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Microorganisms
Special Issues
Exploring Host-Pathogen Interactions – Host-Directed Therapies
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Exploring Host-Pathogen Interactions – Host-Directed Therapies

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Medical Microbiology".

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 6099

Special Issue Editors

Dr. Ana Paula Arez

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Guest Editor
Global Health and Tropical Medicine (GHTM), Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa (UNL), 1349-008 Lisbon, Portugal
Interests: biological sciences; health sciences; infectious diseases; malaria; parasite–host interactions
Special Issues, Collections and Topics in MDPI journals
Dr. Marcia Medeiros

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Guest Editor
Global Health and Tropical Medicine, Instituto de Higiene e Medicina Tropical, Universidade NOVA de Lisboa, Lisboa, Portugal
Interests: malaria; low-density malaria infections; host-directed therapies; host–pathogen interactions; immunity

Special Issue Information

Dear Colleagues,

Human organisms are constantly exposed to microorganisms, and most have no effects on their health, with disease being an exception, not the rule. However, when host–microorganism interaction results in damage to the host, the microorganism becomes a pathogen. A kind of “war” begins when they meet, and the increasing incidence of treatment-resistant infections makes the need for alternative management strategies an urgent one.

By natural selection, hosts acquire strategies to deceive pathogens, and pathogens acquire strategies to overcome the defense mechanisms of the host and establish their life cycles. Most of the infectious agents identified as pathogens for humans cause disease in a subset of the population and circulate in another subset of individuals without producing apparent clinical symptoms. Understanding the mechanisms involved in human innate determinants of susceptibility or resistance against infection or the disease may help to intervene in host metabolic pathways vital to pathogen survival and find new tools that could act via a host-mediated response rather than acting directly on the pathogen. Their co-delivery with a traditional antimicrobial agent may help to circumvent drug resistance.

The aim of this Special Issue is to highlight processes and mechanisms involved in the crosstalk between infectious agents and hosts that are already used or that may potentially be adapted in the future to host-directed therapy (HDT) strategies. We invite you to submit research articles, reviews, or short communications that together may contribute to improving the knowledge about this promising approach.

Dr. Ana Paula Arez
Dr. Marcia Medeiros
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Microorganisms is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • microbe
  • pathogen
  • virus
  • bacteria
  • parasite
  • fungi
  • infection
  • disease
  • interaction
  • metabolism
  • host response
  • innate cell defenses
  • host susceptibility
  • host resistance
  • host-directed therapy

Published Papers (2 papers)

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Research

17 pages, 1431 KiB  
Article
Red Blood Cell BCL-xL Is Required for Plasmodium falciparum Survival: Insights into Host-Directed Malaria Therapies
by Coralie Boulet, Ghizal Siddiqui, Taylah L. Gaynor, Christian Doerig, Darren J. Creek and Teresa G. Carvalho
Microorganisms 2022, 10(4), 824; https://doi.org/10.3390/microorganisms10040824 - 15 Apr 2022
Cited by 4 | Viewed by 2571
Abstract
The development of antimalarial drug resistance is an ongoing problem threatening progress towards the elimination of malaria, and antimalarial treatments are urgently needed for drug-resistant malaria infections. Host-directed therapies (HDT) represent an attractive strategy for the development of new antimalarials with untapped targets [...] Read more.
The development of antimalarial drug resistance is an ongoing problem threatening progress towards the elimination of malaria, and antimalarial treatments are urgently needed for drug-resistant malaria infections. Host-directed therapies (HDT) represent an attractive strategy for the development of new antimalarials with untapped targets and low propensity for resistance. In addition, drug repurposing in the context of HDT can lead to a substantial decrease in the time and resources required to develop novel antimalarials. Host BCL-xL is a target in anti-cancer therapy and is essential for the development of numerous intracellular pathogens. We hypothesised that red blood cell (RBC) BCL-xL is essential for Plasmodium development and tested this hypothesis using six BCL-xL inhibitors, including one FDA-approved compound. All BCL-xL inhibitors tested impaired proliferation of Plasmodium falciparum 3D7 parasites in vitro at low micromolar or sub-micromolar concentrations. Western blot analysis of infected cell fractions and immunofluorescence microscopy assays revealed that host BCL-xL is relocated from the RBC cytoplasm to the vicinity of the parasite upon infection. Further, immunoprecipitation of BCL-xL coupled with mass spectrometry analysis identified that BCL-xL forms unique molecular complexes with human μ-calpain in uninfected RBCs, and with human SHOC2 in infected RBCs. These results provide interesting perspectives for the development of host-directed antimalarial therapies and drug repurposing efforts. Full article
(This article belongs to the Special Issue Exploring Host-Pathogen Interactions – Host-Directed Therapies)
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11 pages, 3768 KiB  
Communication
Titan Cells and Yeast Forms of Cryptococcus neoformans and Cryptococcus gattii Are Recognized by GXMR-CAR
by Matheus Henrique dos Santos, Michele Procópio Machado, Pappanaicken R. Kumaresan and Thiago Aparecido da Silva
Microorganisms 2021, 9(9), 1886; https://doi.org/10.3390/microorganisms9091886 - 5 Sep 2021
Cited by 8 | Viewed by 2785
Abstract
Cryptococcosis, a systemic mycosis that affects both the immunocompromised and immunocompetent, is caused by the inhalation of dehydrated yeasts or fungal spores of Cryptococcus gattii or Cryptococcus neoformans. The Cryptococcus spp. polysaccharide capsule is composed mainly of glucuronoxylomannan—GXM, its major virulence factor. [...] Read more.
Cryptococcosis, a systemic mycosis that affects both the immunocompromised and immunocompetent, is caused by the inhalation of dehydrated yeasts or fungal spores of Cryptococcus gattii or Cryptococcus neoformans. The Cryptococcus spp. polysaccharide capsule is composed mainly of glucuronoxylomannan—GXM, its major virulence factor. The capsule thickness increases to more than 15 μm during titanization, favoring the pathogenesis of cryptococcosis. Previous studies demonstrated that cytotoxic T cells that had been bioengineered with GXM-targeting chimeric antigen receptor (GXMR-CAR) were able to recognize C. neoformans by promoting the control of titanization. GXMR-CAR, a second-generation CAR, contains a single-chain variable fragment that originates from a 18B7 clone: a human IgG4 hinge, followed by a human CD28 (transmembrane/cytoplasmic domains) and a CD3ς chain. In the current study, we redirected T cells to target distinct C. neoformans and C. gattii cell types by GXMR-CAR. Lentiviral particles carrying the GXMR-CAR sequence were used to transduce Jurkat cells, and these modified cells interacted with the GXM of the C. gattii R265 strain. Moreover, GXMR-CAR mediated the recognition of C. gattii and C. neoformans yeasts with both thin and thick polysaccharide capsules, and GXMR-CAR Jurkat cells interacted with titan cells sourced from both Cryptococcus spp. Thus, bioengineered cells using CAR can improve the treatment of cryptococcosis. Full article
(This article belongs to the Special Issue Exploring Host-Pathogen Interactions – Host-Directed Therapies)
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