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The Repurposing of Anti-Psychotic Drugs, Quetiapine and Olanzapine, as Anti-Cryptococcus Drugs

The management of cryptococcal infections is often difficult. This can, in part, be attributed to the fungistatic nature of fluconazole, which may result in cells disseminating to give rise to pathogen-emergent psychosis following brain inflammation. This chance at treatment failure has necessitated...

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Autores principales: Ogundeji, Adepemi O., Pohl, Carolina H., Sebolai, Olihile M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5422476/
https://www.ncbi.nlm.nih.gov/pubmed/28536567
http://dx.doi.org/10.3389/fmicb.2017.00815
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author Ogundeji, Adepemi O.
Pohl, Carolina H.
Sebolai, Olihile M.
author_facet Ogundeji, Adepemi O.
Pohl, Carolina H.
Sebolai, Olihile M.
author_sort Ogundeji, Adepemi O.
collection PubMed
description The management of cryptococcal infections is often difficult. This can, in part, be attributed to the fungistatic nature of fluconazole, which may result in cells disseminating to give rise to pathogen-emergent psychosis following brain inflammation. This chance at treatment failure has necessitated the current study wherein the antimicrobial quality of anti-psychotic drugs viz. quetiapine and olanzapine, was assessed. The response of test strains toward quetiapine or olanzapine alone and in combined therapy with fluconazole or amphotericn B was measured. In addition, the mode of action of the two anti-psychotic drugs in killing cryptococcal cells was determined. At the end, the ability of these anti-psychotic drugs to chemo-sensitize macrophages was also examined. The assessed strains were shown to be susceptible to the two anti-psychotic drugs, which possibly killed them via altering their membrane function. Additionally, these anti-psychotic drugs acted in synergy with fluconazole and amphotericin B in controlling the growth of the test strains. Importantly, these drugs improved the phagocytic efficiency of macrophages and, at the same time, stimulated them to produce pro-inflammatory cytokines (interleukin 6 and interferon gamma), said to be critical in the clearance of cryptococcal cells. The minimum inhibition concentration of each anti-psychotic drugs was calculated to be within its respective recommended therapeutic range. This study's findings highlight the potential clinical application of quetiapine and olanzapine as alternative anti-Cryptococcus drugs, which can be used to manage the fungal burden (infection) as well as the associated symptom (psychosis).
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spelling pubmed-54224762017-05-23 The Repurposing of Anti-Psychotic Drugs, Quetiapine and Olanzapine, as Anti-Cryptococcus Drugs Ogundeji, Adepemi O. Pohl, Carolina H. Sebolai, Olihile M. Front Microbiol Microbiology The management of cryptococcal infections is often difficult. This can, in part, be attributed to the fungistatic nature of fluconazole, which may result in cells disseminating to give rise to pathogen-emergent psychosis following brain inflammation. This chance at treatment failure has necessitated the current study wherein the antimicrobial quality of anti-psychotic drugs viz. quetiapine and olanzapine, was assessed. The response of test strains toward quetiapine or olanzapine alone and in combined therapy with fluconazole or amphotericn B was measured. In addition, the mode of action of the two anti-psychotic drugs in killing cryptococcal cells was determined. At the end, the ability of these anti-psychotic drugs to chemo-sensitize macrophages was also examined. The assessed strains were shown to be susceptible to the two anti-psychotic drugs, which possibly killed them via altering their membrane function. Additionally, these anti-psychotic drugs acted in synergy with fluconazole and amphotericin B in controlling the growth of the test strains. Importantly, these drugs improved the phagocytic efficiency of macrophages and, at the same time, stimulated them to produce pro-inflammatory cytokines (interleukin 6 and interferon gamma), said to be critical in the clearance of cryptococcal cells. The minimum inhibition concentration of each anti-psychotic drugs was calculated to be within its respective recommended therapeutic range. This study's findings highlight the potential clinical application of quetiapine and olanzapine as alternative anti-Cryptococcus drugs, which can be used to manage the fungal burden (infection) as well as the associated symptom (psychosis). Frontiers Media S.A. 2017-05-09 /pmc/articles/PMC5422476/ /pubmed/28536567 http://dx.doi.org/10.3389/fmicb.2017.00815 Text en Copyright © 2017 Ogundeji, Pohl and Sebolai. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Ogundeji, Adepemi O.
Pohl, Carolina H.
Sebolai, Olihile M.
The Repurposing of Anti-Psychotic Drugs, Quetiapine and Olanzapine, as Anti-Cryptococcus Drugs
title The Repurposing of Anti-Psychotic Drugs, Quetiapine and Olanzapine, as Anti-Cryptococcus Drugs
title_full The Repurposing of Anti-Psychotic Drugs, Quetiapine and Olanzapine, as Anti-Cryptococcus Drugs
title_fullStr The Repurposing of Anti-Psychotic Drugs, Quetiapine and Olanzapine, as Anti-Cryptococcus Drugs
title_full_unstemmed The Repurposing of Anti-Psychotic Drugs, Quetiapine and Olanzapine, as Anti-Cryptococcus Drugs
title_short The Repurposing of Anti-Psychotic Drugs, Quetiapine and Olanzapine, as Anti-Cryptococcus Drugs
title_sort repurposing of anti-psychotic drugs, quetiapine and olanzapine, as anti-cryptococcus drugs
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5422476/
https://www.ncbi.nlm.nih.gov/pubmed/28536567
http://dx.doi.org/10.3389/fmicb.2017.00815
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