The Synergistic Effects of the Glutathione Precursor, NAC and First-Line Antibiotics in the Granulomatous Response Against Mycobacterium tuberculosis
( ), the causative bacterial agent responsible for tuberculosis (TB) continues to afflict millions of people worldwide. Although the human immune system plays a critical role in containing infection, elimination proves immensely more challenging. Consequently, there has been a worldwide effort to er...
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| Published in | Frontiers in immunology Vol. 9; p. 2069 |
|---|---|
| Main Authors | , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Switzerland
Frontiers Media S.A
12.09.2018
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| Subjects | |
| Online Access | Get full text |
| ISSN | 1664-3224 1664-3224 |
| DOI | 10.3389/fimmu.2018.02069 |
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| Abstract | (
), the causative bacterial agent responsible for tuberculosis (TB) continues to afflict millions of people worldwide. Although the human immune system plays a critical role in containing
infection, elimination proves immensely more challenging. Consequently, there has been a worldwide effort to eradicate, and limit the spread of
through the conventional use of first-line antibiotics. Unfortunately, with the emergence of drug resistant and multi-drug resistant strains of
the archetypical antibiotics no longer provide the same ascendancy as they once did. Furthermore, when administered, these first-line antibiotics commonly present severe complications and side effects. The biological antioxidant glutathione (GSH) however, has been demonstrated to have a profound mycobactericidal effect with no reported adverse consequences. Therefore, we examined if N-Acetyl Cysteine (NAC), the molecular precursor to GSH, when supplemented in combination with suboptimal levels of standalone first-line antibiotics would be sufficient to completely clear
infection within
derived granulomas from healthy subjects and individuals with type 2 diabetes (T2DM). Our results revealed that by virtue of immune modulation, the addition of NAC to subprime levels of isoniazid (INH) and rifampicin (RIF) was indeed capable of inducing complete clearance of
among healthy individuals. |
|---|---|
| AbstractList | Mycobacterium tuberculosis (M. tb), the causative bacterial agent responsible for tuberculosis (TB) continues to afflict millions of people worldwide. Although the human immune system plays a critical role in containing M. tb infection, elimination proves immensely more challenging. Consequently, there has been a worldwide effort to eradicate, and limit the spread of M. tb through the conventional use of first-line antibiotics. Unfortunately, with the emergence of drug resistant and multi-drug resistant strains of M. tb the archetypical antibiotics no longer provide the same ascendancy as they once did. Furthermore, when administered, these first-line antibiotics commonly present severe complications and side effects. The biological antioxidant glutathione (GSH) however, has been demonstrated to have a profound mycobactericidal effect with no reported adverse consequences. Therefore, we examined if N-Acetyl Cysteine (NAC), the molecular precursor to GSH, when supplemented in combination with suboptimal levels of standalone first-line antibiotics would be sufficient to completely clear M. tb infection within in vitro derived granulomas from healthy subjects and individuals with type 2 diabetes (T2DM). Our results revealed that by virtue of immune modulation, the addition of NAC to subprime levels of isoniazid (INH) and rifampicin (RIF) was indeed capable of inducing complete clearance of M. tb among healthy individuals.Mycobacterium tuberculosis (M. tb), the causative bacterial agent responsible for tuberculosis (TB) continues to afflict millions of people worldwide. Although the human immune system plays a critical role in containing M. tb infection, elimination proves immensely more challenging. Consequently, there has been a worldwide effort to eradicate, and limit the spread of M. tb through the conventional use of first-line antibiotics. Unfortunately, with the emergence of drug resistant and multi-drug resistant strains of M. tb the archetypical antibiotics no longer provide the same ascendancy as they once did. Furthermore, when administered, these first-line antibiotics commonly present severe complications and side effects. The biological antioxidant glutathione (GSH) however, has been demonstrated to have a profound mycobactericidal effect with no reported adverse consequences. Therefore, we examined if N-Acetyl Cysteine (NAC), the molecular precursor to GSH, when supplemented in combination with suboptimal levels of standalone first-line antibiotics would be sufficient to completely clear M. tb infection within in vitro derived granulomas from healthy subjects and individuals with type 2 diabetes (T2DM). Our results revealed that by virtue of immune modulation, the addition of NAC to subprime levels of isoniazid (INH) and rifampicin (RIF) was indeed capable of inducing complete clearance of M. tb among healthy individuals. ( ), the causative bacterial agent responsible for tuberculosis (TB) continues to afflict millions of people worldwide. Although the human immune system plays a critical role in containing infection, elimination proves immensely more challenging. Consequently, there has been a worldwide effort to eradicate, and limit the spread of through the conventional use of first-line antibiotics. Unfortunately, with the emergence of drug resistant and multi-drug resistant strains of the archetypical antibiotics no longer provide the same ascendancy as they once did. Furthermore, when administered, these first-line antibiotics commonly present severe complications and side effects. The biological antioxidant glutathione (GSH) however, has been demonstrated to have a profound mycobactericidal effect with no reported adverse consequences. Therefore, we examined if N-Acetyl Cysteine (NAC), the molecular precursor to GSH, when supplemented in combination with suboptimal levels of standalone first-line antibiotics would be sufficient to completely clear infection within derived granulomas from healthy subjects and individuals with type 2 diabetes (T2DM). Our results revealed that by virtue of immune modulation, the addition of NAC to subprime levels of isoniazid (INH) and rifampicin (RIF) was indeed capable of inducing complete clearance of among healthy individuals. Mycobacterium tuberculosis (M. tb), the causative bacterial agent responsible for tuberculosis (TB) continues to afflict millions of people worldwide. Although the human immune system plays a critical role in containing M. tb infection, elimination proves immensely more challenging. Consequently, there has been a worldwide effort to eradicate, and limit the spread of M. tb through the conventional use of first-line antibiotics. Unfortunately, with the emergence of drug resistant and multi-drug resistant strains of M. tb the archetypical antibiotics no longer provide the same ascendancy as they once did. Furthermore, when administered, these first-line antibiotics commonly present severe complications and side effects. The biological antioxidant glutathione (GSH) however, has been demonstrated to have a profound mycobactericidal effect with no reported adverse consequences. Therefore, we examined if N-Acetyl Cysteine (NAC), the molecular precursor to GSH, when supplemented in combination with suboptimal levels of standalone first-line antibiotics would be sufficient to completely clear M. tb infection within in vitro derived granulomas from healthy subjects and individuals with type 2 diabetes (T2DM). Our results revealed that by virtue of immune modulation, the addition of NAC to subprime levels of isoniazid (INH) and rifampicin (RIF) was indeed capable of inducing complete clearance of M. tb among healthy individuals. |
| Author | Venketaraman, Vishwanath Fraix, Marcel Islamoglu, Hicret Prasad, Ramaa Cao, Ruoqiong Zhong, Li Teskey, Garrett Prasad, Chaya Sathananthan, Airani Subbian, Selvakumar Medina, Albert |
| AuthorAffiliation | 3 Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences , Pomona, CA , United States 4 Department of Biological Sciences, California State Polytechnic University , Pomona, CA , United States 1 College of life Sciences, Hebei University , Baoding , China 7 Public Health Research Institute (PHRI), New Jersey Medical School, Rutgers University , Newark, NJ , United States 5 Department of Internal Medicine, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences , Pomona, CA , United States 2 Graduate College of Biomedical Sciences, Western University of Health Sciences , Pomona, CA , United States 6 Department of Clinical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences , Pomona, CA , United States |
| AuthorAffiliation_xml | – name: 3 Department of Basic Medical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences , Pomona, CA , United States – name: 7 Public Health Research Institute (PHRI), New Jersey Medical School, Rutgers University , Newark, NJ , United States – name: 1 College of life Sciences, Hebei University , Baoding , China – name: 6 Department of Clinical Sciences, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences , Pomona, CA , United States – name: 4 Department of Biological Sciences, California State Polytechnic University , Pomona, CA , United States – name: 2 Graduate College of Biomedical Sciences, Western University of Health Sciences , Pomona, CA , United States – name: 5 Department of Internal Medicine, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences , Pomona, CA , United States |
| Author_xml | – sequence: 1 givenname: Garrett surname: Teskey fullname: Teskey, Garrett – sequence: 2 givenname: Ruoqiong surname: Cao fullname: Cao, Ruoqiong – sequence: 3 givenname: Hicret surname: Islamoglu fullname: Islamoglu, Hicret – sequence: 4 givenname: Albert surname: Medina fullname: Medina, Albert – sequence: 5 givenname: Chaya surname: Prasad fullname: Prasad, Chaya – sequence: 6 givenname: Ramaa surname: Prasad fullname: Prasad, Ramaa – sequence: 7 givenname: Airani surname: Sathananthan fullname: Sathananthan, Airani – sequence: 8 givenname: Marcel surname: Fraix fullname: Fraix, Marcel – sequence: 9 givenname: Selvakumar surname: Subbian fullname: Subbian, Selvakumar – sequence: 10 givenname: Li surname: Zhong fullname: Zhong, Li – sequence: 11 givenname: Vishwanath surname: Venketaraman fullname: Venketaraman, Vishwanath |
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| ContentType | Journal Article |
| Copyright | Copyright © 2018 Teskey, Cao, Islamoglu, Medina, Prasad, Prasad, Sathananthan, Fraix, Subbian, Zhong and Venketaraman. 2018 Teskey, Cao, Islamoglu, Medina, Prasad, Prasad, Sathananthan, Fraix, Subbian, Zhong and Venketaraman |
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| Keywords | cytokines type 2 diabetes Mycobacterium tuberculosis antitubercular antibiotics tuberculosis |
| Language | English |
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| Notes | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 This article was submitted to Microbial Immunology, a section of the journal Frontiers in Immunology These authors have contributed equally to this work Reviewed by: Amit Singhal, Singapore Immunology Network (A*STAR), Singapore; Reto Guler, University of Cape Town, South Africa Edited by: Robert Wilkinson, Francis Crick Institute, United Kingdom |
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