Biology subjects

Andersson, B.

Publications and source records attributed to Andersson, B..

13 recordsLinked to original sources

bioRxiv2026

Comprehensive genomic analysis of Trypanosoma rangeli reveals key insights into the biology and evolution of this non-virulent American mammalian trypanosome

BackgroundTrypanosoma rangeli is a non-virulent hemoflagellate protozoan parasite that infects mammals, including humans, in Central and South America. It is primarily transmitted through the bites of triatomine bugs and shares an overlapping geographical distribution with T. cruzi, as well as triatomine vectors and mammalian hosts, and various shared surface antigens. The life cycle of T. rangeli differs from those of other human-infecting trypanosomes, such as T. cruzi and T. brucei, and the molecular mechanisms underlying host-parasite and host-vector interactions are not well understood, demanding improved molecular and genomic resources. ResultsThe use of a hybrid approach to sequence and assemble the T. rangeli genome, complemented by transcriptomics and proteomics for functional gene annotation, led to the generation of the near-complete genome sequence of the parasite. Detailed intra- and inter-specific comparative genomics allowed analysis of polymorphisms, genome structure and improved resolution of genes coding for important surface molecules such as Mucins, TASV and GP63. ConclusionsThe improved T. rangeli genome assembly, combined with comparative genomics has yielded novel biological insights. These included the first description of a metalloprotease activity, attributed to specific GP63 genes that are absent in Leishmania species. In addition, a TASV gene family that is absent in T. cruzi was identified, which indicates a possible role in the T. rangeli infection process.

microbiology↗

bioRxiv2025

TNF-α-Driven Systemic Inflammasome Hyperactivity Links Psoriatic Inflammation to monocyte inflammatory response and platelet activation

BackgroundPsoriasis is a chronic skin disease mediated by Th1 and Th17 immune responses and is classified as a systemic inflammatory disorder. Notably, psoriasis is an independent risk factor for myocardial infarction, stroke, and cardiovascular mortality, particularly in severe disease. However, the cellular mechanisms linking psoriasis to cardiovascular disease risk have not yet been identified. To address this gap, we investigated systemic markers of inflammasome signaling and innate immune activation in patients with psoriasis. MethodsWhole blood was collected from 43 patients, including active psoriasis (mild-to-moderate disease) without clinical manifestations of atherosclerosis, inactive psoriasis (minimal disease activity), patients receiving anti-TNF- therapy, and 19 BMI-matched healthy controls. Multiparametric spectral flow cytometry was performed to profile inflammasome signaling, and mass spectrometry-based proteomics was used to obtain unbiased phenotyping of circulating immune cells. ResultsClassical monocytes from patients with active psoriasis exhibited heightened NLRP3 protein expression and caspase-1 activity upon brief physiological stimulation, responses absent in inactive psoriasis and healthy controls. Mechanistically, active psoriasis demonstrated elevated plasma ATP and increased monocyte expression of P2X7R, a potent NLRP3 activator. TNF- was identified as a key cytokine, selectively upregulating both P2X7R and NLRP3. Baseline proteomics revealed enriched pathways for monocyte extravasation and cell adhesion, suggesting a pro-thrombotic state. Stimulation increased proteins linked to ROS and mitochondrial stress. Monocytes from active psoriasis exhibited increased baseline activation and, upon stimulation, enhanced monocyte-platelet aggregation, both of which were attenuated by inhibition of mitochondrial ROS. Importantly, anti-TNF therapy normalized ATP levels, P2X7R expression, inflammasome responsiveness, monocyte activation, and monocyte-platelet interactions, supporting the restoration of systemic immune homeostasis. ConclusionsIn patients with mild-to-moderate psoriasis, we demonstrate persistent systemic stress, resulting in inflammasome hyperreactivity and increased monocyte-platelet aggregation in response to minor perturbations in cellular homeostasis. Notably, TNF- blockade restores these effects, providing mechanistic insight into how anti-TNF therapy reduces systemic inflammation and cardiovascular risk. What is already known about this topic?O_LIPsoriasis is a systemic, immune-mediated skin disease that is associated with an increased risk of cardiovascular disease (CVD), particularly in severe disease. C_LIO_LIThe NLRP3 inflammasome, an innate immune sensor, has been implicated in the pathogenesis of CVD. C_LIO_LIAnti-TNF therapy, which is effective in treating psoriasis, is proposed to reduce CVD risk, but the underlying mechanisms remain unclear. C_LI What does this study add?O_LIPatients with mild-to-moderate psoriasis without clinical manifestations of atherosclerosis demonstrate elevated plasma ATP levels, increased monocyte P2X7 receptor expression, and enriched pathways for monocyte activation and extravasation, suggesting persistent systemic stress. C_LIO_LIMonocytes from these patients display ROS-dependent hyperactivation of the NLRP3 inflammasome and increased formation of monocyte-platelet aggregates in response to minor perturbations in cellular homeostasis. C_LIO_LITNF- was identified as a key cytokine, selectively upregulating both P2X7R and NLRP3. C_LIO_LIAnti-TNF therapy normalized these aberrant immune responses, suggesting a mechanism for its proposed cardioprotective effects. C_LI Novelty and significanceThis study provides evidence that patients with mild to moderate psoriasis, without clinical manifestations of atherosclerosis, exhibit concurrent elevations in plasma ATP levels, monocyte P2X7 receptor expression, inflammasome responsiveness, and monocyte-platelet aggregates: features increasingly associated with CVD risk. These findings suggest that dysregulated purinergic signaling may contribute to systemic immune activation in psoriasis. Importantly, anti-TNF therapy was associated with normalization of these parameters, pointing toward a potential immunomodulatory mechanism by which such treatment may help reduce CVD risk. These observations highlight a novel intersection between inflammation, purinergic signaling, and monocyte-platelet activation, which may contribute to the increased CVD risk in psoriasis.

immunology↗

bioRxiv2023

Bamboozle: A bioinformatic tool for identification and quantification of intraspecific barcodes

Evolutionary changes in populations of microbes, such as microalgae, cannot be traced using conventional metabarcoding loci as they lack intraspecific resolution. Consequently, selection and competition processes amongst strains of the same species cannot be resolved without elaborate isolation, culturing, and genotyping efforts. Bamboozle, a new bioinformatic tool introduced here, scans a species entire genome and identifies allele-rich barcodes that enable direct identification of different strains from a common population, and a single DNA sample, using amplicon sequencing. We demonstrate its usefulness by identifying hypervariable barcoding loci (<500 bp) from genomic data in two microalgal species, the diploid diatom Skeletonema marinoi, and the haploid chlorophyte Chlamydomonas reinhardtii. Across the genomes, only 26 loci capable of resolving all available strains genotypes were identified, all of which are within protein-coding genes of variable metabolic function. Single nucleotide polymorphisms (SNPs) provided the most reliable genetic markers, and amongst 55 strains of S. marinoi, three 500 bp loci contained, on average, 46 SNPs, 103 unique alleles, and displayed 100% heterozygosity. The prevalence of heterozygosity was identified as a novel opportunity to improve strain quantification and detect false positive artefacts during denoising of amplicon sequences. Finally, we illustrate how metabarcoding of a single genetic locus can be used to track strain abundances of 58 strains of S. marinoi in an artificial selection experiment. As future genomics datasets become available and DNA sequencing technologies develop, Bamboozle has flexible user settings enabling optimal barcodes to be designed for other species and applications.

evolutionary biology↗

bioRxiv2021

Identification of antibiotic resistance proteins via MiCId's augmented workflow. A mass spectrometry-based proteomics approach

Fast and accurate identifications of pathogenic bacteria along with their associated antibiotic resistance proteins are of paramount importance for patient treatments and public health. While mass spectrometry has become an important, technique for diagnostics of infectious disease, there is a need for mass spectrometry workflows offering this capability. To meet this need, we have augmented the previously published Microorganism Classification and Identification (MiCId) workflow for this capability. To evaluate the performance of the newly augmented MiCId workflow, we have used MS/MS datafiles from samples of 10 antibiotic resistance bacterial strains belonging to three different species: Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The evaluation results show that MiCIds workflow has a sensitivity value around 85% (with a lower bound at about 72%) and a precision greater than 95% in the identification of antibiotic resistance proteins. Using MS/MS datasets from samples of two bacterial clonal isolates, one being antibiotic-sensitive while the other (obtained from the same patient at different times) being multidrug-resistant, we applied MiCIds workflow to investigate possible mechanisms of antibiotic resistance in these pathogenic bacteria; the results showed that MiCIds conclusions are in agreement with the published study. Furthermore, we show that MiCIds workflow is fast. It pro-vides microorganismal identifications, protein identifications, sample biomass estimates, and antibiotic resistance protein identifications in 6-17 minutes per MS/MS sample using computing resources that are available in most desktop and laptop computers, making it a highly portable workflow. This study demonstrated that MiCIds workflow is fast, portable, and with high sensitivity and high precision, making it a valuable tool for rapid identifications of bacteria as well as detection of their antibiotic resistance proteins. The new version of MiCId (v.07.01.2021) is freely available for download at https://www.ncbi.nlm.nih.gov/CBBresearch/Yu/downloads.html.

systems biology↗

bioRxiv2021

Experimental microevolution of Trypanosoma cruzi reveals hybridization and clonal mechanisms driving rapid diversification of genome sequence and structure.

Protozoa and fungi are known to have extraordinarily diverse mechanisms of genetic exchange. However, the presence and epidemiological relevance of genetic exchange in Trypanosoma cruzi, the agent of Chagas disease, has been controversial and debated for many years. Field studies have identified both predominantly clonal and sexually recombining natural populations. Two of six natural T. cruzi lineages (TcV and TcVI) show hybrid mosaicism, using analysis of single-gene locus markers. The formation of hybrid strains in vitro has been achieved and this provides a framework to study the mechanisms and adaptive significance of genetic exchange. Using whole genome sequencing of a set of experimental hybrids strains, we have confirmed that hybrid formation initially results in tetraploid parasites. The hybrid progeny showed novel mutations that were not attributable to either (diploid) parent showing an increase in amino acid changes. In long-term culture, up to 800 generations, there was progressive, gradual erosion of progeny genomes towards triploidy, yet retention of elevated copy number was observed at several core housekeeping loci. Our findings indicate hybrid formation by fusion of diploid T. cruzi, followed by sporadic genome erosion, but with substantial potential for adaptive evolution, as has been described as a genetic feature of other organisms, such as some fungi.

microbiology↗

bioRxiv2021

High genome plasticity and frequent genetic exchange in Leishmania tropica isolates from Afghanistan, Iran and Syria

BackgroundThe kinetoplastid protozoan Leishmania tropica mainly causes cutaneous leishmaniasis in humans in the Middle East, and relapse or treatment failure after treatment are common in this area. L. tropicas digenic life cycle includes distinct stages in the vector sandfly and the mammalian host. Sexual reproduction and genetic exchange appear to occur more frequently than in other Leishmania species. Understanding these processes is complicated by chromosome instability during cell division that yields aneuploidy, recombination and heterozygosity. This combination of rare recombination and aneuploid permits may reveal signs of hypothetical parasexual mating, where diploid cells fuse to form a transient tetraploid that undergoes chromosomal recombination and gradual chromosomal loss. Methodology/Principal FindingsThe genome-wide SNP diversity from 22 L. tropica isolates showed chromosome-specific runs of patchy heterozygosity and extensive chromosome copy number variation. All these isolates were collected during 2007-2017 in Sweden from patients infected in the Middle East and included isolates from a patient possessing two genetically distinct leishmaniasis infections three years apart with no evidence of re-infection. We found differing ancestries on the same chromosome (chr36) across multiple samples: matching the reference genome with few derived alleles, followed by blocks of heterozygous SNPs, and then by clusters of homozygous SNPs with specific recombination breakpoints at an inferred origin of replication. Other chromosomes had similar marked changes in heterozygosity at strand-switch regions separating polycistronic transcriptional units. Conclusion/SignificanceThese large-scale intra- and inter-chromosomal changes in diversity driven by recombination and aneuploidy suggest multiple mechanisms of cell reproduction and diversification in L. tropica, including mitotic, meiotic and parasexual processes. It underpins the need for more genomic surveillance of Leishmania, to detect emerging hybrids that could spread more widely and to better understand the association between genetic variation and treatment outcome. Furthering our understanding of Leishmania genome evolution and ancestry will aid better diagnostics and treatment for cutaneous leishmaniasis caused by L.tropica in the Middle East. Author SummaryCutaneous leishmaniasis is mainly caused by Leishmania tropica in the Middle East, where it is known for treatment failure and a need for prolonged and/or multiple treatments. Several factors affect the clinical presentation and treatment outcome, such as host genetic variability and specific immune response, as well as environmental factors and the vector species. Little is known about the parasite genome and its influence on treatment response. By analysing the genome of 22 isolates of L. tropica, we have revealed extensive genomic variation and a complex population structure with evidence of genetic exchange within and among the isolates, indicating a possible presence of sexual or parasexual mechanisms. Understanding the Leishmania genome better may improve future treatment and better understanding of treatment failure and relapse.

genetics↗

bioRxiv2021

The genomic basis of domestic colonisation and dispersal in Chagas disease vectors

The biology of vector adaptation to the human habitat remains poorly understood for many arthropod-borne diseases but underpins effective and sustainable disease control. We adopted a landscape genomics approach to investigate gene flow, signatures of local adaptation, and drivers of population structure among multiple linked wild and domestic population pairs in Rhodnius ecuadoriensis, an important vector of Chagas Disease. Evidence of high triatomine gene flow (FST) between wild and domestic ecotopes at sites throughout the study area indicate insecticide-based control will be hindered by constant re-infestation of houses. Genome scans revealed genetic loci with strong signal of local adaptation to the domestic setting, which we mapped to annotated regions in the Rhodnius prolixus genome. Our landscape genomic mixed effects models showed Rhodnius ecuadoriensis population structure and connectivity is driven by landscape elevation at a regional scale. Our ecologically- and spatially-explicit vector dispersal model enables targeted vector control and recommends spatially discrete, periodic interventions to local authorities as more efficacious than current, haphazard approaches. In tandem, evidence for parallel genomic adaptation to colonisation of the domestic environment at multiple sites sheds new light on the evolutionary basis of adaptation to the human host in arthropod vectors.

genomics↗

bioRxiv2020

SARS-CoV-2 genome sequences from late April in Stockholm, Sweden reveal a novel mutation in the spike protein

Large research efforts are going into characterizing, mapping the spread, and studying the biology and clinical features of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we report four complete SARS-CoV-2 genome sequences obtained from patients confirmed to have the disease in Stockholm, Sweden, in late April. A variant at position 23463 was found for the first time in one genome. It changes an arginine (R) residue to histidine (H) at position 364 in the S1 subunit of the spike protein. The genomes belonged to two different genetic groups, previously reported as two of the three main genetic groups found in Sweden. Three of them are from group B.1/G, corresponding to the Italian outbreak, reported by the Public Health Agency of Sweden to have declined in prevalence by late April, and more investigation is needed in order to ensure that the spread of different types of SARS-CoV-2 is fully characterized. HighlightsO_LIFour near-complete genomes of SARS-CoV-2 were assembled from late April in Stockholm. C_LIO_LIA novel mutation in the spike protein were found. C_LIO_LIThe phylogeny of the strains were discussed. C_LI

bioinformatics↗

bioRxiv2020

Activation of a neural stem cell transcriptional program in parenchymal astrocytes

Neural stem cells, located in discrete niches in the adult brain, generate new neurons throughout life. These stem cells are specialized astrocytes, but astrocytes in other brain regions do not generate neurons under physiological conditions. After stroke, however, striatal astrocytes undergo neurogenesis in mice, triggered by decreased Notch signaling. We used single-cell RNA sequencing to characterize neurogenesis by Notch-depleted striatal astrocytes in vivo. Striatal astrocytes were located upstream of neural stem cells in the neuronal lineage. As astrocytes initiated neurogenesis, they became transcriptionally very similar to subventricular zone stem cells and progressed through a nearly identical neurogenic program. Surprisingly, in the non- neurogenic cortex, Notch-depleted astrocytes also initiated neurogenesis. Yet, the cortical astrocytes, and many striatal ones, stalled before entering transit- amplifying divisions. Infusion of epidermal growth factor enabled stalled striatal astrocytes to resume neurogenesis. We conclude that parenchymal astrocytes are latent neural stem cells and that targeted interventions can guide them through their neuronal differentiation.

neuroscience↗

bioRxiv2019

Clonally distinct differentiation trajectories shape CD8+ memory T cell heterogeneity after acute viral infections in humans

CD8+ T cells play essential roles in immunity to viral and bacterial infections, and to guard against malignant cells. The CD8+ T cell response to an antigen is composed of many T cell clones with unique T cell receptors, together forming a heterogenous repertoire of phenotypically and functionally distinct effector and memory cells1, 2. How individual T cell clones contribute to this heterogeneity during an immune response is key to understand immunity but remains largely unknown. Here, we longitudinally tracked CD8+ T cell clones expanding in response to yellow fever virus vaccination at the single cell level in humans. We show that only a fraction of the clones detected in the acute response persists as circulating memory T cells, indicative of clonal selection. Clones persisting in the memory phase displayed biased differentiation trajectories along a gradient of stem cell memory (SCM) towards terminally differentiated effector memory (EMRA) fates. Reactivation of single memory CD8+ T cells revealed that they were poised to recapitulate skewed differentiation trajectories in secondary responses, and this was generalizable across individuals for both yellow fever and influenza virus. Together, we show that the sum of distinct clonal differentiation repertoires results in the multifaceted T cell response to acute viral infections in humans.

immunology↗

bioRxiv2019

Completing Linnaeus’s Inventory of the Swedish Insect Fauna: Only 5000 Species Left

Despite more than 250 years of taxonomic research, we still have only a vague idea about the true size and composition of the faunas and floras of the planet. Many biodiversity inventories provide limited insight because they focus on a small taxonomic subsample or a tiny geographic area. Here, we report on the size and composition of the Swedish insect fauna, thought to represent roughly half of the diversity of multicellular life in one of the largest European countries. Our results are based on more than a decade of data from the Swedish Taxonomy Initiative and its massive inventory of the countrys insect fauna, the Swedish Malaise Trap Project The fauna is considered one of the best known in the world, but the initiative has nevertheless revealed a surprising amount of hidden diversity: more than 3,000 new species (301 new to science) have been documented so far. Here, we use three independent methods to analyze the true size and composition of the fauna at the family or subfamily level: (1) assessments by experts who have been working on the most poorly known groups in the fauna; (2) estimates based on the proportion of new species discovered in the Malaise trap inventory; and (3) extrapolations based on species abundance and incidence data from the inventory. For the last method, we develop a new estimator, the combined non-parametric estimator, which we show is less sensitive to poor coverage of the species pool than other popular estimators. The three methods converge on similar estimates of the size and composition of the fauna, suggesting that it comprises around 33,000 species. Of those, 8,600 (26%) were unknown at the start of the inventory and 5,000 (15%) still await discovery. We analyze the taxonomic and ecological composition of the estimated fauna, and show that most of the new species belong to Hymenoptera and Diptera groups that are decomposers or parasitoids. Thus, current knowledge of the Swedish insect fauna is strongly biased taxonomically and ecologically, and we show that similar but even stronger biases have distorted our understanding of the fauna in the past. We analyze latitudinal gradients in the size and composition of known European insect faunas and show that several of the patterns contradict the Swedish data, presumably due to similar knowledge biases. Addressing these biases is critical in understanding insect biomes and the ecosystem services they provide. Our results emphasize the need to broaden the taxonomic scope of current insect monitoring efforts, a task that is all the more urgent as recent studies indicate a possible worldwide decline in insect faunas.

ecology↗

bioRxiv2018

Parallel sexual and parasexual population genomic structure in Trypanosoma cruzi

Genetic exchange and hybridization in parasitic organisms is fundamental to the exploitation of new hosts and host populations. Variable mating frequency often coincides with strong metapopulation structure, where patchy selection or demography may favor different reproductive modes. Evidence for genetic exchange in Trypanosoma cruzi over the last 30 years has been limited and inconclusive. The reproductive modes of other medically important trypanosomatids are better established, although little is known about their variability on a spatio-temporal scale. Targeting a contemporary focus of T. cruzi transmission in southern Ecuador, we present compelling evidence from 45 sequenced genomes that T. cruzi (discrete typing unit I) maintains sexual populations alongside others that represent clonal bursts of parasexual origin. Strains from one site exhibit genome-wide Hardy-Weinberg equilibrium and intra-chromosomal linkage decay consistent with meiotic reproduction. Strains collected from adjacent areas (>6 km) show excess heterozygosity, near-identical haplo-segments, common mitochondrial sequences and levels of aneuploidy incompatible with Mendelian sex. Certain individuals exhibit trisomy in as many as fifteen chromosomes. Others present fewer, yet shared, aneuploidies reminiscent of mitotic genome erosion and parasexual genetic exchange. Genomic and intra-genomic phylogenetics as well as haplotype co-ancestry analyses indicate a clear break in gene-flow between these distinct populations, despite the fact that they occasionally co-occur in vectors and hosts. We propose biological explanations for the fine-scale disconnectivity we observe and discuss the epidemiological consequences of flexible reproductive modes and their genomic architecture for this medically important parasite.

evolutionary biology↗

bioRxiv2018

Repeat-driven generation of antigenic diversity in a major human pathogen, Trypanosoma cruzi

Trypanosoma cruzi, a zoonotic kinetoplastid protozoan with a complex genome, is the causative agent of American trypanosomiasis (Chagas disease). The parasite uses a highly diverse repertoire of surface molecules, with roles in cell invasion, immune evasion and pathogenesis. Thus far, the genomic regions containing these genes have been impossible to resolve and it has been impossible to study the structure and function of the several thousand repetitive genes encoding the surface molecules of the parasite. We here present an improved genome assembly of a T. cruzi clade I (TcI) strain using high coverage PacBio single molecule sequencing, together with Illumina sequencing of 34 T. cruzi TcI isolates and clones from different geographic locations, sample sources and clinical outcomes. Resolution of the surface molecule gene structure reveals an unusual duality in the organisation of the parasite genome, a core genomic region syntenous with related protozoa flanked by unique and highly plastic subtelomeric regions encoding surface antigens. The presence of abundant interspersed retrotransposons in the subtelomeres suggests that these elements are involved in a recombination mechanism for the generation of antigenic variation and evasion of the host immune response. The comparative genomic analysis of the cohort of TcI strains revealed multiple cases of such recombination events involving surface molecule genes and has provided new insights into T. cruzi population structure.

genomics↗