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Sci Rep ; 9(1): 19841, 2019 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-31882833


The fate of Leishmania infection can be strongly influenced by the host genetic background. In this work, we describe gene expression modulation of the immune system based on dual global transcriptome profiles of bone marrow-derived macrophages (BMDMs) from BALB/c and C57BL/6 mice infected with Leishmania amazonensis. A total of 12,641 host transcripts were identified according to the alignment to the Mus musculus genome. Differentially expressed genes (DEGs) profiling revealed a differential modulation of the basal genetic background between the two hosts independent of L. amazonensis infection. In addition, in response to early L. amazonensis infection, 10 genes were modulated in infected BALB/c vs. non-infected BALB/c macrophages; and 127 genes were modulated in infected C57BL/6 vs. non-infected C57BL/6 macrophages. These modulated genes appeared to be related to the main immune response processes, such as recognition, antigen presentation, costimulation and proliferation. The distinct gene expression was correlated with the susceptibility and resistance to infection of each host. Furthermore, upon comparing the DEGs in BMDMs vs. peritoneal macrophages, we observed no differences in the gene expression patterns of Jun, Fcgr1 and Il1b, suggesting a similar activation trends of transcription factor binding, recognition and phagocytosis, as well as the proinflammatory cytokine production in response to early L. amazonensis infection. Analysis of the DEG profile of the parasite revealed only one DEG among the 8,282 transcripts, indicating that parasite gene expression in early infection does not depend on the host genetic background.

Tidsskr Nor Laegeforen ; 139(13)2019 Sep 24.
Artigo em Inglês, Norueguês | MEDLINE | ID: mdl-31556531


BACKGROUND: Febrile illness is a common clinical problem and frequently caused by bacterial and viral infections. When blood cultures are negative and symptoms persist despite empirical antibiotic treatment, clinicians must consider other differential diagnoses including malignancy, rheumatologic disease and parasitic infections. CASE PRESENTATION: A Norwegian male in his eighties experienced febrile illness during a stay in Southern Spain. Upon return to Norway, he was hospitalized with fever, weight-loss, enlarged spleen, pancytopenia and hypergammaglobulinemia. After failing to respond to broad-spectrum antibiotics and antifungals, he was diagnosed with visceral leishmaniasis and Leishmania infantum was confirmed by PCR and sequencing of spleen biopsy and blood. INTERPRETATION: With increasing migration and tourism, doctors in non-endemic countries should be familiar with visceral leishmaniasis.

Leishmaniose Visceral/diagnóstico , Idoso de 80 Anos ou mais , Anfotericina B/administração & dosagem , Anfotericina B/uso terapêutico , Antiprotozoários/administração & dosagem , Antiprotozoários/uso terapêutico , Artrite/parasitologia , Febre/parasitologia , Humanos , Leishmania infantum/crescimento & desenvolvimento , Leishmania infantum/isolamento & purificação , Leishmaniose Visceral/complicações , Leishmaniose Visceral/tratamento farmacológico , Masculino , Pancitopenia/parasitologia , Espanha , Esplenomegalia/diagnóstico por imagem , Esplenomegalia/parasitologia , Tomografia Computadorizada por Raios X , Doença Relacionada a Viagens
Tidsskr Nor Laegeforen ; 139(3)2019 02 12.
Artigo em Inglês, Norueguês | MEDLINE | ID: mdl-30754951


BAKGRUNN: I 2002 ble Forskerlinjen opprettet for tidlig å rekruttere medisinstudenter til forskning. Vi ønsket å kartlegge hvor mange tidligere forskerlinjestudenter fra Universitetet i Bergen som fortsatte å forske og identifisere faktorer som var assosiert med videre forskning. MATERIALE OG METODE: Alle studenter innrullert i forskerlinjeprogrammet ved Universitetet i Bergen siden oppstart i 2002 som var uteksaminert fra medisinstudiet innen juni 2017 ble kontaktet per e-post med en elektronisk spørreundersøkelse. Vi undersøkte om deltagerne holdt på med eller hadde gjennomført doktorgrad, antall publiserte artikler, tid siden siste publisering, akademisk undervisning og veiledning samt nåværende stilling på universitet eller høyskole. RESULTATER: Totalt 102 av 148 (69 %) besvarte spørreundersøkelsen. Av disse hadde 68 % gått videre med doktorgrad, 38 % var involvert i akademisk undervisning eller veiledning og 29 % var ansatt i en akademisk stilling. Samlet hadde deltagerne i median publisert fire artikler. Kvinner hadde større sannsynlighet for å gå videre med doktorgrad enn menn. Det samme hadde de som publiserte minst én artikkel før fullført medisinstudium, og de som ikke hadde mottatt regelmessig veiledning som forskerlinjestudent. Det var ingen sammenheng mellom det å fullføre Forskerlinjen og det å gå videre med doktorgrad. FORTOLKNING: Mange medisinstudenter som har gått Forskerlinjen ved Universitetet i Bergen fortsetter med forskning etter fullført studium. Dette gjelder også de som ikke fullfører linjen.

Pesquisa Biomédica/educação , Educação Médica , Pesquisadores/estatística & dados numéricos , Dissertações Acadêmicas como Assunto , Adulto , Escolha da Profissão , Educação de Pós-Graduação/estatística & dados numéricos , Docentes de Medicina/estatística & dados numéricos , Feminino , Humanos , Masculino , Noruega , Publicações/estatística & dados numéricos , Distribuição por Sexo , Estudantes de Medicina , Inquéritos e Questionários , Ensino/estatística & dados numéricos
Parasit Vectors ; 11(1): 421, 2018 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-30012182


BACKGROUND: The leishmaniases comprise a spectrum of clinical manifestations caused by different species of Leishmania. Identification of species is important for diagnosis, treatment and follow-up management. However, there is no gold standard for species identification. High resolution melting analysis (HRM) offers a possibility to differentiate Leishmania species without the need for processing of the PCR-product. The amino acid permease 3 (aap3) gene is an exclusive target for trypanosomatids and is conserved among Leishmania spp., thus it can be a valuable target for an HRM assay for diagnosis of the leishmaniases. RESULTS: The HRM dissociation profiles of three amplicons targeting the aap3-coding region allowed the discrimination of L. (Leishmania) donovani, L. (L.) infantum, L. (L.) major, L. (L.) tropica, L. (L.) mexicana, L. (L.) amazonensis, L. (Viannia) braziliensis, L. (V.) guyanensis, L. (V.) lainsoni, L. (V.) naiffi and L. (V.) shawi using DNA from promastigote cultures. The protocol was validated with DNA samples from clinical infection in humans and a cat, naturally infected sand flies, and experimentally infected mice. CONCLUSIONS: HRM analysis using the aap3 coding sequence as target is a relatively cheap, fast and robust strategy to detect and discriminate Leishmania species from all the endemic regions worldwide. The target and method proved to be useful in clinical, field and experimental samples, thus it could be used as a tool in diagnosis as well as ecological and epidemiological studies.

Sistemas de Transporte de Aminoácidos/genética , Leishmania/classificação , Leishmania/enzimologia , Leishmaniose/diagnóstico , Animais , Sequência de Bases , DNA de Protozoário/genética , Leishmaniose/parasitologia , Camundongos , Desnaturação de Ácido Nucleico , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
PLoS Negl Trop Dis ; 11(10): e0006026, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29077741


BACKGROUND: Leishmania is a protozoan parasite that alternates its life cycle between the sand-fly vector and the mammalian host. This alternation involves environmental changes and leads the parasite to dynamic modifications in morphology, metabolism, cellular signaling and regulation of gene expression to allow for a rapid adaptation to new conditions. The L-arginine pathway in L. amazonensis is important during the parasite life cycle and interferes in the establishment and maintenance of the infection in mammalian macrophages. Host arginase is an immune-regulatory enzyme that can reduce the production of nitric oxide by activated macrophages, directing the availability of L-arginine to the polyamine pathway, resulting in parasite replication. In this work, we performed transcriptional profiling to identify differentially expressed genes in L. amazonensis wild-type (La-WT) versus L. amazonensis arginase knockout (La-arg-) promastigotes and axenic amastigotes. METHODOLOGY/PRINCIPAL FINDINGS: A total of 8253 transcripts were identified in La-WT and La-arg- promastigotes and axenic amastigotes, about 60% of them codifying hypothetical proteins and 443 novel transcripts, which did not match any previously annotated genes. Our RNA-seq data revealed that 85% of genes were constitutively expressed. The comparison of transcriptome and metabolome data showed lower levels of arginase and higher levels of glutamate-5-kinase in La-WT axenic amastigotes compared to promastigotes. The absence of arginase activity in promastigotes increased the levels of pyrroline 5-carboxylate reductase, but decreased the levels of arginosuccinate synthase, pyrroline 5-carboxylate dehydrogenase, acetylornithine deacetylase and spermidine synthase transcripts levels. These observations can explain previous metabolomic data pointing to the increase of L-arginine, citrulline and L-glutamate and reduction of aspartate, proline, ornithine and putrescine. Altogether, these results indicate that arginase activity is important in Leishmania gene expression modulation during differentiation and adaptation to environmental changes. Here, we confirmed this hypothesis with the identification of differential gene expression of the enzymes involved in biosynthesis of amino acids, arginine and proline metabolism and arginine biosynthesis. CONCLUSIONS/SIGNIFICANCE: All data provided information about the transcriptomic profiling and the expression levels of La-WT and La-arg- promastigotes and axenic amastigotes. These findings revealed the importance of arginase in parasite survival and differentiation, and indicated the existence of a coordinated response in the absence of arginase activity related to arginine and polyamine pathways.

Arginase/metabolismo , Regulação da Expressão Gênica , Leishmania mexicana/genética , Análise de Sequência de RNA , Arginase/genética , Arginina/biossíntese , Arginina/metabolismo , Expressão Gênica , Perfilação da Expressão Gênica/métodos , Técnicas de Inativação de Genes , Leishmania mexicana/enzimologia , Leishmania mexicana/crescimento & desenvolvimento , Leishmania mexicana/metabolismo , Macrófagos/parasitologia , Óxido Nítrico/metabolismo , Poliaminas/metabolismo
Acta Trop ; 137: 99-104, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24859532


Leishmaniasis is one of the world's most neglected infectious diseases, affecting around 12 million people and more than 350 million at risk of infection. The clinical picture varies from self-healing cutaneous lesions to severe visceral infections, but still no commercial vaccines for humans are available and the currently used drugs have unpleasant side effects. Here we report a real-time PCR assay targeting the arginine permease gene AAP3 that can be applied for all the nine different species of the Leishmania genus tested; 4 Old World species and 5 New World species, from both L. (Leishmania) and L. (Viannia) subgenera. No cross-reaction was seen with Trypanosoma cruzi, Trypanosoma brucei, human or mouse genomic DNA. The assay has a high sensitivity, with a limit of detection of 10fg DNA for L. (L.) major and L. (L.) donovani, and 100fg DNA for L. (V.) braziliensis, and can be used for both qualitative and quantitative purposes. This AAP3-Assay, run in duplex with a host specific gene-assay, was also successfully used for quantification of parasite load of footpads from L. (L.) major-infected mice. It can therefore be a valuable tool in applications like monitoring effects of drugs, the selection of vaccine candidates and in screening patients, including asymptomatic carriers.

Sistemas de Transporte de Aminoácidos Básicos/genética , Leishmania/classificação , Leishmania/isolamento & purificação , Leishmaniose/parasitologia , Carga Parasitária/métodos , Proteínas de Protozoários/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , Animais , Modelos Animais de Doenças , Feminino , Camundongos Endogâmicos BALB C , Sensibilidade e Especificidade