Pseudomonas aeruginosa and Staphylococcus aureus communication in biofilm infections: insights through network and database construction

AbstractThe polymicrobial nature of most infections is often characterized by complex biofilm communities, where pathogen interactions promote infection progression and severity. Quorum-sensing, the major regulator of virulence and inter-species communication, is a promising target for new anti-infective strategies. This study aimed at collecting and analysing experimental information on the molecular basis of Pseudomonas aeruginosa and Staphylococcus aureus interactions in biofilms. Data were systematically annotated from relevant full-text papers optimally retrieved from PubMed, reconstructed as networks and integrated with specialized databases to identify promising antimicrobial targets. Network analysis revealed key entities regulating P. aeruginosa/S. aureus interactions, for instance the PqsABCDE/PqsR quorum-sensing system, which affects S. aureus growth and biofilm formation. By identifying the most reported P. aeruginosa virulence factors affecting S. aureus, for example, HQNO and siderophores, a list of experimentally validated agents affecting those factors, ranging from synthetic drugs to natural plant extracts, was constructed. The complex experimental data on P. aeruginosa/S. aureus interactions were for the first time systematically organized and made publically available in the new Inter-Species CrossTalk Database (www.ceb.uminho.pt/ISCTD).This work was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2019 unit; the European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte for the BioTecNorte operation (NORTE-01-0145-FEDER-000004); the COMPETE2020 and the FCT under the scope of the project POCI-01-0145-FEDER-029841; and the FCT under the scope of the PhD Grant of Andreia Patricia Magalhães [grant number SFRH/BD/132165/2017].info:eu-repo/semantics/publishedVersio

Deciphering the role of Staphylococcus aureus in Pseudomonas aeruginosa adaptation to cystic fibrosis lungs: bystander or intervener?

Microbiotec'17 - Congress of Microbiology and Biotechnology 2017Background: Pseudomonas aeruginosa is the major responsible for the high mortality rate of cystic fibrosis (CF) patients due to the development of chronic infections. To long persist, P. aeruginosa uses sophisticated mechanisms to achieve fulladaptation, mainly triggered by the harsh environmental conditions of CF lungs. The influence of Staphylococcus aureus, a primary colonizer of CF lungs, in increasing P. aeruginosa pathogenicity has also been reported. The main objective of this study was to decipher the impact of S. aureus on P. aeruginosa pathogenicity using in vitro conditions mimicking CF lungs. [...]This study was supported by the FCT (UID/BIO/04469/2013), COMPETE 2020 (POCI-01-0145-FEDER-006684) and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte.info:eu-repo/semantics/publishedVersio

Pitfalls associated with discriminating mixed-species biofilms by flow cytometry

Since biofilms are ubiquitous in different settings and act as sources of disease for humans, reliable methods to characterize and quantify these microbial communities are required. Numerous techniques have been employed, but most of them are unidirectional, labor intensive and time consuming. Although flow cytometry (FCM) can be a reliable choice to quickly provide a multiparametric analysis, there are still few applications on biofilms, and even less on the study of inter-kingdom communities. This work aimed to give insights into the application of FCM in order to more comprehensively analyze mixed-species biofilms, formed by different Pseudomonas aeruginosa and Candida albicans strains, before and after exposure to antimicrobials. For comparison purposes, biofilm culturability was also assessed determining colony-forming units. The results showed that some aspects, namely the microbial strain used, the morphological state of the cells and the biofilm matrix, make the accurate analysis of FCM data difficult. These aspects were even more challenging when double-species biofilms were being inspected, as they could engender data misinterpretations. The outcomes draw our attention towards the need to always take into consideration the characteristics of the biofilm samples to be analyzed through FCM, and undoubtedly link to the need for optimization of the processes tailored for each particular case study.This work was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of the UID/BIO/04469/2020 unit and BioTecNorte operation (NORTE-01-0145-FEDER-000004), which was funded by the European Regional Development Fund under the scope of Norte2020–Programa Operacional Regional do Norte. The authors also acknowledge COMPETE2020 and FCT under the project POCI-01-0145-FEDER-029841 and FCT for the PhD grant to Tânia Grainha (grant number SFRH/BD/136544/2018).info:eu-repo/semantics/publishedVersio

Novel liposomes for Alzheimers disease treatment

This work was supported by the strategic programme UID/BIA/04050/2019, funded by national funds through the FCT IP, and project FUN2CYT: Harnessing the potential for biomedical applications of pleiotropic cytokines LIF and oncostatin M (PTDC/BTM-MAT/30568/2017, POCI-01-0145-FEDER-030568) supported by POCI through FEDER and FCT IP.info:eu-repo/semantics/publishedVersio

Antimicrobial resistance three ways: healthcare crisis, major concepts, and the relevance of biofilms

Worldwide, infections are resuming their role as highly effective killing diseases, as current treatments are failing to respond to the growing problem that is antimicrobial resistance (AMR). The social and economical burden of AMR seems ever rising, with health- and research-related organizations rushing to collaborate on a worldwide scale to find effective solutions. Resistant bacteria are spreading even in first-world nations, being found not only in healthcare-related settings, but also in food and in the environment. In this mini-review, the impact of AMR in healthcare systems and the major bacteria behind it are highlighted. Ecological aspects of AMR evolution and the complexity of its molecular mechanisms are explained. Major concepts, such as intrinsic, acquired, and adaptive resistance, as well as tolerance and heteroresistance, are also clarified. More importantly, the problematic of biofilms and their role in AMR, namely its main resistance and tolerance mechanisms, is elucidated. Finally, some of the most promising anti-biofilm strategies being investigated are reviewed. Much is still to be done regarding the study of AMR and the discovery of new anti-biofilm strategies. Gladly, considerable research on this topic is generated every day and increasingly concerted actions are being engaged globally to try and tackle this problem.This work was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2019 unit and COMPETE 2020 (POCI-01-0145-FEDER-006684) and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte. The authors also acknowledge COMPETE2020 and FCT for the project POCI-01-0145-FEDER-029841, and FCT for the PhD Grants of Andreia Magalhães [grant number SFRH/BD/132165/2017] and Tânia Grainha [grant number SFRH/BD/136544/2018].info:eu-repo/semantics/publishedVersio

Impact of combined training with different exercise intensities on inflammatory and lipid markers in type 2 diabetes : a secondary analysis from a 1-year randomized controlled trial

© The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creat ivecommons .org/licen ses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creat iveco mmons .org/publi cdoma in/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.Background: Exercise is a well-accepted strategy to improve lipid and infammatory profle in individuals with type 2 diabetes (T2DM). However, the exercise intensity having the most benefts on lipids and infammatory markers in patients with T2DM remains unclear. We aimed to analyse the impact of a 1-year combined high-intensity interval training (HIIT) with resistance training (RT), and a moderate continuous training (MCT) with RT on infammatory and lipid profle in individuals with T2DM. Methods: Individuals with T2DM (n=80, aged 59 years) performed a 1-year randomized controlled trial and were randomized into three groups (control, n=27; HIIT with RT, n=25; MCT with RT, n=28). Exercise sessions were super‑ vised with a frequency of 3 days per week. Infammatory and lipid profles were measured at baseline and at 1-year follow-up. Changes in infammatory and lipid markers were assessed using generalized estimating equations. Results: After adjusting for sex, age and baseline moderate-to-vigorous physical activity (MVPA), we observed a time-by-group interaction for Interleukin-6 (IL-6) in both the MCT with RT (β=−0.70, p=0.034) and HIIT with RT (β=−0.62, p=0.049) groups, whereas, only the HIIT with RT group improved total cholesterol (β=−0.03, p=0.045) and LDL-C (β=−0.03, p=0.034), when compared to control. No efect was observed for C-reactive protein (CRP), cortisol, tumour necrosis factor-α (TNF-α), soluble form of the haptoglobin-hemoglobin receptor CD163 (sCD163), triglycerides and HDL-C in both groups (p>0.05). Conclusions: Favorable adaptations on IL-6 were observed in both the HIIT and MCT combined with RT groups fol‑ lowing a long-term 1-year exercise intervention in individuals with T2DM. However, only the HIIT with RT prevented further derangement of total cholesterol and LDL-C, when compared to the control group. Therefore, in order to encourage exercise participation and improve infammatory profle, either exercise protocols may be prescribed, however, HIIT with RT may have further benefts on the lipid profle.This work was supported by fellowships from the Portuguese Foundation for Science and Technology (JM grant: SFRH/BD/85742/2012; IRC grant: IRC: SFRH/BD/149394/2019). This work is also fnanced by a national grant through the FCT–Fundação para a Ciência e Tecnologia within the unit I&D 447 (UIDB/00447/2020).info:eu-repo/semantics/publishedVersio

Exclusion of mutations in the PRNP, JPH3, TBP, ATN1, CREBBP, POU3F2 and FTL genes as a cause of disease in Portuguese patients with a Huntington-like phenotype

Huntington disease (HD) is an autosomal dominant neurodegenerative disorder characterised by chorea, cognitive impairment, dementia and personality changes, caused by the expansion of a CAG repeat in the HD gene. Often, patients with a similar clinical presentation do not carry expansions of the CAG repeat in this gene [Huntington disease-like (HDL) patients]. We report the genetic analysis of 107 Portuguese patients with an HDL phenotype. The HDL genes PRNP and JPH3, encoding the prion protein and junctophilin-3, respectively, were screened for repeat expansions in these patients. Given the partial clinical overlap of SCA17, DRPLA and neuroferritinopathy with HD, their causative genes (TBP, ATN1, and FTL, respectively) were also analysed. Finally, repeat expansions in two candidate genes, CREBBP and POU3F2, which encode the nuclear transcriptional coactivator CREB-binding protein and the CNS-specific transcription factor N-Oct-3, respectively, were also studied. Expansions of the repetitive tracts of the PRNP, JPH3, TBP, ATN1, CREBBP and POU3F2 genes were excluded in all patients, as were sequence alterations in the FTL gene. Since none of the genes already included in the differential diagnosis of HD was responsible for the disease in our sample, the genetic heterogeneity of the HDL phenotype is still open for investigation.Fundação para a Ciência e a Tecnologia (FCT) and FEDER (grant CBO/33485/99). BIC included in grant CBO/33485/99, respectivel

Whole-genome sequencing of 1,171 elderly admixed individuals from Brazil

As whole-genome sequencing (WGS) becomes the gold standard tool for studying population genomics and medical applications, data on diverse non-European and admixed individuals are still scarce. Here, we present a high-coverage WGS dataset of 1,171 highly admixed elderly Brazilians from a census-based cohort, providing over 76 million variants, of which ~2 million are absent from large public databases. WGS enables identification of ~2,000 previously undescribed mobile element insertions without previous description, nearly 5 Mb of genomic segments absent from the human genome reference, and over 140 alleles from HLA genes absent from public resources. We reclassify and curate pathogenicity assertions for nearly four hundred variants in genes associated with dominantly-inherited Mendelian disorders and calculate the incidence for selected recessive disorders, demonstrating the clinical usefulness of the present study. Finally, we observe that whole-genome and HLA imputation could be significantly improved compared to available datasets since rare variation represents the largest proportion of input from WGS. These results demonstrate that even smaller sample sizes of underrepresented populations bring relevant data for genomic studies, especially when exploring analyses allowed only by WGS

práticas artísticas no ensino básico e secundário

Para este número 18 da Revista Matéria-Prima reuniram-se 16 artigos que permitem colocar em perspetiva diversas dimensões da Educação Artística. Entre a consciência patrimonial e a emancipação, entre o domínio da técnica e do género, entre a integração e a maturação criadora, há um espaço a ser pesquisado, feito de história, de identidade, de ensaio e de inclusividadeinfo:eu-repo/semantics/publishedVersio

The cystic fibrosis microbiome in an ecological perspective and its impact in antibiotic therapy

The recent focus on the cystic fibrosis (CF) complex microbiome has led to the recognition that the microbes can interact between them and with the host immune system, affecting the disease progression and treatment routes. Although the main focus remains on the interactions between traditional pathogens, growing evidence supports the contribution and the role of emergent species. Understanding the mechanisms and the biological effects involved in polymicrobial interactions may be the key to improve effective therapies and also to define new strategies for disease control. This review focuses on the interactions between microbe-microbe and host-microbe, from an ecological point of view, discussing their impact on CF disease progression. There are increasing indications that these interactions impact the success of antimicrobial therapy. Consequently, a new approach where therapy is personalized to patients by taking into account their individual CF microbiome is suggested.Portuguese Foundation for Science and Technology (FCT), the strategic funding of UID/BIO/04469/2013-CEB and UID/EQU/00511/2013-LEPABE units. This study was also supported by FCT and the European Community fund FEDER, through Program COMPETE, under the scope of the Projects “DNA mimics” PIC/IC/82815/2007, RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462), “BioHealth—Biotechnology and Bioengineering approaches to improve health quality”, Ref. NORTE-07-0124-FEDER-000027 and NORTE-07-0124-FEDER-000025—RL2_ Environment and Health, co-funded by the Programa Operacional Regional do Norte (ON.2 – O Novo Norte), QREN, FEDER. The authors also acknowledge the grant of Susana P. Lopes (SFRH/BPD/95616/2013) and of the COST-Action TD1004: Theragnostics for imaging and therapy