Table of contents

Volume 10, Issue 2, pp. 18 - 48, February 2023

Issue cover
Cover: CD8 T-cells close to wound after a Staphylococcus epidermidis application: the T cells localize to sites of injury in skin following commensal colonization (image by the National Institute of Allergy and Infectious Diseases (NIAID), USA; image modified by MIC). The cover is published under the Creative Commons Attribution (CC BY) license. Enlarge issue cover

Research Articles

The role of invariant surface glycoprotein 75 in xenobiotic acquisition by African trypanosomes

Alexandr Makarov, Jakub Began, Ileana Corvo Mautone, Erika Pinto, Liam Ferguson, Martin Zoltner, Sebastian Zoll and Mark C. Field

page 18-35 | 10.15698/mic2023.02.790 | Full text | PDF | Abstract

The surface proteins of parasitic protozoa mediate functions essential to survival within a host, including nutrient accumulation, environmental sensing and immune evasion. Several receptors involved in nutrient uptake and defence from the innate immune response have been described in African trypanosomes and, together with antigenic variation, contribute towards persistence within vertebrate hosts. Significantly, a superfamily of invariant surface glycoproteins (ISGs) populates the trypanosome surface, one of which, ISG75, is implicated in uptake of the century-old drug suramin. By CRISPR/Cas9 knockout and biophysical analysis, we show here that ISG75 directly binds suramin and mediates uptake of additional naphthol-related compounds, making ISG75 a conduit for entry of at least one structural class of trypanocidal compounds. However, ISG75 null cells present only modest attenuation of suramin sensitivity, have unaltered viability in vivo and in vitro and no alteration to suramin-invoked proteome responses. While ISG75 is demonstrated as a valid suramin cell entry pathway, we suggest the presence of additional mechanisms for suramin accumulation, further demonstrating the complexity of trypanosomatid drug interactions and potential for evolution of resistance.

The first taxonomic and functional characterization of human CAVD-associated microbiota

Lavinia Curini, Brunilda Alushi, Mary Roxana Christopher, Simone Baldi, Leandro Di Gloria, Pierluigi Stefano, Anna Laganà, Luisa Iannone, Herko Grubitzsch, Ulf Landmesser, Matteo Ramazzotti, Elena Niccolai, Alexander Lauten and Amedeo Amedei

page 36-48 | 10.15698/mic2023.02.791 | Full text | PDF | Abstract

Introduction: Calcific aortic valve disease (CAVD) is the most common heart valve disorder, defined by a remodeling multistep process: namely, valve fibrosis with its area narrowing, impaired blood flow, and final calcification phase. Nowadays, the only treatment is the surgical valve replacement.
As for other cardiovascular diseases, growing evidence suggest an active role of the immune system in the calcification process that could be modulated by the microbiota. To address this point, we aimed to investigate and characterize, for the first time, the presence of a valve microbiota and associated immune response in human CAVD.
Method: Calcified aortic valve (CAV) samples from twenty patients (11 from Germany and 9 from Italy) with diagnosis of severe symptomatic CAVD were used to assess the presence of infiltrating T cells, by cloning approach, and to characterize the valve microbiota, by 16S rRNA gene sequencing (NGS).
Results: We documented the presence of infiltrating T lymphocytes, especially the T helper subset, in CAV samples. Moreover, we found a tissue-associated microbiota in freshly collected CAV samples, which was significantly different in Italian and German patients, suggesting potential correlation with other cardiovascular risk factors.
Conclusion: The presence of microbiota in inflamed CAV samples represents the right trigger point to explain the valve calcification process, encouraging further studies to explore the potential link between bacteria and adaptive immune response and to define the critical role of local microbiota-immunity axis on CAVD development.

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