Autophagy Induction as a Host-Directed Therapeutic Strategy against <em>Mycobacterium tuberculosis</em> Infection
Tuberculosis (TB), a bacterialinfectious disease caused by <i>Mycobacterium tuberculosis</i> (<i>M.tb</i>), which causes significant mortality in humans worldwide. Current treatment regimen involve the administration of multiple antibiotics over the course of several months t...
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MDPI AG
2021-05-01
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| Series: | Medicina |
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| Online Access: | https://www.mdpi.com/1648-9144/57/6/522 |
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| author | Harresh Adikesavalu Radha Gopalaswamy Ashok Kumar Uma Devi Ranganathan Sivakumar Shanmugam |
| author_facet | Harresh Adikesavalu Radha Gopalaswamy Ashok Kumar Uma Devi Ranganathan Sivakumar Shanmugam |
| author_sort | Harresh Adikesavalu |
| collection | DOAJ |
| description | Tuberculosis (TB), a bacterialinfectious disease caused by <i>Mycobacterium tuberculosis</i> (<i>M.tb</i>), which causes significant mortality in humans worldwide. Current treatment regimen involve the administration of multiple antibiotics over the course of several months that contributes to patient non-compliance leading to relapse and the development of drug-resistant <i>M.tb</i> (MDR and XDR) strains. Together, these facts highlight the need for the development of shorter TB treatment regimens. Host-directed therapy (HDT) is a new and emerging concept that aims to augment host immune response using drugs/compounds with or without adjunct antibiotics against <i>M.tb</i> infection. Autophagy is a natural catabolic mechanism of the cell that involves delivering the cytosolic constituents to the lysosomes for degradation and recycling the components; thereby maintaining the cellular and energy homoeostasis of a cell. However, over the past decade, an improved understanding of the role of autophagy in immunity has led to autophagy activation by using drugs or agents. This autophagy manipulation may represent a promising host-directed therapeutic strategy for human TB. However, current clinical knowledge on implementing autophagy activation by drugs or agents, as a stand-alone HDT or as an adjunct with antibiotics to treat human TB is insufficient. In recent years, many reports on high-throughput drug screening and measurement of autophagic flux by fluorescence, high-content microscopy, flow cytometry, microplate reader and immunoblotting have been published for the discovery of drugs that modulate autophagy. In this review, we discuss the commonly used chemical screening approaches in mammalian cells for the discovery of autophagy activating drugs against <i>M.tb</i>infection. We also summarize the various autophagy-activating agents, both pre-clinical candidates and compounds approved for advanced clinical investigation during mycobacterial infection. Finally, we discuss the opportunities and challenges in using autophagy activation as HDT strategy to improve TB outcome and shorten treatment regimen. |
| first_indexed | 2024-03-10T11:08:02Z |
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| language | English |
| last_indexed | 2024-03-10T11:08:02Z |
| publishDate | 2021-05-01 |
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| series | Medicina |
| spelling | doaj.art-1de323ef3611417bbdcaeccafe7447092023-11-21T20:59:22ZengMDPI AGMedicina1010-660X1648-91442021-05-0157652210.3390/medicina57060522Autophagy Induction as a Host-Directed Therapeutic Strategy against <em>Mycobacterium tuberculosis</em> InfectionHarresh Adikesavalu0Radha Gopalaswamy1Ashok Kumar2Uma Devi Ranganathan3Sivakumar Shanmugam4Department of Bacteriology, ICMR-National Institute for Research in Tuberculosis, Chetpet, Chennai 600031, IndiaDepartment of Bacteriology, ICMR-National Institute for Research in Tuberculosis, Chetpet, Chennai 600031, IndiaDepartment of Bacteriology, ICMR-National Institute for Research in Tuberculosis, Chetpet, Chennai 600031, IndiaDepartment of Immunology, ICMR-National Institute for Research in Tuberculosis, Chetpet, Chennai 600031, IndiaDepartment of Bacteriology, ICMR-National Institute for Research in Tuberculosis, Chetpet, Chennai 600031, IndiaTuberculosis (TB), a bacterialinfectious disease caused by <i>Mycobacterium tuberculosis</i> (<i>M.tb</i>), which causes significant mortality in humans worldwide. Current treatment regimen involve the administration of multiple antibiotics over the course of several months that contributes to patient non-compliance leading to relapse and the development of drug-resistant <i>M.tb</i> (MDR and XDR) strains. Together, these facts highlight the need for the development of shorter TB treatment regimens. Host-directed therapy (HDT) is a new and emerging concept that aims to augment host immune response using drugs/compounds with or without adjunct antibiotics against <i>M.tb</i> infection. Autophagy is a natural catabolic mechanism of the cell that involves delivering the cytosolic constituents to the lysosomes for degradation and recycling the components; thereby maintaining the cellular and energy homoeostasis of a cell. However, over the past decade, an improved understanding of the role of autophagy in immunity has led to autophagy activation by using drugs or agents. This autophagy manipulation may represent a promising host-directed therapeutic strategy for human TB. However, current clinical knowledge on implementing autophagy activation by drugs or agents, as a stand-alone HDT or as an adjunct with antibiotics to treat human TB is insufficient. In recent years, many reports on high-throughput drug screening and measurement of autophagic flux by fluorescence, high-content microscopy, flow cytometry, microplate reader and immunoblotting have been published for the discovery of drugs that modulate autophagy. In this review, we discuss the commonly used chemical screening approaches in mammalian cells for the discovery of autophagy activating drugs against <i>M.tb</i>infection. We also summarize the various autophagy-activating agents, both pre-clinical candidates and compounds approved for advanced clinical investigation during mycobacterial infection. Finally, we discuss the opportunities and challenges in using autophagy activation as HDT strategy to improve TB outcome and shorten treatment regimen.https://www.mdpi.com/1648-9144/57/6/522<i>Mycobacterium tuberculosis</i>host-directed therapiesautophagyadjuvants |
| spellingShingle | Harresh Adikesavalu Radha Gopalaswamy Ashok Kumar Uma Devi Ranganathan Sivakumar Shanmugam Autophagy Induction as a Host-Directed Therapeutic Strategy against <em>Mycobacterium tuberculosis</em> Infection Medicina <i>Mycobacterium tuberculosis</i> host-directed therapies autophagy adjuvants |
| title | Autophagy Induction as a Host-Directed Therapeutic Strategy against <em>Mycobacterium tuberculosis</em> Infection |
| title_full | Autophagy Induction as a Host-Directed Therapeutic Strategy against <em>Mycobacterium tuberculosis</em> Infection |
| title_fullStr | Autophagy Induction as a Host-Directed Therapeutic Strategy against <em>Mycobacterium tuberculosis</em> Infection |
| title_full_unstemmed | Autophagy Induction as a Host-Directed Therapeutic Strategy against <em>Mycobacterium tuberculosis</em> Infection |
| title_short | Autophagy Induction as a Host-Directed Therapeutic Strategy against <em>Mycobacterium tuberculosis</em> Infection |
| title_sort | autophagy induction as a host directed therapeutic strategy against em mycobacterium tuberculosis em infection |
| topic | <i>Mycobacterium tuberculosis</i> host-directed therapies autophagy adjuvants |
| url | https://www.mdpi.com/1648-9144/57/6/522 |
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