AUTHOR=Rubinstein Mor , Makhon Andrei , Losev Yelena , Valenci Gal Zizelski , Gatt Yair E. , Margalit Hanah , Fass Ephraim , Kutikov Ina , Murik Omer , Zeevi David A. , Savyon Michal , Tau Luba , Kaidar Shwartz Hasia , Dveyrin Zeev , Rorman Efrat , Nissan Israel 

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

JOURNAL=Frontiers in Medicine

VOLUME=10

YEAR=2023

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2023.1292665

DOI=10.3389/fmed.2023.1292665

ISSN=2296-858X

ABSTRACT=<p>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 <italic>Mycobacterium tuberculosis</italic> (<italic>Mtb</italic>) 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 <italic>Mtb</italic> genomes worldwide. <italic>In vivo</italic> evolution analysis identified drug resistance and metabolic adaptation mutations and their temporal dynamics during the patient’s treatment course.</p>