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

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, Hasia Kaidar Shwartz, Zeev Dveyrin, Efrat Rorman, Israel Nissan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageAmerican English
Article number1292665
JournalFrontiers in Medicine
Volume10
DOIs
StatePublished - 2023

Bibliographical note

Publisher Copyright:
Copyright © 2023 Rubinstein, Makhon, Losev, Valenci, Gatt, Margalit, Fass, Kutikov, Murik, Zeevi, Savyon, Tau, Kaidar Shwartz, Dveyrin, Rorman and Nissan.

Keywords

  • HspX
  • Mycobacterium tuberculosis (MTB)
  • acquired immunodeficiency syndrome (AIDS)
  • dormancy
  • human immunodeficiency virus (HIV)
  • in vivo evolution
  • multidrug-resistant tuberculosis (MDR-TB)
  • whole genome sequencing (WGS)

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