Prolonged survival of a patient with active MDR-TB HIV co-morbidity: insights from a Mycobacterium tuberculosis strain with a unique genomic deletion.

Autor:	Rubinstein M; National Public Health Laboratory, Public Health Directorate, Ministry of Health, Tel Aviv, Israel., Makhon A; National Public Health Laboratory, Public Health Directorate, Ministry of Health, Tel Aviv, Israel., Losev Y; National Public Health Laboratory, Public Health Directorate, Ministry of Health, Tel Aviv, Israel., Valenci GZ; National Public Health Laboratory, Public Health Directorate, Ministry of Health, Tel Aviv, Israel., Gatt YE; Department of Microbiology and Molecular Genetics, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel., Margalit H; Department of Microbiology and Molecular Genetics, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel., Fass E; National Public Health Laboratory, Public Health Directorate, Ministry of Health, Tel Aviv, Israel., Kutikov I; National Public Health Laboratory, Public Health Directorate, Ministry of Health, Tel Aviv, Israel., Murik O; Translational Genomics Laboratory, Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem, Israel., Zeevi DA; Translational Genomics Laboratory, Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem, Israel., Savyon M; Tel Aviv District Health Office, Ministry of Health, Tel Aviv, Israel., Tau L; Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.; Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel., Kaidar Shwartz H; National Public Health Laboratory, Public Health Directorate, Ministry of Health, Tel Aviv, Israel., Dveyrin Z; National Public Health Laboratory, Public Health Directorate, Ministry of Health, Tel Aviv, Israel., Rorman E; National Public Health Laboratory, Public Health Directorate, Ministry of Health, Tel Aviv, Israel., Nissan I; National Public Health Laboratory, Public Health Directorate, Ministry of Health, Tel Aviv, Israel.
Jazyk:	angličtina
Zdroj:	Frontiers in medicine [Front Med (Lausanne)] 2023 Nov 06; Vol. 10, pp. 1292665. Date of Electronic Publication: 2023 Nov 06 (Print Publication: 2023).
DOI:	10.3389/fmed.2023.1292665
Abstrakt:	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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Rubinstein, Makhon, Losev, Valenci, Gatt, Margalit, Fass, Kutikov, Murik, Zeevi, Savyon, Tau, Kaidar Shwartz, Dveyrin, Rorman and Nissan.)
Databáze:	MEDLINE
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