tissue lysosomes under acidic conditions. Furthermore, PLA2G15 catalytic activity against synthesized BMP stereoisomers with primary esters was comparable to its canonical substrates challenging the long-held thought that BMPs unique stereochemistry is sufficient to confer resistance to acid phospholipases. Conversely, BMP with secondary esters and S,S stereoconfiguration is intrinsically stable in vitro and requires acyl migration for hydrolysis in lysosomes. Consistent with our biochemical data, PLA2G15-deficient cells and tissues accumulate multiple BMP species, a phenotype reversible by supplementing wildtype PLA2G15 but not its catalytically dead mutant. In addition, targeting PLA2G15 to increase BMP reverses the cholesterol phenotype in Niemann Pick Disease Type C (NPC1) patient fibroblasts and significantly ameliorates disease pathologies in NPC1-deficient mice leading to extended lifespan. Our findings establish the rules that govern the stability of BMP in the lysosome and identify PLA2G15 as a lysosomal BMP hydrolase and a potential target for therapeutic intervention in neurodegenerative diseases.

cell biology↗

bioRxiv2022

Candida khanbhai sp. nov., a new clinically relevant yeast within the Candida haemulonii species complex

Invasive fungal infections caused by non-albicans Candida species are increasingly reported. Recent advances in diagnostic and molecular tools enabled better identification and detection of these emerging pathogenic yeasts. Several of these emerging species belong to the Candida haemulonii species complex, which attracted much attention due to the rapid global emergence of its multi-drug resistant member Candida auris. Here, we describe a new clinically relevant yeast isolated from geographically distinct regions, representing the proposed novel species Candida khanbhai, member of the C. haemulonii species complex. Moreover, several members of the C. haemulonii species complex were observed to be invalidly described, including Candida auris and Candida vulturna. Hence, the opportunity was taken to correct this here, formally validating the names of various yeast species.

microbiology↗

bioRxiv2020

Enrichment of novel Verrucomicrobia, Bacteroidetes and Krumholzibacteria in an oxygen-limited, methane- and iron-fed bioreactor inoculated with Bothnian Sea sediments

Microbial methane oxidation is a major biofilter preventing larger emissions of this powerful greenhouse gas from marine coastal areas into the atmosphere. In these zones, various electron acceptors such as sulfate, metal oxides, nitrate or oxygen can be utilized. However, the key microbial players and mechanisms of methane oxidation are poorly understood. In this study, we inoculated a bioreactor with methane- and iron-rich sediments from the Bothnian Sea in order to investigate microbial methane and iron cycling under low oxygen concentrations. Using metagenomics, we observed shifts in the microbial community over approximately 2.5 years of bioreactor operation. Marker genes for methane and iron cycling, as well as respiratory and fermentative metabolism, were investigated. Metagenome-assembled genomes representing novel Verrucomicrobia, Bacteroidetes and Krumholzibacteria were recovered and revealed potential for methane oxidation, organic matter degradation, and iron cycling, respectively. This work brings new insights into the identity and metabolic versatility of microorganisms that may be members of such functional guilds in coastal marine sediments and highlights that the methane biofilter in these sediments may be more diverse than previously appreciated. ImportanceDespite the essential role of microorganisms in preventing most methane in the ocean floor to reach the atmosphere, comprehensive knowledge on the identity and the mechanisms employed by these microorganisms is still lacking. This is problematic because such information is needed to understand how the ecosystem functions in the present and how microorganisms may respond to climate change in the future. Here, we enriched and identified novel taxa potentially involved in methane and iron cycling in an oxygen-limited bioreactor inoculated with methane- and iron-rich coastal sediments. Metagenomic analyses provided hypotheses about the mechanisms they may employ, such as the use of oxygen at very low concentrations. The implication of our results is that in more shallow sediments, where oxygen-limited conditions are present, the methane biofilter is potentially composed of novel, metabolically versatile Verrucomicrobia that could contribute to mitigating methane emissions from coastal marine zones.

microbiology↗

bioRxiv2020

Alternative phage-host interaction in Lactococcus lactis: the carrier state drives rapid evolution of phages

Lactococcus lactis is a lactic acid bacterium widely used as starter culture for the manufacture of fermented milk products like quark, buttermilk and cheese. Bacteriophage infection of starter cultures is one of the biggest causes of fermentation failure and, therefore, lactococcal phages have received great attention from the scientific community in the past decades. In this work we present evidence for the establishment of a carrier state life cycle (CSLC) by a bacteriophage belonging to the c2 species, in the model laboratory strain L. lactis MG1363. Our results show that infection of L. lactis MG1363 with a second, dissimilar, c2 bacteriophage can induce the CSLC phage to enter an active lytic life cycle. The viral progeny obtained after this infection is a mixed population of phages with differences in their genome sequences and host ranges, indicative of an extremely rapid evolution process. We discuss the possible implications of this phage-host interaction, both with respect to bacteriophage evolution and phage adaptation to different hosts. IMPORTANCEOur results broaden the current know-how on the yet poorly investigated phage-host interaction mechanism of CSLC, propose a new bacteriophage evolution mechanism, and demonstrate that the outcome of phage infections is possibly more intricate than presently acknowledged.

evolutionary biology↗

bioRxiv2019

Are Railways detrimental to bird populations? A BDACI study on the Construction of the Bothnia Line Railway

Railways, like roads, are commonly considered bad for birdlife, but supporting data are very scarce. We conducted a 14-year before-during-after control-impact (BDACI) study of birds in agricultural landscapes affected by the construction of the Bothnia Line Railway (BLR) in northern Sweden. The \"during\" phase was split into two phases, one for the true construction period and one for the years when the railway was ready but not trafficked. Avian biodiversity increased in impact sites (N=13), but not in control sites (N=6). The numbers of breeding territories decreased correspondingly in impact and control sites, but trends differed between species and sites. Developments in the Degernas site demonstrated that mitigation could be successful. Finally, there was no support for a shying-away effect of the BLR. Territory midpoints moved closer rather than away from the railway, albeit with variable patterns for individual sites and species. Mixed effect models showed no differences in avian biodiversity between the Construction, Ready and Traffic phases compared with Before, but relative increases in numbers of territories and decreases in territory midpoint distances to the BLR. The results do not support a general detrimental effect of railway construction on bird populations in terms of biodiversity loss, reduced abundances or shying-away from train traffic. More studies and the development of \"Railway Ecology\" are badly needed.

ecology↗

bioRxiv2018

Decrease in Microbial Diversity Along a Pollution Gradient in Citarum River Sediment

Pollution of water resources is a major risk to human health and water quality throughout the world. Here, we studied the effect of river pollution on the microbial community composition in the Citarum River Basin, West Java, Indonesia. Sediment was collected at six sampling points along a gradient of pollution, from the pristine source of the river to the heavily polluted downstream site in the densely populated urban area of Bandung. After DNA extraction, microbial diversity and potential for nitrogen cycling were analyzed based on 16S rRNA gene amplicon sequencing and metagenomics. Comparing the pristine sediment to the polluted site showed a lower microbial diversity and higher dominance of anaerobic processes than at the polluted site. The most dominant phylum within the Bacteria were the Proteobacteria, which shifted from Beta- and Deltaproteobacteria in the pristine site to Alpha- and Gammaproteobacteria in the polluted sediment. With pollution Actinobacteria, Bacteroidetes, and Firmicutes increased in relative abundance. Relative high abundance of Soil Crenarchaeotic group was found in all sample sites, whilst the methanogenic archaea became more abundant with increased pollution and anaerobicity. The study of the nitrogen cycling potential revealed that ammonium oxidation and denitrification appeared to be abundant processes in the pristine site, whereas ammonification seemed to be more important in the polluted site. Increased water treatment would restore water quality and microbial diversity in Citarum river sediments.

microbiology↗

bioRxiv2017

Glucose limitation in Lactococcus shapes a single-peaked fitness landscape exposing membrane occupancy as a constraint

A central theme in biology is to understand the molecular basis of fitness: which strategies succeed under which conditions; how are they mechanistically implemented; and which constraints shape trade-offs between alternative strategies. We approached these questions with parallel bacterial evolution experiments in chemostats. Chemostats provide a constant environment with a defined resource limitation (glucose), in which the growth rate can be controlled. Using Lactococcus lactis, we found a single mutation in a global regulator of carbon metabolism, CcpA, to confer predictable fitness improvements across multiple growth rates. In silico protein structural analysis complemented with biochemical and phenotypic assays, show that the mutation reprograms the CcpA regulon, specifically targeting transporters. This supports that membrane occupancy, rather than biosynthetic capacity, is the dominant constraint for the observed fitness enhancement. It also demonstrates that cells can modulate a pleiotropic regulator to work around limiting constraints.

genomics↗