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Duarte, I. F.

Publications and source records attributed to Duarte, I. F..

2 recordsLinked to original sources

Camel urine limits proliferation and modifies cell morphology in human renal tumoral and non-tumoral cells

The widespread ethnomedical practice of dromedary urinotherapy as a remedy against various illnesses is well recognized in traditional dromedary countries, and multiple researchers tried to unravel its bioactive potential and provide scientific evidence through in vivo and in vitro experiments. None of these studies (i) measured urine osmolarity prior to bioactivity testing, which could deeply influence the results of in vitro tests, nor (ii) addressed issues related to cells morphological changes after exposure to camel urines. Taken together, the above aspects point to the need for a "good practice" to be shared by researchers in this field, in order to reduce the variability of in vitro testing of camel urine bioactivity. In this work, using a set of biological samples from animals differing in sex, age, and physiological status, we investigated, the antiproliferative activity of camel urine towards human non-tumoral (HK2) and tumoral renal cells (Caki-1), through cell viability and microscopy analysis, and taking the possible influence of osmolarity into account. We employed cell lines commonly used in toxicological research which, to the best of our knowledge, have not been previously exposed to camel urine. HK2 and Caki-1 cells tolerated well mannitol-induced hyperosmolarity up to 500 mOsm/L. Significant antiproliferative effects were observed only in Caki-1 cells, when exposed to urine solutions (diluted to <500 mOsm/L) from two males out of the ten tested samples, while effects on cell morphology (elongation) were observed only in HK2 cells, when exposed to urine solutions from six samples. The significant antiproliferative effect observed only in tumoral cells looks promising for forthcoming developments in the cancer treatment field. Finally, the presented approach may serve as a guide for future research in this specific, multidisciplinary field.

cell biology↗

Aspergillus fumigatus acetate utilisation impacts virulence traits and pathogenicity

Aspergillus fumigatus is a major opportunistic fungal pathogen of immunocompromised and immunocompetent hosts. To successfully establish an infection, A. fumigatus needs to use host carbon sources, such as acetate, present in the body fluids and peripheral tissues. However, utilisation of acetate as a carbon source by fungi in the context of infection has not been investigated. This work shows that acetate is metabolised via different pathways in A. fumigatus and that acetate utilisation is under the regulatory control of a transcription factor (TF), FacB. A. fumigatus acetate utilisation is subject to carbon catabolite repression (CCR), although this is only partially dependent on the TF and main regulator of CCR CreA. The available extracellular carbon source, in this case glucose and acetate, significantly affected A. fumigatus virulence traits such as secondary metabolite secretion and cell wall composition, with the latter having consequences for resistance to oxidative stress, to anti-fungal drugs and to human neutrophil-mediated killing. Furthermore, deletion of facB significantly impaired the in vivo virulence of A. fumigatus in both insect and mammalian models of invasive aspergillosis. This is the first report on acetate utilisation in A. fumigatus and this work further highlights the importance of available host-specific carbon sources in shaping fungal virulence traits and subsequent disease outcome, and a potential target for the development of anti-fungal strategies. ImportanceAspergillus fumigatus is an opportunistic fungal pathogen in humans. During infection, A. fumigatus is predicted to use host carbon sources, such as acetate, present in body fluids and peripheral tissues, to sustain growth and promote colonisation and invasion. This work shows that A. fumigatus metabolises acetate via different pathways, a process that is dependent on the transcription factor FacB. Furthermore, the type and concentration of the extracellular available carbon source were determined to shape A. fumigatus virulence determinants such as secondary metabolite secretion and cell wall composition. Subsequently, interactions with immune cells are altered in a carbon source-specific manner. FacB is required for A. fumigatus in vivo virulence in both insect and mammalian models of invasive aspergillosis. This is the first report that characterises acetate utilisation in A. fumigatus and highlights the importance of available host-specific carbon sources in shaping virulence traits and potentially subsequent disease outcome.

microbiology↗