BMC Biology

Journal: BMC Biology

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BMC Biol

Publisher

BioMed Central

ISSN

1741-7007

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Publications 1 - 10 of 33

A 19-isolate reference-quality global pangenome for the fungal wheat pathogen Zymoseptoria tritici
Badet, Thomas; Oggenfuss, Ursula; Abraham, Leen; et al. (2020)
BMC Biology
Background The gene content of a species largely governs its ecological interactions and adaptive potential. A species is therefore defined by both core genes shared between all individuals and accessory genes segregating presence-absence variation. There is growing evidence that eukaryotes, similar to bacteria, show intra-specific variability in gene content. However, it remains largely unknown how functionally relevant such a pangenome structure is for eukaryotes and what mechanisms underlie the emergence of highly polymorphic genome structures. Results Here, we establish a reference-quality pangenome of a fungal pathogen of wheat based on 19 complete genomes from isolates sampled across six continents. Zymoseptoria tritici causes substantial worldwide losses to wheat production due to rapidly evolved tolerance to fungicides and evasion of host resistance. We performed transcriptome-assisted annotations of each genome to construct a global pangenome. Major chromosomal rearrangements are segregating within the species and underlie extensive gene presence-absence variation. Conserved orthogroups account for only ~ 60% of the species pangenome. Investigating gene functions, we find that the accessory genome is enriched for pathogenesis-related functions and encodes genes involved in metabolite production, host tissue degradation and manipulation of the immune system. De novo transposon annotation of the 19 complete genomes shows that the highly diverse chromosomal structure is tightly associated with transposable element content. Furthermore, transposable element expansions likely underlie recent genome expansions within the species. Conclusions Taken together, our work establishes a highly complex eukaryotic pangenome providing an unprecedented toolbox to study how pangenome structure impacts crop-pathogen interactions.
Pangenome analyses of the wheat pathogen Zymoseptoria tritici reveal the structural basis of a highly plastic eukaryotic genome
Plissonneau, Clémence; Hartmann, Fanny E.; Croll, Daniel (2018)
BMC Biology
Background: Structural variation contributes substantially to polymorphism within species. Chromosomal rearrangements that impact genes can lead to functional variation among individuals and influence the expression of phenotypic traits. Genomes of fungal pathogens show substantial chromosomal polymorphism that can drive virulence evolution on host plants. Assessing the adaptive significance of structural variation is challenging, because most studies rely on inferences based on a single reference genome sequence. Results: We constructed and analyzed the pangenome of Zymoseptoria tritici, a major pathogen of wheat that evolved host specialization by chromosomal rearrangements and gene deletions. We used single-molecule real-time sequencing and high-density genetic maps to assemble multiple genomes. We annotated the gene space based on transcriptomics data that covered the infection life cycle of each strain. Based on a total of five telomere-to-telomere genomes, we constructed a pangenome for the species and identified a core set of 9149 genes. However, an additional 6600 genes were exclusive to a subset of the isolates. The substantial accessory genome encoded on average fewer expressed genes but a larger fraction of the candidate effector genes that may interact with the host during infection. We expanded our analyses of the pangenome to a worldwide collection of 123 isolates of the same species. We confirmed that accessory genes were indeed more likely to show deletion polymorphisms and loss-of-function mutations compared to core genes. Conclusions: The pangenome construction of a highly polymorphic eukaryotic pathogen showed that a single reference genome significantly underestimates the gene space of a species. The substantial accessory genome provides a cradle for adaptive evolution.
The role of vegetative cell fusions in the development and asexual reproduction of the wheat fungal pathogen Zymoseptoria tritici
Sardinha Francisco, Carolina; Zwyssig, Maria M.; Palma-Guerrero, Javier (2020)
BMC Biology
Background The ability of fungal cells to undergo cell-to-cell communication and anastomosis, the process of vegetative hyphal fusion, allows them to maximize their overall fitness. Previous studies in a number of fungal species have identified the requirement of several signaling pathways for anastomosis, including the so far best characterized soft (So) gene, and the MAPK pathway components MAK-1 and MAK-2 of Neurospora crassa. Despite the observations of hyphal fusions’ involvement in pathogenicity and host adhesion, the connection between cell fusion and fungal lifestyles is still unclear. Here, we address the role of anastomosis in fungal development and asexual reproduction in Zymoseptoria tritici, the most important fungal pathogen of wheat in Europe. Results We show that Z. tritici undergoes self-fusion between distinct cellular structures, and its mechanism is dependent on the initial cell density. Contrary to other fungi, cell fusion in Z. tritici only resulted in cytoplasmic mixing but not in multinucleated cell formation. The deletion of the So orthologous ZtSof1 disrupted cell-to-cell communication affecting both hyphal and germling fusion. We show that Z. tritici mutants for MAPK-encoding ZtSlt2 (orthologous to MAK-1) and ZtFus3 (orthologous to MAK-2) genes also failed to undergo anastomosis, demonstrating the functional conservation of this signaling mechanism across species. Additionally, the ΔZtSof1 mutant was severely impaired in melanization, suggesting that the So gene function is related to melanization. Finally, we demonstrated that anastomosis is dispensable for pathogenicity, but essential for the pycnidium development, and its absence abolishes the asexual reproduction of Z. tritici. Conclusions We demonstrate the role for ZtSof1, ZtSlt2, and ZtFus3 in cell fusions of Z. tritici. Cell fusions are essential for different aspects of the Z. tritici biology, and the ZtSof1 gene is a potential target to control septoria tritici blotch (STB) disease.
Cell lineage branching as a strategy for proliferative control
Buzi, Gentian; Lander, Arthur D.; Khammash, Mustafa Hani (2015)
BMC Biology
Background How tissue and organ sizes are specified is one of the great unsolved mysteries in biology. Experiments and mathematical modeling implicate feedback control of cell lineage progression, but a broad understanding of what lineage feedback accomplishes is lacking. Results By exploring the possible effects of various biologically relevant disturbances on the dynamic and steady state behaviors of stem cell lineages, we find that the simplest and most frequently studied form of lineage feedback - which we term renewal control - suffers from several serious drawbacks. These reflect fundamental performance limits dictated by universal conservation-type laws, and are independent of parameter choice. Here we show that introducing lineage branches can circumvent all such limitations, permitting effective attenuation of a wide range of perturbations. The type of feedback that achieves such performance - which we term fate control - involves promotion of lineage branching at the expense of both renewal and (primary) differentiation. We discuss the evidence that feedback of just this type occurs in vivo, and plays a role in tissue growth control. Conclusions Regulated lineage branching is an effective strategy for dealing with disturbances in stem cell systems. The existence of this strategy provides a dynamics-based justification for feedback control of cell fate in vivo.
The diversity of reproductive parasites among arthropods: Wolbachiado not walk alone
Duron, Olivier; Bouchon, Didier; Boutin, Sébastien; et al. (2008)
BMC Biology
Background Inherited bacteria have come to be recognised as important components of arthropod biology. In addition to mutualistic symbioses, a range of other inherited bacteria are known to act either as reproductive parasites or as secondary symbionts. Whilst the incidence of the α-proteobacterium Wolbachia is relatively well established, the current knowledge of other inherited bacteria is much weaker. Here, we tested 136 arthropod species for a range of inherited bacteria known to demonstrate reproductive parasitism, sampling each species more intensively than in past surveys. Results The inclusion of inherited bacteria other than Wolbachia increased the number of infections recorded in our sample from 33 to 57, and the proportion of species infected from 22.8% to 32.4%. Thus, whilst Wolbachia remained the dominant inherited bacterium, it alone was responsible for around half of all inherited infections of the bacteria sampled, with members of the Cardinium, Arsenophonus and Spiroplasma ixodetis clades each occurring in 4% to 7% of all species. The observation that infection was sometimes rare within host populations, and that there was variation in presence of symbionts between populations indicates that our survey will itself underscore incidence. Conclusion This extensive survey demonstrates that at least a third of arthropod species are infected by a diverse assemblage of maternally inherited bacteria that are likely to strongly influence their hosts' biology, and indicates an urgent need to establish the nature of the interaction between non-Wolbachia bacteria and their hosts.
Native-like membrane models of E. coli polar lipid extract shed light on the importance of lipid composition complexity
Pluhackova, Kristyna; Horner, Andreas (2021)
BMC Biology
Background Lipid-protein interactions stabilize protein oligomers, shape their structure, and modulate their function. Whereas in vitro experiments already account for the functional importance of lipids by using natural lipid extracts, in silico methods lack behind by embedding proteins in single component lipid bilayers. However, to accurately complement in vitro experiments with molecular details at very high spatio-temporal resolution, molecular dynamics simulations have to be performed in natural(-like) lipid environments. Results To enable more accurate MD simulations, we have prepared four membrane models of E. coli polar lipid extract, a typical model organism, each at all-atom (CHARMM36) and coarse-grained (Martini3) representations. These models contain all main lipid headgroup types of the E. coli inner membrane, i.e., phosphatidylethanolamines, phosphatidylglycerols, and cardiolipins, symmetrically distributed between the membrane leaflets. The lipid tail (un)saturation and propanylation stereochemistry represent the bacterial lipid tail composition of E. coli grown at 37∘C until 3/4 of the log growth phase. The comparison of the Simple three lipid component models to the complex 14-lipid component model Avanti over a broad range of physiologically relevant temperatures revealed that the balance of lipid tail unsaturation and propanylation in different positions and inclusion of lipid tails of various length maintain realistic values for lipid mobility, membrane area compressibility, lipid ordering, lipid volume and area, and the bilayer thickness. The only Simple model that was able to satisfactory reproduce most of the structural properties of the complex Avanti model showed worse agreement of the activation energy of basal water permeation with the here performed measurements. The Martini3 models reflect extremely well both experimental and atomistic behavior of the E. coli polar lipid extract membranes. Aquaporin-1 embedded in our native(-like) membranes causes partial lipid ordering and membrane thinning in its vicinity. Moreover, aquaporin-1 attracts and temporarily binds negatively charged lipids, mainly cardiolipins, with a distinct cardiolipin binding site in the crevice at the contact site between two monomers, most probably stabilizing the tetrameric protein assembly. Conclusions The here prepared and validated membrane models of E. coli polar lipids extract revealed that lipid tail complexity, in terms of double bond and cyclopropane location and varying lipid tail length, is key to stabilize membrane properties over a broad temperature range. In addition, they build a solid basis for manifold future simulation studies on more realistic lipid membranes bridging the gap between simulations and experiments.
Diversity across organisational scale emerges through dispersal ability and speciation dynamics in tropical fish
Keggin, Thomas; Waldock, Conor; Skeels, Alexander; et al. (2023)
BMC Biology
Background: Biodiversity exists at different levels of organisation: e.g. genetic, individual, population, species, and community. These levels of organisation all exist within the same system, with diversity patterns emerging across organisational scales through several key processes. Despite this inherent interconnectivity, observational studies reveal that diversity patterns across levels are not consistent and the underlying mechanisms for variable continuity in diversity across levels remain elusive. To investigate these mechanisms, we apply a spatially explicit simulation model to simulate the global diversification of tropical reef fishes at both the population and species levels through emergent population-level processes. Results: We find significant relationships between the population and species levels of diversity which vary depending on both the measure of diversity and the spatial partitioning considered. In turn, these population-species relationships are driven by modelled biological trait parameters, especially the divergence threshold at which populations speciate. Conclusions: To explain variation in multi-level diversity patterns, we propose a simple, yet novel, population-to-species diversity partitioning mechanism through speciation which disrupts continuous diversity patterns across organisational levels. We expect that in real-world systems this mechanism is driven by the molecular dynamics that determine genetic incompatibility, and therefore reproductive isolation between individuals. We put forward a framework in which the mechanisms underlying patterns of diversity across organisational levels are universal, and through this show how variable patterns of diversity can emerge through organisational scale.
Deficient DNA base-excision repair in the forebrain leads to a sex-specific anxiety-like phenotype in mice
Mueller, Flavia S.; Amport, René; Notter, Tina; et al. (2022)
BMC Biology
Background Neuropsychiatric disorders, such as schizophrenia (SZ) and autism spectrum disorder (ASD), are common, multi-factorial and multi-symptomatic disorders. Ample evidence implicates oxidative stress, deficient repair of oxidative DNA lesions and DNA damage in the development of these disorders. However, it remains unclear whether insufficient DNA repair and resulting DNA damage are causally connected to their aetiopathology, or if increased levels of DNA damage observed in patient tissues merely accumulate as a consequence of cellular dysfunction. To assess a potential causal role for deficient DNA repair in the development of these disorders, we behaviourally characterized a mouse model in which CaMKIIa-Cre-driven postnatal conditional knockout (KO) of the core base-excision repair (BER) protein XRCC1 leads to accumulation of unrepaired DNA damage in the forebrain. Results CaMKIIa-Cre expression caused specific deletion of XRCC1 in the dorsal dentate gyrus (DG), CA1 and CA2 and the amygdala and led to increased DNA damage therein. While motor coordination, cognition and social behaviour remained unchanged, XRCC1 KO in the forebrain caused increased anxiety-like behaviour in males, but not females, as assessed by the light–dark box and open field tests. Conversely, in females but not males, XRCC1 KO caused an increase in learned fear-related behaviour in a cued (Pavlovian) fear conditioning test and a contextual fear extinction test. The relative density of the GABA(A) receptor alpha 5 subunit (GABRA5) was reduced in the amygdala and the dorsal CA1 in XRCC1 KO females, whereas male XRCC1 KO animals exhibited a significant reduction of GABRA5 density in the CA3. Finally, assessment of fast-spiking, parvalbumin-positive (PV) GABAergic interneurons revealed a significant increase in the density of PV+ cells in the DG of male XRCC1 KO mice, while females remained unchanged. Conclusions Our results suggest that accumulation of unrepaired DNA damage in the forebrain alters the GABAergic neurotransmitter system and causes behavioural deficits in relation to innate and learned anxiety in a sex-dependent manner. Moreover, the data uncover a previously unappreciated connection between BER deficiency, unrepaired DNA damage in the hippocampus and a sex-specific anxiety-like phenotype with implications for the aetiology and therapy of neuropsychiatric disorders.
Optimization of the antimicrobial peptide Bac7 by deep mutational scanning
Koch, Philipp; Schmitt, Steven; Heynisch, Alexander; et al. (2022)
BMC Biology
Background Intracellularly active antimicrobial peptides are promising candidates for the development of antibiotics for human applications. However, drug development using peptides is challenging as, owing to their large size, an enormous sequence space is spanned. We built a high-throughput platform that incorporates rapid investigation of the sequence-activity relationship of peptides and enables rational optimization of their antimicrobial activity. The platform is based on deep mutational scanning of DNA-encoded peptides and employs highly parallelized bacterial self-screening coupled to next-generation sequencing as a readout for their antimicrobial activity. As a target, we used Bac71-23, a 23 amino acid residues long variant of bactenecin-7, a potent translational inhibitor and one of the best researched proline-rich antimicrobial peptides. Results Using the platform, we simultaneously determined the antimicrobial activity of >600,000 Bac71-23 variants and explored their sequence-activity relationship. This dataset guided the design of a focused library of ~160,000 variants and the identification of a lead candidate Bac7PS. Bac7PS showed high activity against multidrug-resistant clinical isolates of E. coli, and its activity was less dependent on SbmA, a transporter commonly used by proline-rich antimicrobial peptides to reach the cytosol and then inhibit translation. Furthermore, Bac7PS displayed strong ribosomal inhibition and low toxicity against eukaryotic cells and demonstrated good efficacy in a murine septicemia model induced by E. coli. Conclusion We demonstrated that the presented platform can be used to establish the sequence-activity relationship of antimicrobial peptides, and showed its usefulness for hit-to-lead identification and optimization of antimicrobial drug candidates.
Emergence of wheat blast in Bangladesh was caused by a South American lineage of Magnaporthe oryzae
Islam, M. Tofazzal; Croll, Daniel; Gladieux, Pierre; et al. (2016)
BMC Biology
Background In February 2016, a new fungal disease was spotted in wheat fields across eight districts in Bangladesh. The epidemic spread to an estimated 15,000 hectares, about 16 % of the cultivated wheat area in Bangladesh, with yield losses reaching up to 100 %. Within weeks of the onset of the epidemic, we performed transcriptome sequencing of symptomatic leaf samples collected directly from Bangladeshi fields. Results Reinoculation of seedlings with strains isolated from infected wheat grains showed wheat blast symptoms on leaves of wheat but not rice. Our phylogenomic and population genomic analyses revealed that the wheat blast outbreak in Bangladesh was most likely caused by a wheat-infecting South American lineage of the blast fungus Magnaporthe oryzae. Conclusion Our findings suggest that genomic surveillance can be rapidly applied to monitor plant disease outbreaks and provide valuable information regarding the identity and origin of the infectious agent.

Publications 1 - 10 of 33

Journal: BMC Biology

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