Metformin Increases Cell Viability and Regulates Pro-Inflammatory Response to Mtb
Nikita Naicker,1 Hylton Rodel,2 Rubeshan Perumal,1 Yashica Ganga,2 Mallory Bernstein,2 Ntombi Benede,2 Salim Abdool Karim,1,3 Nesri Padayacthi,1,3 Alex Sigal,2,4,5 Kogieleum Naidoo1,3 1Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa; 2Africa Health Research...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2023-06-01
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| Series: | Infection and Drug Resistance |
| Subjects: | |
| Online Access: | https://www.dovepress.com/metformin-increases-cell-viability-and-regulates-pro-inflammatory-resp-peer-reviewed-fulltext-article-IDR |
| _version_ | 1797789421626458112 |
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| author | Naicker N Rodel H Perumal R Ganga Y Bernstein M Benede N Abdool Karim S Padayacthi N Sigal A Naidoo K |
| author_facet | Naicker N Rodel H Perumal R Ganga Y Bernstein M Benede N Abdool Karim S Padayacthi N Sigal A Naidoo K |
| author_sort | Naicker N |
| collection | DOAJ |
| description | Nikita Naicker,1 Hylton Rodel,2 Rubeshan Perumal,1 Yashica Ganga,2 Mallory Bernstein,2 Ntombi Benede,2 Salim Abdool Karim,1,3 Nesri Padayacthi,1,3 Alex Sigal,2,4,5 Kogieleum Naidoo1,3 1Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa; 2Africa Health Research Institute, Durban, South Africa; 3MRC-CAPRISA HIV-TB Pathogenesis and Treatment Research Unit, Doris Duke Medical Research Institute; University of KwaZulu-Natal, Durban, South Africa; 4School of Laboratory Medicine and Medical Sciences; University of KwaZulu-Natal, Durban, South Africa; 5Max Planck Institute for Infection Biology, Berlin, GermanyCorrespondence: Nikita Naicker, Doris Duke Medical Research Institute, 2nd Floor, 719 Umbilo Road, Durban, 4041, South Africa, Tel +27843011636, Email nikita.naicker@caprisa.orgIntroduction: Current TB treatment regimens are pathogen-directed and can be severely compromised by the development of drug resistance. Metformin has been proposed as an adjunctive therapy for TB, however relatively little is known about how metformin modulates the cellular interaction between Mtb and macrophages. We aimed to characterize how metformin modulates Mtb growth within macrophages.Methods: We utilized live cell tracking through time-lapse microscopy to better understand the biological effect of metformin in response to Mtb infection. Furthermore, the potent first-line anti-TB drug, isoniazid, was used as a comparator and as a companion drug.Results: Metformin caused a 14.2-fold decrease in Mtb growth compared to the untreated control. Metformin combined with isoniazid controlled Mtb growth is slightly better than isoniazid alone. Metformin demonstrated the ability to regulate the cytokine and chemokine response over a 72 hour period, better than isoniazid only.Conclusion: We provide novel evidence that metformin controls mycobacterial growth by increasing host cell viability, and a direct and independent pro-inflammatory response to Mtb. Understanding the impact of metformin on Mtb growth within macrophages will advance our current knowledge on metformin as an adjunctive therapy, providing a new host-directed approach to TB treatment.Keywords: metformin, tuberculosis, host-directed therapy, INH, adjunctive therapy |
| first_indexed | 2024-03-13T01:50:24Z |
| format | Article |
| id | doaj.art-4770ee5401d54f8ab174780bc46926ae |
| institution | Directory Open Access Journal |
| issn | 1178-6973 |
| language | English |
| last_indexed | 2024-03-13T01:50:24Z |
| publishDate | 2023-06-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Infection and Drug Resistance |
| spelling | doaj.art-4770ee5401d54f8ab174780bc46926ae2023-07-02T19:49:16ZengDove Medical PressInfection and Drug Resistance1178-69732023-06-01Volume 163629363884280Metformin Increases Cell Viability and Regulates Pro-Inflammatory Response to MtbNaicker NRodel HPerumal RGanga YBernstein MBenede NAbdool Karim SPadayacthi NSigal ANaidoo KNikita Naicker,1 Hylton Rodel,2 Rubeshan Perumal,1 Yashica Ganga,2 Mallory Bernstein,2 Ntombi Benede,2 Salim Abdool Karim,1,3 Nesri Padayacthi,1,3 Alex Sigal,2,4,5 Kogieleum Naidoo1,3 1Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa; 2Africa Health Research Institute, Durban, South Africa; 3MRC-CAPRISA HIV-TB Pathogenesis and Treatment Research Unit, Doris Duke Medical Research Institute; University of KwaZulu-Natal, Durban, South Africa; 4School of Laboratory Medicine and Medical Sciences; University of KwaZulu-Natal, Durban, South Africa; 5Max Planck Institute for Infection Biology, Berlin, GermanyCorrespondence: Nikita Naicker, Doris Duke Medical Research Institute, 2nd Floor, 719 Umbilo Road, Durban, 4041, South Africa, Tel +27843011636, Email nikita.naicker@caprisa.orgIntroduction: Current TB treatment regimens are pathogen-directed and can be severely compromised by the development of drug resistance. Metformin has been proposed as an adjunctive therapy for TB, however relatively little is known about how metformin modulates the cellular interaction between Mtb and macrophages. We aimed to characterize how metformin modulates Mtb growth within macrophages.Methods: We utilized live cell tracking through time-lapse microscopy to better understand the biological effect of metformin in response to Mtb infection. Furthermore, the potent first-line anti-TB drug, isoniazid, was used as a comparator and as a companion drug.Results: Metformin caused a 14.2-fold decrease in Mtb growth compared to the untreated control. Metformin combined with isoniazid controlled Mtb growth is slightly better than isoniazid alone. Metformin demonstrated the ability to regulate the cytokine and chemokine response over a 72 hour period, better than isoniazid only.Conclusion: We provide novel evidence that metformin controls mycobacterial growth by increasing host cell viability, and a direct and independent pro-inflammatory response to Mtb. Understanding the impact of metformin on Mtb growth within macrophages will advance our current knowledge on metformin as an adjunctive therapy, providing a new host-directed approach to TB treatment.Keywords: metformin, tuberculosis, host-directed therapy, INH, adjunctive therapyhttps://www.dovepress.com/metformin-increases-cell-viability-and-regulates-pro-inflammatory-resp-peer-reviewed-fulltext-article-IDRmetformintuberculosishost-directed therapyinhadjunctive therapy |
| spellingShingle | Naicker N Rodel H Perumal R Ganga Y Bernstein M Benede N Abdool Karim S Padayacthi N Sigal A Naidoo K Metformin Increases Cell Viability and Regulates Pro-Inflammatory Response to Mtb Infection and Drug Resistance metformin tuberculosis host-directed therapy inh adjunctive therapy |
| title | Metformin Increases Cell Viability and Regulates Pro-Inflammatory Response to Mtb |
| title_full | Metformin Increases Cell Viability and Regulates Pro-Inflammatory Response to Mtb |
| title_fullStr | Metformin Increases Cell Viability and Regulates Pro-Inflammatory Response to Mtb |
| title_full_unstemmed | Metformin Increases Cell Viability and Regulates Pro-Inflammatory Response to Mtb |
| title_short | Metformin Increases Cell Viability and Regulates Pro-Inflammatory Response to Mtb |
| title_sort | metformin increases cell viability and regulates pro inflammatory response to mtb |
| topic | metformin tuberculosis host-directed therapy inh adjunctive therapy |
| url | https://www.dovepress.com/metformin-increases-cell-viability-and-regulates-pro-inflammatory-resp-peer-reviewed-fulltext-article-IDR |
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