Prolonged survival of a patient with active MDR-TB HIV co-morbidity: insights from a Mycobacterium tuberculosis strain with a unique genomic deletion
Coinfection of HIV and multidrug-resistant tuberculosis (MDR-TB) presents significant challenges in terms of the treatment and prognosis of tuberculosis, leading to complexities in managing the disease and impacting the overall outcome for TB patients. This study presents a remarkable case of a pati...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-11-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2023.1292665/full |
| _version_ | 1797635680101203968 |
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| author | Mor Rubinstein Andrei Makhon Yelena Losev Gal Zizelski Valenci Yair E. Gatt Hanah Margalit Ephraim Fass Ina Kutikov Omer Murik David A. Zeevi Michal Savyon Luba Tau Luba Tau Hasia Kaidar Shwartz Zeev Dveyrin Efrat Rorman Israel Nissan |
| author_facet | Mor Rubinstein Andrei Makhon Yelena Losev Gal Zizelski Valenci Yair E. Gatt Hanah Margalit Ephraim Fass Ina Kutikov Omer Murik David A. Zeevi Michal Savyon Luba Tau Luba Tau Hasia Kaidar Shwartz Zeev Dveyrin Efrat Rorman Israel Nissan |
| author_sort | Mor Rubinstein |
| collection | DOAJ |
| description | Coinfection of HIV and multidrug-resistant tuberculosis (MDR-TB) presents significant challenges in terms of the treatment and prognosis of tuberculosis, leading to complexities in managing the disease and impacting the overall outcome for TB patients. This study presents a remarkable case of a patient with MDR-TB and HIV coinfection who survived for over 8 years, despite poor treatment adherence and comorbidities. Whole genome sequencing (WGS) of the infecting Mycobacterium tuberculosis (Mtb) strain revealed a unique genomic deletion, spanning 18 genes, including key genes involved in hypoxia response, intracellular survival, immunodominant antigens, and dormancy. This deletion, that we have called “Del-X,” potentially exerts a profound influence on the bacterial physiology and its virulence. Only few similar deletions were detected in other non-related Mtb genomes worldwide. In vivo evolution analysis identified drug resistance and metabolic adaptation mutations and their temporal dynamics during the patient’s treatment course. |
| first_indexed | 2024-03-11T12:24:47Z |
| format | Article |
| id | doaj.art-796d15d07df242cb80b578e11bdb0b03 |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-03-11T12:24:47Z |
| publishDate | 2023-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-796d15d07df242cb80b578e11bdb0b032023-11-06T13:07:52ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2023-11-011010.3389/fmed.2023.12926651292665Prolonged survival of a patient with active MDR-TB HIV co-morbidity: insights from a Mycobacterium tuberculosis strain with a unique genomic deletionMor Rubinstein0Andrei Makhon1Yelena Losev2Gal Zizelski Valenci3Yair E. Gatt4Hanah Margalit5Ephraim Fass6Ina Kutikov7Omer Murik8David A. Zeevi9Michal Savyon10Luba Tau11Luba Tau12Hasia Kaidar Shwartz13Zeev Dveyrin14Efrat Rorman15Israel Nissan16National Public Health Laboratory, Public Health Directorate, Ministry of Health, Tel Aviv, IsraelNational Public Health Laboratory, Public Health Directorate, Ministry of Health, Tel Aviv, IsraelNational Public Health Laboratory, Public Health Directorate, Ministry of Health, Tel Aviv, IsraelNational Public Health Laboratory, Public Health Directorate, Ministry of Health, Tel Aviv, IsraelDepartment of Microbiology and Molecular Genetics, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, IsraelDepartment of Microbiology and Molecular Genetics, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, IsraelNational Public Health Laboratory, Public Health Directorate, Ministry of Health, Tel Aviv, IsraelNational Public Health Laboratory, Public Health Directorate, Ministry of Health, Tel Aviv, IsraelTranslational Genomics Laboratory, Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem, IsraelTranslational Genomics Laboratory, Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem, IsraelTel Aviv District Health Office, Ministry of Health, Tel Aviv, IsraelTel Aviv Sourasky Medical Center, Tel Aviv, IsraelFaculty of Medicine, Tel Aviv University, Tel Aviv, IsraelNational Public Health Laboratory, Public Health Directorate, Ministry of Health, Tel Aviv, IsraelNational Public Health Laboratory, Public Health Directorate, Ministry of Health, Tel Aviv, IsraelNational Public Health Laboratory, Public Health Directorate, Ministry of Health, Tel Aviv, IsraelNational Public Health Laboratory, Public Health Directorate, Ministry of Health, Tel Aviv, IsraelCoinfection of HIV and multidrug-resistant tuberculosis (MDR-TB) presents significant challenges in terms of the treatment and prognosis of tuberculosis, leading to complexities in managing the disease and impacting the overall outcome for TB patients. This study presents a remarkable case of a patient with MDR-TB and HIV coinfection who survived for over 8 years, despite poor treatment adherence and comorbidities. Whole genome sequencing (WGS) of the infecting Mycobacterium tuberculosis (Mtb) strain revealed a unique genomic deletion, spanning 18 genes, including key genes involved in hypoxia response, intracellular survival, immunodominant antigens, and dormancy. This deletion, that we have called “Del-X,” potentially exerts a profound influence on the bacterial physiology and its virulence. Only few similar deletions were detected in other non-related Mtb genomes worldwide. In vivo evolution analysis identified drug resistance and metabolic adaptation mutations and their temporal dynamics during the patient’s treatment course.https://www.frontiersin.org/articles/10.3389/fmed.2023.1292665/fullMycobacterium tuberculosis (MTB)acquired immunodeficiency syndrome (AIDS)human immunodeficiency virus (HIV)multidrug-resistant tuberculosis (MDR-TB)HspXwhole genome sequencing (WGS) |
| spellingShingle | Mor Rubinstein Andrei Makhon Yelena Losev Gal Zizelski Valenci Yair E. Gatt Hanah Margalit Ephraim Fass Ina Kutikov Omer Murik David A. Zeevi Michal Savyon Luba Tau Luba Tau Hasia Kaidar Shwartz Zeev Dveyrin Efrat Rorman Israel Nissan Prolonged survival of a patient with active MDR-TB HIV co-morbidity: insights from a Mycobacterium tuberculosis strain with a unique genomic deletion Frontiers in Medicine Mycobacterium tuberculosis (MTB) acquired immunodeficiency syndrome (AIDS) human immunodeficiency virus (HIV) multidrug-resistant tuberculosis (MDR-TB) HspX whole genome sequencing (WGS) |
| title | Prolonged survival of a patient with active MDR-TB HIV co-morbidity: insights from a Mycobacterium tuberculosis strain with a unique genomic deletion |
| title_full | Prolonged survival of a patient with active MDR-TB HIV co-morbidity: insights from a Mycobacterium tuberculosis strain with a unique genomic deletion |
| title_fullStr | Prolonged survival of a patient with active MDR-TB HIV co-morbidity: insights from a Mycobacterium tuberculosis strain with a unique genomic deletion |
| title_full_unstemmed | Prolonged survival of a patient with active MDR-TB HIV co-morbidity: insights from a Mycobacterium tuberculosis strain with a unique genomic deletion |
| title_short | Prolonged survival of a patient with active MDR-TB HIV co-morbidity: insights from a Mycobacterium tuberculosis strain with a unique genomic deletion |
| title_sort | prolonged survival of a patient with active mdr tb hiv co morbidity insights from a mycobacterium tuberculosis strain with a unique genomic deletion |
| topic | Mycobacterium tuberculosis (MTB) acquired immunodeficiency syndrome (AIDS) human immunodeficiency virus (HIV) multidrug-resistant tuberculosis (MDR-TB) HspX whole genome sequencing (WGS) |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2023.1292665/full |
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