The CCAAT-Binding Complex Controls Respiratory Gene Expression and Iron Homeostasis in Candida Glabrata

International audienceThe CCAAT-binding complex (CBC) is a heterotrimeric transcription factor which is widely conserved in eukaryotes. In the model yeast S. cerevisiae, CBC positively controls the expression of respiratory pathway genes. This role involves interactions with the regulatory subunit Hap4. In many pathogenic fungi, CBC interacts with the HapX regulatory subunit to control iron homeostasis. HapX is a bZIP protein which only shares with Hap4 the Hap4Like domain (Hap4L) required for its interaction with CBC. Here, we show that CBC has a dual role in the pathogenic yeast C. glabrata. It is required, along with Hap4, for the constitutive expression of respiratory genes and it is also essential for the iron stress response, which is mediated by the Yap5 bZIP transcription factor. Interestingly, Yap5 contains a vestigial Hap4L domain. The mutagenesis of this domain severely reduced Yap5 binding to its targets and compromised its interaction with Hap5. Hence, Yap5, like HapX in other species, acts as a CBC regulatory subunit in the regulation of iron stress response. This work reveals new aspects of iron homeostasis in C. glabrata and of the evolution of the role of CBC and Hap4L-bZIP proteins in this process

Scavenger birds exploiting rubbish dumps: Pathogens at the gates

Different bacteria are present in rubbish dumps used as food resources by various bird species. Birds may be good indicators of the presence of zoonotic diseases in these sites since they can be infected with zoonotic pathogens by foraging on organic waste, and can also act as carriers. We studied if foraging in rubbish dumps increases the occurrence of Salmonella spp. and Chlamydia psittaci in American black vultures (Coragyps atratus, hereafter black vultures) from northwest Patagonia. We compared these pathogens isolated from or detected in cloacae and oropharynx swabs in two different groups of black vultures: individuals trapped in (a) the Patagonian wild steppe and (b) in a rubbish dump. We found that black vultures are colonized by Salmonella spp. (particularly Salmonella enterica serotypes Typhi, Paratyphi A, Salmonella enterica subsp. arizonae) and Chlamydia psittaci. Interestingly, there were differences in the prevalence of Salmonella spp., especially Salmonella Typhi, between individuals foraging in the rubbish dump and the steppe, but not in the prevalence of Chlamydia psittaci. The pathogens isolated from black vultures may impact their health status but could also have health impacts in other bird species and even humans. In fact, Salmonella Typhi can cause severe disease in humans leading to death. Our results are globally relevant given that bacterial infections from rubbish dumps may affect different species exploiting these sites around the world. There is a need to better control pathogens in rubbish dumps to avoid the risk of infecting wildlife, which could act as potential dispersers and reservoirs of these pathogens.We thank Agencia Nacional de Promoción Científica y Tecnológica (ANPCYT–FONCYT, PICT (BID) 0725-2014, Argentina) and Universidad Nacional del Comahue project 04/B227 for financial support

Brucella canis Group 2 isolated in Argentina = Brucella canis Grupo 2 aislado en Argentina

The aim of this study was to estimate the diversity and prevalence of both groups of Brucella canis 1 and 2 with and without deletion respectively in different areas of Argentina. A total of 104 bacterial cultures were typed as B. canis strains using the classical biotyping method. Two PCR assays were performed to confirm that all isolates were B. canis and not Brucella suis. The differentiation between groups 1 and 2 was achieved using another PCR assay and the diversity of B. canis isolates was assessed with four MLVA_16 markers. All strains belonged to Group 2. Bruce 09 marker (MLVA_16 assay) showed the greatest diversity. Only Group 2 of B. canis was identified among the strains evaluated. The markers chosen from the MLVA_16 allowed us to detect genetic diversity among the strains of B. canis studied.El objetivo de este trabajo fue estimar la diversidad y la prevalencia de ambos grupos de Brucella canis 1 y 2 (con y sin deleción, respectivamente) en diferentes áreas de Argentina. Un total de 104 cultivos bacterianos se tipificaron como cepas de B. canis usando biotipado clásico. Se realizaron dos ensayos de PCR para confirmar que todos los aislamientos eran B. canis y no Brucella suis. La diferenciación entre los grupos 1 y 2 se logró con otro ensayo de PCR, y la diversidad entre las cepas de B. canis se obtuvo mediante el empleo de cuatro marcadores del ensayo de MLVA_16. Todas las cepas pertenecieron al grupo 2. El marcador Bruce 09 (ensayo MVLA-16) mostró la mayor diversidad. Sólo se halló el Grupo 2 de B. canis entre las cepas estudiadas. Los marcadores del MLVA_16 permitieron detectar la presencia de diversidad genética entre las cepas de B. canis analizadas.Instituto de BiotecnologíaFil: Boeri, Eduardo Jorge. Instituto de Zoonosis Luis Pasteur; ArgentinaFil: Madariaga, María Julia. Instituto de Zoonosis Luis Pasteur; ArgentinaFil: Dominguez, María Luz. Instituto de Zoonosis Luis Pasteur; ArgentinaFil: Teijeiro, María Luisa. Instituto de Zoonosis Luis Pasteur; ArgentinaFil: Fernandez, Natalia Mercedes. Instituto de Zoonosis Luis Pasteur; ArgentinaFil: Elena, Sebastián. Servicio Nacional de Sanidad y Calidad Agroalimentaria. Dirección General de Laboratorio y Control Técnico. Laboratorio de Referencia de la OIE para Brucelosis; ArgentinaFil: Trangoni, Marcos David. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular. ArgentinaFil: Trangoni, Marcos David. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Always the third rail?: pension income and policy preferences in European democracies

Social transfer programs are thought to generate beneficiary groups who will act politically to defend “their” programs from retrenchment. But little empirical research has been conducted to either verify or disconfirm the micro foundations of this hypothesis, which lies at the heart of the “new social risks” thesis as well as many economic analyses of welfare state politics. This article tests empirically whether benefiting from public pensions leads individuals to greater support of the pension system status quo, net of other factors. It uses cross—data set imputation to combine cross-nationally comparable individual-level data on income from public pensions with political attitudes toward proposed pension reforms. The hypothesis that public pension systems create policy feedbacks of self-interested beneficiaries supporting further pension spending is not supported in any of 11 European countries in either 1992 or 2001

From a Cone Snail Toxin to a Competitive MC4R Antagonist

International audienceThe melanocortin 4 receptor (MC4R) plays a role in energy homeostasis and represents a target for treating energy balance disorders. For decades, synthetic ligands have been derived from MC4R endogenous agonists and antagonists, such as setmelanotide used to treat rare forms of genetic obesity. Recently, animal venoms have demonstrated their capacity to provide melanocortin ligands with toxins from a scorpion and a spider. Here, we described a cone snail toxin, N-CTX-Ltg1a, with a nanomolar affinity for hMC4R but unrelated to any known toxins or melanocortin ligands. We then derived from the conotoxin the linear peptide HT1-0, a competitive antagonist of G s , G 15 , and β-arrestin2 pathways with a low nanomolar affinity for hMC4R. Similar to endogenous ligands, HT1-0 needs hydrophobic and basic residues to bind hMC4R. Altogether, it represents the first venom-derived peptide of high affinity on MC4R and paves the way for the development of new MC4R antagonists

A venomics approach coupled to high-throughput toxin production strategies identifies the first venom-derived melanocortin receptor agonists

Animal venoms are rich in hundreds of toxins with extraordinary biological activities. Their exploitation is difficult due to their complexity and the small quantities of venom available from most venomous species. We developed a Venomics approach combining transcriptomic and proteomic characterization of 191 species and identified 20,206 venom toxin sequences. Two complementary production strategies based on solid-phase synthesis and recombinant expression in Escherichia coli generated a physical bank of 3597 toxins. Screened on hMC4R, this bank gave an incredible hit rate of 8%. Here, we focus on two novel toxins: N-TRTX-Preg1a, exhibiting an inhibitory cystine knot (ICK) motif, and N-BUTX-Ptr1a, a short scorpion-CSαβ structure. Neither N-TRTX-Preg1a nor N-BUTX-Ptr1a affects ion channels, the known targets of their toxin scaffolds, but binds to four melanocortin receptors with low micromolar affinities and activates the hMC1R/Gs pathway. Phylogenetically, these two toxins form new groups within their respective families and represent novel hMC1R agonists, structurally unrelated to the natural agonists