RESUMO
Members of the Paracoccidioides complex are the causative agents of Paracoccidioidomycosis (PCM), a human systemic mycosis endemic in Latin America. Upon initial contact with the host, the pathogen needs to uptake micronutrients. Nitrogen is an essential source for biosynthetic pathways. Adaptation to nutritional stress is a key feature of fungi in host tissues. Fungi utilize nitrogen sources through Nitrogen Catabolite Repression (NCR). NCR ensures the scavenging, uptake and catabolism of alternative nitrogen sources, when preferential ones, such as glutamine or ammonium, are unavailable. The NanoUPLC-MSE proteomic approach was used to investigate the NCR response of Paracoccidioides lutzii after growth on proline or glutamine as a nitrogen source. A total of 338 differentially expressed proteins were identified. P. lutzii demonstrated that gluconeogenesis, ß-oxidation, glyoxylate cycle, adhesin-like proteins, stress response and cell wall remodeling were triggered in NCR-proline conditions. In addition, within macrophages, yeast cells trained under NCR-proline conditions showed an increased ability to survive. In general, this study allows a comprehensive understanding of the NCR response employed by the fungus to overcome nutritional starvation, which in the human host is represented by nutritional immunity. In turn, the pathogen requires rapid adaptation to the changing microenvironment induced by macrophages to achieve successful infection.
RESUMO
Fungal infections represent a serious global health problem, causing damage to health and the economy on the scale of millions. Although vaccines are the most effective therapeutic approach used to combat infectious agents, at the moment, no fungal vaccine has been approved for use in humans. However, the scientific community has been working hard to overcome this challenge. In this sense, we aim to describe here an update on the development of fungal vaccines and the progress of methodological and experimental immunotherapies against fungal infections. In addition, advances in immunoinformatic tools are described as an important aid by which to overcome the difficulty of achieving success in fungal vaccine development. In silico approaches are great options for the most important and difficult questions regarding the attainment of an efficient fungal vaccine. Here, we suggest how bioinformatic tools could contribute, considering the main challenges, to an effective fungal vaccine.
RESUMO
Systemic mycoses have been viewed as neglected diseases and they are responsible for deaths and disabilities around the world. Rapid, low-cost, simple, highly-specific and sensitive diagnostic tests are critical components of patient care, disease control and active surveillance. However, the diagnosis of fungal infections represents a great challenge because of the decline in the expertise needed for identifying fungi, and a reduced number of instruments and assays specific to fungal identification. Unfortunately, time of diagnosis is one of the most important risk factors for mortality rates from many of the systemic mycoses. In addition, phenotypic and biochemical identification methods are often time-consuming, which has created an increasing demand for new methods of fungal identification. In this review, we discuss the current context of the diagnosis of the main systemic mycoses and propose alternative approaches for the identification of new targets for fungal pathogens, which can help in the development of new diagnostic tests.
RESUMO
Fungi of the Paracoccidioides genus are the etiological agents of paracoccidioidomycosis (PCM), a systemic mycosis restricted to the countries of Latin America. Currently, the Paracoccidioides complex is represented by Paracoccidioides lutzii, Paracoccidioides americana, Paracoccidioides brasiliensis, Paracoccidioides restrepiensis, and Paracoccidioides venezuelensis. Even with advances in techniques used for diagnosing fungal diseases, high rates of false-positive results for PCM are still presented. Additionally, there is no efficient antigen that can be used to follow up the efficiency of patient treatment. The immunoproteomic is considered a powerful tool for the identification of antigens. In addition, antigens are molecules recognized by the immune system, which make them excellent targets for diagnostic testing of diseases caused by microorganisms. In this vein, we investigated which antigens are secreted by species representing Paracoccidioides complex to increase the spectrum of molecules that could be used for future diagnostic tests, patient follow-up, or PCM therapy. To identify the profile of antigens secreted by Paracoccidioides spp., immunoproteomic approaches were used combining immunoprecipitation, followed by antigen identification by nanoUPLC-MSE-based proteomics. Consequently, it was possible to verify differences in the exoantigen profiles present among the studied species. Through a mass spectrometry approach, it was possible to identify 79 exoantigens in Paracoccidioides species. Using bioinformatics tools, two unique exoantigens in P. lutzii species were identified, as well as 44 epitopes exclusive to the Paracoccidioides complex and 12 unique antigenic sequences that can differentiate between Paracoccidioides species. Therefore, these results demonstrate that Paracoccidioides species have a range of B-cell epitopes exclusive to the complex as well as specific to each Paracoccidioides species. In addition, these analyses allowed us the identification of excellent biomarker candidates for epidemiology screening, diagnosis, patient follow-up, as well as new candidates for PCM therapy.
RESUMO
Os micro-organismos que apresentam mecanismos de resistência aos antimicrobianos, como produção de ß-lactamase de espectro estendido (ESBL), resultam em uma maior dificuldade no tratamento e exigem a utilização de antibióticos de largo espectro com frequência crescente. Assim, este estudo busca revisar a literatura sobre as infecções causadas por micro-organismos multirresistentes na gravidez. Foi realizada uma busca de artigos no PubMed, MedLine e Lilacs usando-se unitermos, incluindo-se os estudos publicados de 2000 a 2016, de línguas portuguesa e inglesa, envolvendo apenas seres humanos. Foram selecionados 59 artigos com força de evidência A e B. Os critérios para inclusão no estudo são: estarem grávidas e terem diagnóstico de infecção do trato urinário. Serão critérios de exclusão: uso de antimicrobiano a menos de duas semanas antes da coleta da amostra e portadoras de doença imunossupressora. A verdadeira prevalência de ITU em gestantes por bactérias multirresistentes é desconhecida. As ITUs por bactérias produtoras de ESBL variam entre 1% e 40%. O tratamento mais aceito para os casos mais graves (pielonefrite ou bacteremia) é com carbapenêmicos. A nitrofurantoína e a fosfomicina têm sido utilizadas para tratar a cistite com patógenos produtores de ESBL com sucesso.(AU)
Microorganisms that have resistance mechanisms to antimicrobial agents, such as production of ß-lactamase extended spectrum (ESBL), result in greater difficulty in treatment and require the use of broad spectrum antibiotics with increasing frequency. This study aims to review the literature on infections caused by multiresistant microorganisms in pregnancy. A search for articles was conducted in PubMed, MedLine and Lilacs are using key words, including published studies from 2000 to 2016, Portuguese and English, involving only human. 59 articles were selected on strength of evidence A and B. The criteria for inclusion was pregnant and having diagnosed of urinary tract infection. The criteria for exclusion was: use of antimicrobial less than two weeks before sample collection and suffering from immunosuppressive disease. The true prevalence of UTI in pregnant women by multiresistant bacteria is unknown. UTIs for ESBL-producing bacteria, ranging from 1% to 40%. The treatment more acceptable for the most serious cases (pyelonephritis or bacteremia) is with carbapenems. Nitrofurantoin and fosfomycin has been used to treat successfully with cystitis ESBL producers pathogens.(AU)