The 1, 2-ethylenediamine SQ109 protects against tuberculosis by promoting M1 macrophage polarization through the p38 MAPK pathway
© 2022. The Author(s)..
Directly Observed Treatment Short-course (DOTs), is an effective and widely recommended treatment for tuberculosis (TB). The antibiotics used in DOTs, are immunotoxic and impair effector T cells, increasing the risk of re-infections and reactivation. Multiple reports suggest that addition of immune-modulators along with antibiotics improves the effectiveness of TB treatment. Therefore, drugs with both antimicrobial and immunomodulatory properties are desirable. N1-(Adamantan-2-yl)-N2-[(2E)-3,7-dimethylocta-2,6-dien-1-yl]ethane-1,2-diamine (SQ109) is an asymmetric diamine derivative of adamantane, that targets Mycobacterial membrane protein Large 3 (MmpL3). SQ109 dissipates the transmembrane electrochemical proton-gradient necessary for cell-wall biosynthesis and bacterial activity. Here, we examined the effects of SQ109 on host-immune responses using a murine TB model. Our results suggest the pro-inflammatory nature of SQ109, which instigates M1-macrophage polarization and induces protective pro-inflammatory cytokines through the p38-MAPK pathway. SQ109 also promotes Th1 and Th17-immune responses that inhibit the bacillary burden in a murine model of TB. These findings put forth SQ109 as a potential-adjunct to TB antibiotic therapy.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:5 |
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| Enthalten in: |
Communications biology - 5(2022), 1 vom: 28. Juli, Seite 759 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Singh, Mona [VerfasserIn] |
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| Links: |
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| Themen: |
60V9STC53F |
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| Anmerkungen: |
Date Completed 01.08.2022 Date Revised 22.08.2022 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s42003-022-03693-2 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM344224163 |
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| 520 | |a Directly Observed Treatment Short-course (DOTs), is an effective and widely recommended treatment for tuberculosis (TB). The antibiotics used in DOTs, are immunotoxic and impair effector T cells, increasing the risk of re-infections and reactivation. Multiple reports suggest that addition of immune-modulators along with antibiotics improves the effectiveness of TB treatment. Therefore, drugs with both antimicrobial and immunomodulatory properties are desirable. N1-(Adamantan-2-yl)-N2-[(2E)-3,7-dimethylocta-2,6-dien-1-yl]ethane-1,2-diamine (SQ109) is an asymmetric diamine derivative of adamantane, that targets Mycobacterial membrane protein Large 3 (MmpL3). SQ109 dissipates the transmembrane electrochemical proton-gradient necessary for cell-wall biosynthesis and bacterial activity. Here, we examined the effects of SQ109 on host-immune responses using a murine TB model. Our results suggest the pro-inflammatory nature of SQ109, which instigates M1-macrophage polarization and induces protective pro-inflammatory cytokines through the p38-MAPK pathway. SQ109 also promotes Th1 and Th17-immune responses that inhibit the bacillary burden in a murine model of TB. These findings put forth SQ109 as a potential-adjunct to TB antibiotic therapy | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Antitubercular Agents |2 NLM | |
| 650 | 7 | |a Ethylenediamines |2 NLM | |
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| 700 | 1 | |a Singh, Baldeep |e verfasserin |4 aut | |
| 700 | 1 | |a Jain, Preeti |e verfasserin |4 aut | |
| 700 | 1 | |a Kumari, Anjna |e verfasserin |4 aut | |
| 700 | 1 | |a Pahuja, Isha |e verfasserin |4 aut | |
| 700 | 1 | |a Chaturvedi, Shivam |e verfasserin |4 aut | |
| 700 | 1 | |a Prasad, Durbaka Vijay Raghava |e verfasserin |4 aut | |
| 700 | 1 | |a Dwivedi, Ved Prakash |e verfasserin |4 aut | |
| 700 | 1 | |a Das, Gobardhan |e verfasserin |4 aut | |
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