Trypanosoma cruzi Vps34 colocalizes with Beclin1 and plays a role in parasite invasion of the host cell by modulating the expression of a sub-group of trans-sialidases.

Trypanosoma cruzi, the etiological agent of Chagas' disease, can infect both phagocytic and non-phagocytic cells. T. cruzi gp82 and gp90 are cell surface proteins belonging to Group II trans-sialidases known to be involved in host cell binding and invasion. Phosphatidylinositol kinases (PIK) are lipid kinases that phosphorylate phospholipids in their substrates or in themselves, regulating important cellular functions such as metabolism, cell cycle and survival. Vps34, a class III PIK, regulates autophagy, trimeric G-protein signaling, and the mTOR (mammalian Target of Rapamycin) nutrient-sensing pathway. The mammalian autophagy gene Beclin1 interacts to Vps34 forming Beclin 1-Vps34 complexes involved in autophagy and protein sorting. In T. cruzi epimastigotes, (a non-infective replicative form), TcVps34 has been related to morphological and functional changes associated to vesicular trafficking, osmoregulation and receptor-mediated endocytosis. We aimed to characterize the role of TcVps34 during invasion of HeLa cells by metacyclic (MT) forms. MTs overexpressing TcVps34 showed lower invasion rates compared to controls, whilst exhibiting a significant decrease in gp82 expression in the parasite surface. In addition, we showed that T. cruzi Beclin (TcBeclin1) colocalizes with TcVps34 in epimastigotes, thus suggesting the formation of complexes that may play conserved cellular roles already described for other eukaryotes.

The Trypanosoma cruzi pleiotropic protein P21 orchestrates the intracellular retention and in-vivo parasitism control of virulent Y strain parasites.

P21 is a protein secreted by all forms of Trypanosoma cruzi (T. cruzi) with recognized biological activities determined in studies using the recombinant form of the protein. In our recent study, we found that the ablation of P21 gene decreased Y strain axenic epimastigotes multiplication and increased intracellular replication of amastigotes in HeLa cells infected with metacyclic trypomastigotes. In the present study, we investigated the effect of P21 in vitro using C2C12 cell lines infected with tissue culture-derived trypomastigotes (TCT) of wild-type and P21 knockout (TcP21-/-) Y strain, and in vivo using an experimental model of T. cruzi infection in BALB/c mice. Our in-vitro results showed a significant decrease in the host cell invasion rate by TcP21-/- parasites as measured by Giemsa staining and cell count in bright light microscope. Quantitative polymerase chain reaction (qPCR) analysis showed that TcP21-/- parasites multiplied intracellularly to a higher extent than the scrambled parasites at 72h post-infection. In addition, we observed a higher egress of TcP21-/- trypomastigotes from C2C12 cells at 144h and 168h post-infection. Mice infected with Y strain TcP21-/- trypomastigotes displayed higher systemic parasitemia, heart tissue parasite burden, and several histopathological alterations in heart tissues compared to control animals infected with scrambled parasites. Therewith, we propose that P21 is important in the host-pathogen interaction during invasion, cell multiplication, and egress, and may be part of the mechanism that controls parasitism and promotes chronic infection without patent systemic parasitemia.

Water deficit response in nodulated soybean roots: a comprehensive transcriptome and translatome network analysis.

BACKGROUND: Soybean establishes a mutualistic interaction with nitrogen-fixing rhizobacteria, acquiring most of its nitrogen requirements through symbiotic nitrogen fixation. This crop is susceptible to water deficit; evidence suggests that its nodulation status-whether it is nodulated or not-can influence how it responds to water deficit. The translational control step of gene expression has proven relevant in plants subjected to water deficit. RESULTS: Here, we analyzed soybean roots' differential responses to water deficit at transcriptional, translational, and mixed (transcriptional + translational) levels. Thus, the transcriptome and translatome of four combined-treated soybean roots were analyzed. We found hormone metabolism-related genes among the differentially expressed genes (DEGs) at the translatome level in nodulated and water-restricted plants. Also, weighted gene co-expression network analysis followed by differential expression analysis identified gene modules associated with nodulation and water deficit conditions. Protein-protein interaction network analysis was performed for subsets of mixed DEGs of the modules associated with the plant responses to nodulation, water deficit, or their combination. CONCLUSIONS: Our research reveals that the stand-out processes and pathways in the before-mentioned plant responses partially differ; terms related to glutathione metabolism and hormone signal transduction (2 C protein phosphatases) were associated with the response to water deficit, terms related to transmembrane transport, response to abscisic acid, pigment metabolic process were associated with the response to nodulation plus water deficit. Still, two processes were common: galactose metabolism and branched-chain amino acid catabolism. A comprehensive analysis of these processes could lead to identifying new sources of tolerance to drought in soybean.

Adaptive Mentoring Networks and Compassionate Care: A Qualitative Exploration of Mentorship for Chronic Pain, Substance Use Disorders and Mental Health.

This study undertook an exploration of how Adaptive Mentoring Networks focusing on chronic pain, substance use disorders and mental health were supporting primary care providers to engage in compassionate care. The study utilised the Cole-King & Gilbert Compassionate Care Framework to guide qualitative semi-structured interviews of participants in two Adaptive Mentoring Networks in Ontario, Canada. Fourteen physician participants were interviewed including five mentors (psychiatrists) and nine mentees (family physicians) in the Networks. The Cole-King & Gilbert Framework helped provide specific insights on how these mentoring networks were affecting the attributes of compassion such as motivation, distress-tolerance, non-judgement, empathy, sympathy, and sensitivity. The findings of this study focused on the role of compassionate provider communities and the development of skills and attitudes related to compassion that were both being supported in these networks. Adaptive Mentoring Networks can support primary care providers to offer compassionate care to patients with chronic pain, substance use disorders, and mental health challenges. This study also highlights how these networks had an impact on provider resiliency, and compassion fatigue. There is promising evidence these networks can support the "quadruple aim" for healthcare systems (improve patient and provider experience, health of populations and value for money) and play a role in addressing the healthcare provider burnout and associated health workforce crisis.

The Risk Factors of Dewclaw Dermatitis in Beef Cattle in the Amazon Biome.

Bovine Dewclaw Dermatitis (BDCD) is a hoof disease characterized by inflammation of the second and fifth accessory digits and the skin in this region. This pathology is poorly described in the literature; however, it has recently been observed in beef cattle in the Amazon Biome, Brazil. The objective of this study was to perform a clinical diagnosis and identify the risk factors associated with BDCD onset in cattle in the studied biome. Samples were collected from eight farms with extensive breeding systems located in Xinguara, Rondon do Pará, Curionópolis, and Ipixuna do Pará in the state of Pará, Brazil. A total of 706 Nellore and Nellore crossbred with taurine bovine of both sexes were evaluated, with males aged between 2 and 4 years and a mean weight of 650 kg, and females aged between 2 and 11 years and a mean weight of 400 kg. Distal extremities were inspected during cattle management, and in cases of dewclaw lesions, a specific examination was carried out after proper restraint. Cattle were diagnosed with BDCD on all farms analyzed. Of the 706 cattle inspected, 49 (6.94%) showed BDCD, of which 19 (38.77%) were Nellore and 30 (61.22%) were crossbred. This was the first study to determine BDCD's occurrence in extensive farming systems in the Amazon region, also showing that pastures with large amounts of stumps and stones, the physical structure of pens, and trauma and injury incidence during animal management are the most important predisposing factors for the onset of BDCD.

Allergic Dermatitis in Pêga Breed Donkeys (Equus asinus) Caused by Culicoides Bites in the Amazon Biome, Pará, Brazil.

An allergy to bites from Culicoides (Diptera: Ceratopogonidae) occurs because of a hypersensitivity reaction caused by the inoculation of insect salivary antigens during the bite, resulting in immune-mediated dermatitis. To the best of our knowledge, no previous studies have focused on allergic dermatitis in donkeys in Brazil. Therefore, this study aimed to describe the epidemiological, clinicopathological, and therapeutic aspects of allergic dermatitis in donkeys and to identify the insects involved in its epidemiology. This study reported the occurrence of dermatitis in 17 animals. The clinical signs were restlessness and severe itching. Skin lesions were found on the head, depigmented areas of the muzzle and cheeks, flanks, pelvic and thoracic limbs, and the scrotal sac. The lesions were characterized by areas of alopecia with crusts accompanied by serosanguineous exudates. Histologically, the lesions were characterized as moderate superficial dermatitis with irregular epidermal acanthosis and pronounced diffuse orthokeratotic hyperkeratosis. In total, 378 Culicoides specimens were collected, with Culicoides ocumarensis Ortiz being the most abundant species. The combined application of copaiba oil and a multivitamin emulsion exhibited potential for topical treatment of allergic dermatitis caused by insect bites in donkeys. Our study revealed an association between allergic dermatitis in donkeys and Culicoides.

Differential effects of coverslip-induced hypoxia and cobalt chloride mimetic hypoxia on cellular stress, metabolism, and nuclear structure.

Hypoxia has profound effects on cell physiology, both in normal or pathological settings like cancer. In this study, we asked whether a variant of coverslip-induced hypoxia that recapitulates the conditions found in the tumor microenvironment would elicit similar cellular responses compared to the well established model of cobalt chloride-induced hypoxia. Comparable levels of nuclear HIF-1α were observed after 24 h of coverslip-induced hypoxia or cobalt chloride treatment in CAL-27 oral squamous carcinoma cells. However, cellular stress levels assessed by reactive oxygen species production and lipid droplet accumulation were markedly increased in coverslip-induced hypoxia compared to cobalt chloride treatment. Conversely, mitochondrial ATP production sharply decreased after coverslip-induced hypoxia but was preserved in the presence of cobalt chloride. Coverslip-induced hypoxia also had profound effects in nuclear organization, assessed by changes in nuclear dry mass distribution, whereas these effects were much less marked after cobalt chloride treatment. Taken together, our results show that coverslip-induced hypoxia effects on cell physiology and structure are more pronounced than mimetic hypoxia induced by cobalt chloride treatment. Considering also the simplicity of coverslip-induced hypoxia, our results therefore underscore the usefulness of this method to recapitulate in vitro the effects of hypoxic microenvironments encountered by cells in vivo.

Transcriptomic analysis of N-terminal mutated Trypanosoma cruzi UBP1 knockdown underlines the importance of this RNA-binding protein in parasite development.

BACKGROUND: During its life cycle, the human pathogen Trypanosoma cruzi must quickly adapt to different environments, in which the variation in the gene expression of the regulatory U-rich RNA-binding protein 1 (TcUBP1) plays a crucial role. We have previously demonstrated that the overexpression of TcUBP1 in insect-dwelling epimastigotes orchestrates an RNA regulon to promote differentiation to infective forms. METHODS: In an attempt to generate TcUBP1 knockout parasites by using CRISPR-Cas9 technology, in the present study, we obtained a variant transcript that encodes a protein with 95% overall identity and a modified N-terminal sequence. The expression of this mutant protein, named TcUBP1mut, was notably reduced compared to that of the endogenous form found in normal cells. TcUBP1mut-knockdown epimastigotes exhibited normal growth and differentiation into infective metacyclic trypomastigotes and were capable of infecting mammalian cells. RESULTS: We analyzed the RNA-Seq expression profiles of these parasites and identified 276 up- and 426 downregulated genes with respect to the wildtype control sample. RNA-Seq comparison across distinct developmental stages revealed that the transcriptomic profile of these TcUBP1mut-knockdown epimastigotes significantly differs not only from that of epimastigotes in the stationary phase but also from the gene expression landscape characteristic of infective forms. This is both contrary to and consistent with the results of our recent study involving TcUBP1-overexpressing cells. CONCLUSION: Together, our findings demonstrate that the genes exhibiting opposite changes under overexpression and knockdown conditions unveil key mRNA targets regulated by TcUBP1. These mostly encompass transcripts that encode for trypomastigote-specific surface glycoproteins and ribosomal proteins, supporting a role for TcUBP1 in determining the molecular characteristics of the infective stage.

Nurturing an organizational context that supports team-based primary mental health care: A grounded theory study.

BACKGROUND: The expansion of the Patient-Centred Medical Home model presents a valuable opportunity to enhance the integration of team-based mental health services in primary care settings, thereby meeting the growing demand for such services. Understanding the organizational context of a Patient-Centred Medical Home is crucial for identifying the facilitators and barriers to integrating mental health care within primary care. The main objective of this paper is to present the findings related to the following research question: "What organizational features shape Family Health Teams' capacity to provide mental health services for depression and anxiety across Ontario, Canada?" METHODS: Adopting a constructivist grounded theory approach, we conducted interviews with various mental health care providers, and administrators within Ontario's Family Health Teams, in addition to engaging provincial policy informants and community stakeholders. Data analysis involved a team-based approach, including code comparison and labelling, with a dedicated data analysis subcommittee convening monthly to explore coded concepts influencing contextual factors. RESULTS: From the 96 interviews conducted, involving 82 participants, key insights emerged on the organizational contextual features considered vital in facilitating team-based mental health care in primary care settings. Five prominent themes were identified: i) mental health explicit in the organizational vision, ii) leadership driving mental health care, iii) developing a mature and stable team, iv) adequate physical space that facilitates team interaction, and v) electronic medical records to facilitate team communication. CONCLUSIONS: This study underscores the often-neglected organizational elements that influence primary care teams' capacity to deliver quality mental health care services. It highlights the significance of strong leadership complemented by effective communication and collaboration within teams to enhance their ability to provide mental health care. Strengthening relationships within primary care teams lies at the core of effective healthcare delivery and should be leveraged to improve the integration of mental health care.

A Single-Port, Multiple-Access, Custom-Made Device Used in Laparoscopically Assisted Cryptorchidectomy in Standing Horses-A Preliminary Study.

This study evaluates a new multiport device with single access to the abdominal cavity produced with routine hospital supplies that could be applied to laparoscopically assisted cryptorchidectomy in standing horses. Initially, the new device was evaluated on five cadavers of bovine fetuses (n = 5), placed assisted in a minilaparotomy performed in the flank region. Subsequently, the device was evaluated in four cryptorchid horses treated during the hospital routine. During the evaluation of the new device, the possibilities of exploring the abdominal cavity, inspection, and intra-abdominal manipulation with two Babcock forceps were verified. The possibilities were described, and surgical time data were recorded and analyzed using descriptive statistics. In the cadavers, a wide exploration of the abdominal cavity was possible, with a laparoscopic inspection through the right paralumbar fossa and manipulation of intra-abdominal structures with Babcock forceps inserted by the new device. In cryptorchid horses, laparoscopically assisted cryptorchidectomy with a new device was feasible in two patients, and in the others, it allowed the diagnosis of adhesions and ectopic locations in the inguinal region of testicles retained in the cavity. Therefore, the new device was efficient in exploring the inguinal region of cryptorchid horses in the standing position. The present study is preliminary and can support future studies that aim to improve the developed prototype.

Uncovering a multitude of stage-specific splice variants and putative protein isoforms generated along mouse spermatogenesis.

BACKGROUND: Mammalian testis is a highly complex and heterogeneous tissue. This complexity, which mostly derives from spermatogenic cells, is reflected at the transcriptional level, with the largest number of tissue-specific genes and long noncoding RNAs (lncRNAs) compared to other tissues, and one of the highest rates of alternative splicing. Although it is known that adequate alternative-splicing patterns and stage-specific isoforms are critical for successful spermatogenesis, so far only a very limited number of reports have addressed a detailed study of alternative splicing and isoforms along the different spermatogenic stages. RESULTS: In the present work, using highly purified stage-specific testicular cell populations, we detected 33,002 transcripts expressed throughout mouse spermatogenesis not annotated so far. These include both splice variants of already annotated genes, and of hitherto unannotated genes. Using conservative criteria, we uncovered 13,471 spermatogenic lncRNAs, which reflects the still incomplete annotation of lncRNAs. A distinctive feature of lncRNAs was their lower number of splice variants compared to protein-coding ones, adding to the conclusion that lncRNAs are, in general, less complex than mRNAs. Besides, we identified 2,794 unannotated transcripts with high coding potential (including some arising from yet unannotated genes), many of which encode unnoticed putative testis-specific proteins. Some of the most interesting coding splice variants were chosen, and validated through RT-PCR. Remarkably, the largest number of stage-specific unannotated transcripts are expressed during early meiotic prophase stages, whose study has been scarcely addressed in former transcriptomic analyses. CONCLUSIONS: We detected a high number of yet unannotated genes and alternatively spliced transcripts along mouse spermatogenesis, hence showing that the transcriptomic diversity of the testis is considerably higher than previously reported. This is especially prominent for specific, underrepresented stages such as those of early meiotic prophase, and its unveiling may constitute a step towards the understanding of their key events.

RNA-seq data exploration after trypanosome RNA-binding protein UBP1 expression is altered by CRISPR-Cas9 gene editing and overexpression.

Previous studies have shown that overexpression of the Trypanosoma cruzi U-rich RNA-binding protein 1 (TcUBP1) in insect-dwelling epimastigotes results in a gene expression pattern resembling that of the infective form of the pathogen. Here, we used CRISPR-Cas9-induced edition of TcUBP1 and full-length protein overexpression in epimastigote cells to monitor transcriptomic changes during the epimastigote-to-metacyclic trypomastigote stage transition of T. cruzi. This dataset includes the bioinformatics analysis of three different RNA-seq samples, each with three biological replicates, showing differential mRNA abundances. The current transcriptome report has the potential to shed light on the quantitative variances in the expression of significant up- or down-regulated mRNAs as a consequence of the levels of the UBP1 protein. Raw data files were deposited at the NCBI Sequence Read Archive - SRA at http://ncbi.nlm.nih.gov/Traces/sra/sra.cgi with accession numbers PRJNA907231 and PRJNA949967.

Genomic characterization of Moraxella bovis and Moraxella bovoculi Uruguayan strains isolated from calves with infectious bovine keratoconjunctivitis.

Infectious bovine keratoconjunctivitis (IBK) is an ocular disease that affects bovines and has significant economic and health effects worldwide. Gram negative bacteria Moraxella bovis and Moraxella bovoculi are its main etiological agents. Antimicrobial therapy against IBK is often difficult in beef and dairy herds and, although vaccines are commercially available, their efficacy is variable and dependent on local strains. The aim of this study was to analyze for the first time the genomes of Uruguayan clinical isolates of M. bovis and M. bovoculi. The genomes were de novo assembled and annotated; the genetic basis of fimbrial synthesis was analyzed and virulence factors were identified. A 94% coverage in the reference genomes of both species, and more than 80% similarity to the reference genomes were observed. The mechanism of fimbrial phase variation in M. bovis was detected, and the tfpQ orientation of these genes confirmed, in an inversion region of approximately 2.18kb. No phase variation was determined in the fimbrial gene of M. bovoculi. When virulence factors were compared between strains, it was observed that fimbrial genes have 36.2% sequence similarity. In contrast, the TonB-dependent lactoferrin/transferrin receptor exhibited the highest percentage of amino acid similarity (97.7%) between strains, followed by cytotoxins MbxA/MbvA and the ferric uptake regulator. The role of these virulence factors in the pathogenesis of IBK and their potential as vaccine components should be explored.

Extracutaneous Melanotic Melanoma with Nervous System Involvement in a Buffalo (Bubalus bubalis).

Melanomas are tumors arising from externally uncontrolled melanocytes that produce varying amounts of melanin. In this study, we report a case of melanoma with neurological impairment without evidence of cutaneous neoplastic lesions in an adult buffalo in the state of Pará, Brazil. Clinically, the buffalo exhibited apathy, decreased mandibular tone, and occasionally an open mouth with motor incoordination, and eventually succumbed to the condition. Necropsy revealed multifocal tumor masses in the brain, pituitary gland, trigeminal ganglion, and spinal cord. The neoplastic cells showed strong positive signals for vimentin, Melan-A, PNL-2, and SOX10. The diagnosis was made via necropsy, histopathology, and positive immunostaining for Melan-A and PNL-2, which are specific markers for melanocyte identification.

Contributions of viral oncogenes of HPV-18 and hypoxia to oxidative stress and genetic damage in human keratinocytes.

Infection with high-risk human papillomaviruses like HPV-16 and HPV-18 is highly associated with the development of cervical and other cancers. Malignant transformation requires viral oncoproteins E5, E6 and E7, which promote cell proliferation and increase DNA damage. Oxidative stress and hypoxia are also key factors in cervical malignant transformation. Increased levels of reactive species of oxygen (ROS) and nitrogen (RNS) are found in the hypoxic tumor microenvironment, promoting genetic instability and invasiveness. In this work, we studied the combined effect of E5, E6 and E7 and hypoxia in increasing oxidative stress and promoting DNA damage and nuclear architecture alterations. HaCaT cells containing HPV-18 viral oncogenes (HaCaT E5/E6/E7-18) showed higher ROS levels in normoxia and higher levels of RNS in hypoxia compared to HaCaT parental cells, as well as higher genetic damage in hypoxia as measured by γH2AX and comet assays. In hypoxia, HaCaT E5/E6/E7-18 increased its nuclear dry mass and both cell types displayed marked heterogeneity in nuclear dry mass distribution and increased nuclear foci. Our results show contributions of both viral oncogenes and hypoxia to oxidative stress, DNA damage and altered nuclear architecture, exemplifying how an altered microenvironment combines with oncogenic transformation to promote tumor progression.

Translational control by Trypanosoma brucei DRBD18 contributes to the maintenance of the procyclic state.

Trypanosoma brucei occupies distinct niches throughout its life cycle, within both the mammalian and tsetse fly hosts. The immunological and biochemical complexity and variability of each of these environments require a reshaping of the protein landscape of the parasite both to evade surveillance and face changing metabolic demands. In kinetoplastid protozoa, including T. brucei, posttranscriptional control mechanisms are the primary means of gene regulation, and these are often mediated by RNA-binding proteins. DRBD18 is a T. brucei RNA-binding protein that reportedly interacts with ribosomal proteins and translation factors. Here, we tested a role for DRBD18 in translational control. We validate the DRBD18 interaction with translating ribosomes and the translation initiation factor, eIF3a. We further show that DRBD18 depletion by RNA interference leads to altered polysomal profiles with a specific depletion of heavy polysomes. Ribosome profiling analysis reveals that 101 transcripts change in translational efficiency (TE) upon DRBD18 depletion: 41 exhibit decreased TE and 60 exhibit increased TE. A further 66 transcripts are buffered, that is, changes in transcript abundance are compensated by changes in TE such that the total translational output is expected not to change. In DRBD18-depleted cells, a set of transcripts that codes for procyclic form-specific proteins is translationally repressed while, conversely, transcripts that code for bloodstream form- and metacyclic form-specific proteins are translationally enhanced. RNA immunoprecipitation/qRT-PCR indicates that DRBD18 associates with members of both repressed and enhanced cohorts. These data suggest that DRBD18 contributes to the maintenance of the procyclic state through both positive and negative translational control of specific mRNAs.

Correction: Sainz et al. Analysis of Thioredoxins and Glutaredoxins in Soybean: Evidence of Translational Regulation under Water Restriction. Antioxidants 2022, 11, 1622.

In the original publication [...].

A methodological proposal to analyze urban sprawl, negative environmental impacts, and land degradation in the case of João Pessoa City (Brazil) between 1991 and 2018.

Urbanization and changes in urban spaces have caused severe environmental and social problems in large Brazilian cities. As such, this study presents a methodological proposal to analyze urban sprawl, negative environmental impacts, and land degradation. The methodology employed involves a combination of remote sensing data, environmental modeling techniques, and mixed-method analyses of environmental impacts from 1991 to 2018. Analyzed variables included vegetation, surface temperature, water quality, and soil degradation within the study area. These variables were assessed based on an interaction matrix used to evaluate environmental impacts (low, medium, or high impacts). The obtained results show conflicts of land use and land cover (LULC), a lack of urban sanitation infrastructure, and an absence of environmental monitoring and inspection. A reduction of 24 km2 of arboreal vegetation was observed from 1991 to 2018. High values of fecal coliforms were found in March across nearly all analyzed points, indicating a seasonal discharge of effluents. The interaction matrix presented various negative environmental impacts, including increased land surface temperature, soil degradation, inappropriate solid waste disposal, devastation of remaining vegetation, water pollution by domestic effluents, and the incidence of erosive processes. Ultimately, the impact quantification determined that the study area has a medium degree of significance in terms of environmental impacts. Thus, refining this quantification method will contribute to future research by making the analysis processes more objective and efficient.

Omics data integration facilitates target selection for new antiparasitic drugs against TriTryp infections.

Introduction: Trypanosoma cruzi, Trypanosoma brucei, and Leishmania spp., commonly referred to as TriTryps, are a group of protozoan parasites that cause important human diseases affecting millions of people belonging to the most vulnerable populations worldwide. Current treatments have limited efficiencies and can cause serious side effects, so there is an urgent need to develop new control strategies. Presently, the identification and prioritization of appropriate targets can be aided by integrative genomic and computational approaches. Methods: In this work, we conducted a genome-wide multidimensional data integration strategy to prioritize drug targets. We included genomic, transcriptomic, metabolic, and protein structural data sources, to delineate candidate proteins with relevant features for target selection in drug development. Results and Discussion: Our final ranked list includes proteins shared by TriTryps and covers a range of biological functions including essential proteins for parasite survival or growth, oxidative stress-related enzymes, virulence factors, and proteins that are exclusive to these parasites. Our strategy found previously described candidates, which validates our approach as well as new proteins that can be attractive targets to consider during the initial steps of drug discovery.