Ferreira, Marina & Gonçalves, Diego & Medeiros, Elisa & Peralta, José Mauro & Guimaraes, Allan. (2021). “Feast-Fit-Fist-Feat”: Overview of Free-living Amoeba Interactions with Fungi and Virulence as a Foundation for Success in Battle. Current Tropical Medicine Reports. 8.

DOI: https://link.springer.com/article/10.1007/s40475-020-00220-3

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Free-living amoebae (FLAs) are ubiquitous and can co-habit similar niches and interact with fungi. Herein, we discuss theories on FLAs and the origin, evolution, and conservation of fungal virulence, proposing the “feast-fit-fist-feat” hypothesis that covers the knowledge on FLA-fungi interactions, and could be extended during evolutionarily host escalation. Overall, by bridling this selective pressure, fungi might return to environment and by serendipity, infect superior hosts. The selected traits might grant the fungus with an enhanced capacity to cause damage, or virulence. The fungal virulence factors that might be expressed during infection to amoeba and that grant a fungal benefit during infection to mammals are discussed. However, how they are induced during infection of FLAs is still an open field. Here we discuss also the “Trojan Horse” role of FLAs and the importance of co-infections and disease outcome.

Firmino-Cruz L, Ramos TD, da Fonseca-Martins AM, Oliveira-Maciel D, Oliveira-Silva G, Dos Santos JS, Cavazzoni C, Morrot A, Gomes DCO, Vale AM, Decoté-Ricardo D, Freire-de-Lima CG, de Matos Guedes HL. B-1 lymphocytes are able to produce IL-10, but is not pathogenic during Leishmania (Leishmania) amazonensis infection. Immunobiology. 2020 Jan;225(1):151857.

DOI: 10.1016/j.imbio.2019.10.006

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Over the years research has found an association between B lymphocytes and pathogenesis during Leishmania sp. infections. Recently we demonstrated that B-2 lymphocytes are the main producers of IL-10 during L. amazonensis infection, and that the disease severity in BALB/c mice was attributed to these IL-10-producing B-2 lymphocytes. Here, we aim to understand the role of peritoneal B-1 lymphocytes in the pathogenesis of L. amazonensis infection. We found that infection resulted in a decrease in the number of B-1a lymphocytes and increase in B-1b lymphocytes in the peritoneal cavity of WT BALB/c mice but not in B lymphocyte deficient mice (BALB/Xid) mice. In vitro interaction between B-1 lymphocytes and L. amazonensis showed that the amastigote form of the parasite was able to induce higher levels of IL-10 in B-1 lymphocytes derived from infected BALB/c mice than the promastigote. Moreover, B-1 lymphocytes derived from infected mice produced more IL-10 than B-1 lymphocytes derived from naïve mice under amastigote interaction. However, the repopulation of BALB/Xid mice with B-1 lymphocytes from WT BALB/c mice did not affect the lesion development. Together, these results suggest that although B-1 lymphocytes are able to produce IL-10 during in vitro interaction with L. amazonensis, they are not directly related to pathogenesis in vivo.

Fintelman-Rodrigues N, Sacramento CQ, Ribeiro Lima C, Souza da Silva F, Ferreira AC, Mattos M, de Freitas CS, Cardoso Soares V, da Silva Gomes Dias S, Temerozo JR, Miranda MD, Matos AR, Bozza FA, Carels N, Alves CR, Siqueira MM, Bozza PT, Souza TML. Atazanavir, Alone or in Combination with Ritonavir, Inhibits SARS-CoV-2 Replication and Proinflammatory Cytokine Production. Antimicrob Agents Chemother. 2020 Sep 21;64(10):e00825-20.

DOI: https://doi.org/10.1128/aac.00825-20

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is already responsible for far more deaths than previous pathogenic coronaviruses (CoVs) from 2002 and 2012. The identification of clinically approved drugs to be repurposed to combat 2019 CoV disease (COVID-19) would allow the rapid implementation of potentially life-saving procedures. The major protease (Mpro) of SARS-CoV-2 is considered a promising target, based on previous results from related CoVs with lopinavir (LPV), an HIV protease inhibitor. However, limited evidence exists for other clinically approved antiretroviral protease inhibitors. Extensive use of atazanavir (ATV) as antiretroviral and previous evidence suggesting its bioavailability within the respiratory tract prompted us to study this molecule against SARS-CoV-2. Our results show that ATV docks in the active site of SARS-CoV-2 Mpro with greater strength than LPV, blocking Mpro activity. We confirmed that ATV inhibits SARS-CoV-2 replication, alone or in combination with ritonavir (RTV) in Vero cells and a human pulmonary epithelial cell line. ATV/RTV also impaired virus-induced enhancement of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) levels. Together, our data strongly suggest that ATV and ATV/RTV should be considered among the candidate repurposed drugs undergoing clinical trials in the fight against COVID-19.

Albuquerque SO, Barros TG, Dias LRS, Lima CHDS, Azevedo PHRA, Flores-Junior LAP, Dos Santos EG, Loponte HF, Pinheiro S, Dias WB, Muri EMF, Todeschini AR. Biological evaluation and molecular modeling of peptidomimetic compounds as inhibitors for O-GlcNAc transferase (OGT). Eur J Pharm Sci. 2020 Nov 1;154:105510.

DOI: https://doi.org/10.1016/j.ejps.2020.105510

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The vital enzyme O-linked β-N-acetylglucosamine transferase (OGT) catalyzes the O-GlcNAcylation of intracellular proteins coupling the metabolic status to cellular signaling and transcription pathways. Aberrant levels of O-GlcNAc and OGT have been linked to metabolic diseases as cancer and diabetes. Here, a new series of peptidomimetic OGT inhibitors was identified highlighting the compound LQMed 330, which presented better IC50 compared to the most potent inhibitors found in the literature. Molecular modeling study of selected inhibitors into the OGT binding site provided insight into the behavior by which these compounds interact with the enzyme. The results obtained in this study provided new perspectives on the design and synthesis of highly specific OGT inhibitors.