Temporal effects and changes in the parasitic community of Prochilodus lineatus (Valenciennes, 1837) (Characiformes: Prochilodontidae) in a floodplain

The construction of dams causes several impacts on aquatic environments, altering the flow of rivers, environmental variables, and all biota present, including parasites. Little is known about how the parasitic community can be influenced in the long term by environmental changes. In this study, it was expected that the impacts caused by environmental disturbances will be directly reflected by the composition of the parasite populations. We evaluated the change in the structure of the Prochilodus lineatus endoparasite community between two periods sampled 15 years apart in the upper Paraná River floodplain. There was a significant difference in the weight–length relationship of P. lineatus between these periods and a total of 15 species of parasites were found: 11 species in Period 1 and nine species in Period 2 and five species occurred in both periods. The species richness and diversity were higher in Period 1, and we observed that the correlation of descriptors (richness, diversity and evenness) increased with fish length in this period. In both periods, digeneans numerically dominated the parasitic community, and we verified changes in the composition of parasites between periods. Both the host and the parasites were possibly affected by the environmental impacts resulting from the construction of dams over time, and it is noteworthy that complex life cycle parasites such as Digenea and Acanthocephala require intermediate hosts to complete their life cycle, and the population responds to fluctuations in the face of modified environments.

Does a complex life cycle affect adaptation to environmental change? Genome-informed insights for characterizing selection across complex life cycle

Complex life cycles, in which discrete life stages of the same organism differ in form or function and often occupy different ecological niches, are common in nature. Because stages share the same genome, selective effects on one stage may have cascading consequences through the entire life cycle. Theoretical and empirical studies have not yet generated clear predictions about how life cycle complexity will influence patterns of adaptation in response to rapidly changing environments or tested theoretical predictions for fitness trade-offs (or lack thereof) across life stages. We discuss complex life cycle evolution and outline three hypotheses—ontogenetic decoupling, antagonistic ontogenetic pleiotropy and synergistic ontogenetic pleiotropy—for how selection may operate on organisms with complex life cycles. We suggest a within-generation experimental design that promises significant insight into composite selection across life cycle stages. As part of this design, we conducted simulations to determine the power needed to detect selection across a life cycle using a population genetic framework. This analysis demonstrated that recently published studies reporting within-generation selection were underpowered to detect small allele frequency changes (approx. 0.1). The power analysis indicates challenging but attainable sampling requirements for many systems, though plants and marine invertebrates with high fecundity are excellent systems for exploring how organisms with complex life cycles may adapt to climate change.

Characterization of a MOB1 Homolog in the Apicomplexan Parasite Toxoplasma gondii

Monopolar spindle One Binder1 (MOB1) proteins are conserved components of the tumor-suppressing Hippo pathway, regulating cellular processes such as cytokinesis. Apicomplexan parasites present a life cycle that relies on the parasites’ ability to differentiate between stages and regulate their proliferation; thus, Hippo signaling pathways could play an important role in the regulation of the apicomplexan life cycle. Here, we report the identification of one MOB1 protein in the apicomplexan Toxoplasma gondii. To characterize the function of MOB1, we generated gain-of-function transgenic lines with a ligand-controlled destabilization domain, and loss-of-function clonal lines obtained through CRISPR/Cas9 technology. Contrary to what has been characterized in other eukaryotes, MOB1 is not essential for cytokinesis in T. gondii. However, this picture is complex since we found MOB1 localized between the newly individualized daughter nuclei at the end of mitosis. Moreover, we detected a significant delay in the replication of overexpressing tachyzoites, contrasting with increased replication rates in knockout tachyzoites. Finally, using the proximity-biotinylation method, BioID, we identified novel members of the MOB1 interactome, a probable consequence of the observed lack of conservation of some key amino acid residues. Altogether, the results point to a complex evolutionary history of MOB1 roles in apicomplexans, sharing properties with other eukaryotes but also with divergent features, possibly associated with their complex life cycle.

Evidence of G-Protein-Coupled Receptors (GPCR) in the Parasitic Protozoa Plasmodium falciparum—Sensing the Host Environment and Coupling within Its Molecular Signaling Toolkit

Throughout evolution, the need for single-celled organisms to associate and form a single cluster of cells has had several evolutionary advantages. In complex, multicellular organisms, each tissue or organ has a specialty and function that make life together possible, and the organism as a whole needs to act in balance and adapt to changes in the environment. Sensory organs are essential for connecting external stimuli into a biological response, through the senses: sight, smell, taste, hearing, and touch. The G-protein-coupled receptors (GPCRs) are responsible for many of these senses and therefore play a key role in the perception of the cells’ external environment, enabling interaction and coordinated development between each cell of a multicellular organism. The malaria-causing protozoan parasite, Plasmodium falciparum, has a complex life cycle that is extremely dependent on a finely regulated cellular signaling machinery. In this review, we summarize strong evidence and the main candidates of GPCRs in protozoan parasites. Interestingly, one of these GPCRs is a sensor for K+ shift in Plasmodium falciparum, PfSR25. Studying this family of proteins in P. falciparum could have a significant impact, both on understanding the history of the evolution of GPCRs and on finding new targets for antimalarials.

Global Chromosome Topology and the Two-Component Systems in Concerted Manner Regulate Transcription in Streptomyces

Streptomyces microbes, soil bacteria with complex life cycle, are the producers of a broad range of biologically active compounds (e.g., antibiotics). Streptomyces bacteria respond to various environmental signals using a complex transcriptional regulation mechanism. Understanding regulation of their gene expression is crucial for Streptomyces application as industrial organisms.

Genome-wide transcriptome analysis of the early developmental stages of Echinococcus granulosus protoscoleces reveals extensive alternative splicing events in the spliceosome pathway

Background The complex life cycle of Echinococcus granulosus involves numerous environmental conditions within different intermediate and definitive hosts. This requires adaptation at different levels of transcript regulation. Alternative splicing (AS) and the related cellular functions as one of the major fields of post-genomics has been poorly studied in tapeworms. In the present study, we investigated AS events and their potential biological effects in E. granulosus. Methods Whole transcriptome sequencing data of four groups of protoscoleces were prepared for RNA-seq library construction. Fresh protoscoleces were either used as non-induced controls (NT group) or incubated for 15 min with pepsin (PEP group) and cultivated in a biphasic medium for 12 and 24 h (12 and 24 h groups). The frequency and different types of AS events were identified using rMATS software. Functional annotations and gene ontology of differential AS (DAS) genes were performed using Blast2GO software. AS events were experimentally validated by PCR on the protoscolex cDNAs using specific primers for each gene. Results At least one AS event was found in 38.1% of the genes (3904 out of 10,245) in the protoscoleces during early strobilar development. The genes were associated primarily with cellular and metabolic processes and binding and catalytic activity. KEGG pathway analysis of DAS events revealed a number of genes belonging to different components of the spliceosome complex. These genes tended to belong to common SR proteins, U1-related factors, U2-related factors, complex A-specific factors and other splicing-related proteins. Conclusions The high number of AS events in the transcriptome regulatory mechanisms indicates the essential rapid molecular processes required by the parasite for adaptation in different environments. Graphical Abstract

Metacyclogenesis defects and gene expression hallmarks of histone deacetylase 4-deficient Trypanosoma cruzi cells

Trypanosoma cruzi—the causative agent of Chagas disease—like other kinetoplastids, relies mostly on post-transcriptional mechanisms for regulation of gene expression. However, trypanosomatids undergo drastic changes in nuclear architecture and chromatin structure along their complex life cycle which, combined with a remarkable set of reversible histone post-translational modifications, indicate that chromatin is also a target for control of gene expression and differentiation signals in these organisms. Chromatin-modifying enzymes have a direct impact on gene expression programs and DNA metabolism. In this work, we have investigated the function of T. cruzi histone deacetylase 4 (TcHDAC4). We show that, although TcHDAC4 is not essential for viability, metacyclic trypomastigote TcHDAC4 null mutants show a thin cell body and a round and less condensed nucleus located very close to the kinetoplast. Sixty-four acetylation sites were quantitatively evaluated, which revealed H2AT85ac, H4K10ac and H4K78ac as potential target sites of TcHDAC4. Gene expression analyses identified three chromosomes with overrepresented regions of differentially expressed genes in the TcHDAC4 knockout mutant compared with the wild type, showing clusters of either up or downregulated genes. The adjacent chromosomal location of some of these genes indicates that TcHDAC4 participates in gene expression regulation during T. cruzi differentiation.

Malaria Parasite Stress Tolerance Is Regulated by DNMT2-Mediated tRNA Cytosine Methylation

P. falciparum is the most virulent malaria parasite species, accounting for the majority of the disease mortality and morbidity. Understanding how this pathogen is able to adapt to different cellular and environmental stressors during its complex life cycle is crucial in order to develop new strategies to tackle the disease.

Cellular Proteo-Transcriptomic Changes in the Immediate Early-Phase of Lentiviral Transduction

Lentivirus-based vectors derived from human immunodeficiency viruses type 1 and 2 (HIV-1 and 2) are widely used tools in research and may also be utilized in clinical settings. Like their parental virions, they are known to depend on the cellular machinery for successful gene delivery and integration. While most of the studies on cellular proteomic and transcriptomic changes have focused on the late phase of the transduction, studies of those changes in early time-points, especially in the case of HIV-2 based vectors, are widely lacking. Using second generation HIV-1 and 2 vesicular stomatitis virus G protein (VSV-G) pseudotyped lentiviral vectors, we transduced HEK-293T human embryonic kidney cells and carried out transcriptomic profiling at 0 and 2 h time points, with accompanying proteomic analysis at 2 h following transduction. Significant variations were observed in gene expression profile between HIV-1 and HIV-2 transduced samples. Thrombospondin 1 (THBS1), collagens (COL1A2, COL3A1), and eukaryotic translation factors (EIF3CL) in addition to various genes coding for long non-coding RNA (lncRNA) were significantly upregulated 2 h after HIV-2 transduction compared to HIV-1. Label-free quantification mass spectrometry (MS) indicated that seven proteins involved in RNA binding, mRNA transport, and chaperoning were significantly downregulated. The identification of cellular protein targets of lentiviral vectors and their effect on the cellular transcriptome will undoubtedly shed more light on their complex life cycle and may be utilized against infection by their parental lentiviruses. Furthermore, characterizing the early phase of HIV-2 infection may aid in the understanding of its pathomechanism and long incubation period.

Inhibitors of the Plasmodium falciparum Hsp90 towards Selective Antimalarial Drug Design: The Past, Present and Future

Malaria is still one of the major killer parasitic diseases in tropical settings, posing a public health threat. The development of antimalarial drug resistance is reversing the gains made in attempts to control the disease. The parasite leads a complex life cycle that has adapted to outwit almost all known antimalarial drugs to date, including the first line of treatment, artesunate. There is a high unmet need to develop new strategies and identify novel therapeutics to reverse antimalarial drug resistance development. Among the strategies, here we focus and discuss the merits of the development of antimalarials targeting the Heat shock protein 90 (Hsp90) due to the central role it plays in protein quality control.