Fungal opportunistic pathogens colonize various environments, from plants and wood to human and animal tissue. Regarding human pathogens, one great challenge during contrasting niche occupation is the adaptation to different conditions, such as temperature, osmolarity, salinity, pressure, oxidative stress and nutritional availability, which may constitute sources of stress that need to be tolerated and overcome. As an opportunistic pathogen, C. neoformans faces exactly these situations during the transition from the environment to the human host, encountering nutritional constraints. Our previous and current research on amino acid biosynthetic pathways indicates that amino acid permeases are regulated by the presence of the amino acids, nitrogen and temperature. Saccharomyces cerevisiae and Candida albicans have twenty-four and twenty-seven genes encoding amino acid permeases, respectively; conversely, they are scarce in number in Basidiomycetes (C. neoformans, Coprinopsis cinerea and Ustilago maydis), where nine to ten permease genes can be found depending on the species. In this study, we have demonstrated that two amino acid permeases are essential for virulence in C. neoformans. Our data showed that C. neoformans uses two global and redundant amino acid permeases, Aap4 and Aap5 to respond correctly to thermal and oxidative stress. Double deletion of these permeases causes growth arrest in C. neoformans at 37°C and in the presence of hydrogen peroxide. The inability to uptake amino acid at a higher temperature and under oxidative stress also led to virulence attenuation in vivo. Our data showed that thermosensitivity caused by the lack of permeases Aap4 and Aap5 can be remedied by alkaline conditions (higher pH) and salinity. Permeases Aap4 and Aap5 are also required during fluconazole stress and they are the target of the plant secondary metabolite eugenol, a potent antifungal inhibitor that targets amino acid permeases. In summary, our work unravels (i) interesting physiological property of C. neoformans regarding its amino acid uptake system; (ii) an important aspect of virulence, which is the need for amino acid permeases during thermal and oxidative stress resistance and, hence, host invasion and colonization; and (iii) provides a convenient prototype for antifungal development, which are the amino acid permeases Aap4/Aap5 and their inhibitor.

O Método Mãe Canguru (MC) é destinado ao atendimento do recém-nascido prematuro de baixo peso, e visa fortalecer o vínculo mãe-filho, aumentar a competência e a confiança dos pais no cuidado do bebê e incentivar a prática da amamentação. O objetivo do estudo foi demonstrar as evidências que apontam o uso de Método Canguru (MC) como uma alternativa aos cuidados neonatais, enfocando seus benefícios e avaliando se o método reduz a morbidade e mortalidade em neonatos de baixo peso. Trata-se de uma pesquisa descritiva, realizada a partir de um levantamento bibliográfico nas bases de dados BDEnf, Lilacs, SciELO e BIREME, considerando o período de 2000 a 2016. Foram analisados artigos sobre o Método Canguru (MC) e a redução da morbimortalidade neonatal. O estudo evidenciou que o Método Mãe Canguru (MC) reduz as taxas tanto de mortalidade como morbidade neonatal, porém demonstrou que existem poucos estudos referentes a este tema. O Método Mãe Canguru (MC) demonstrou ser mais que uma alternativa para países de baixa renda, nos quais faltam incubadoras ou salas de atendimento neonatal, constituindo-se, também, uma estratégia com múltiplas vantagens para o recém-nascido, tanto o prematuro quanto o nascido a termo. Destacou-se a eficácia do método na diminuição da morbimortalidade do neonato com baixo peso. Os estudos sobre mortalidade e morbidade do Método Mãe-Canguru (MC), em países de baixa e média renda, concluíram que o Método Mãe Canguru (MC) reduz, substancialmente, a mortalidade neonatal em bebês nascidos antes do termo com baixo peso em hospitais. Palavras-chave: Morbimortalidade Neonatal. Método Canguru. Recém-Nascido de Baixo Peso. Abstract: The Kangaroo Mother Method is intended for the care of the low weight premature newborn and aims to strengthen the mother-child bond, increase the parents’ competence and trust in the baby care and encourage the breastfeeding practice. The objective was  demonstrating the evidence supporting the use of KMM as an alternative to neonatal care, focusing on its benefits and evaluating whether the method reduces morbidity and mortality in low weight premature newborn. This is a descriptive research, based on a bibliographic survey in the databases BDEnf, Lilacs, SciELO and BIREME, considering the period from 2000 to 2016.  Articles were analyzed on the Kangaroo Method and the reduction of neonatal morbidity and mortality, the study showed that the Kangaroo Mother Method reduces the rates of both mortality and neonatal morbidity, but has shown that there are few studies related to this topic. The Kangaroo Mother Method has proven to be more than an alternative for low-income countries, where incubators or neonatal care rooms are lacking. It is also a strategy with multiple advantages for the newborn, both premature and full-term. The method efficacy in reducing neonatal morbidity and mortality and low weight was emphasized. Mortality and morbidity studies of the Kangaroo Method in low- and middle-income countries have concluded that the Kangaroo Mother Method substantially reduces neonatal mortality in preterm infants in hospitals and underweight. Keywords: Morbidity and Mortality Neonatal. Kangaroo Method. Low Birth Newborn.