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Diverse Clinical Isolates of Mycobacterium tuberculosis Develop Macrophage-Induced Rifampin Tolerance.


ABSTRACT: The Mycobacterium tuberculosis lineage 4 strains CDC1551 and H37Rv develop tolerance to multiple antibiotics upon macrophage residence. To determine whether macrophage-induced tolerance is a general feature of clinical M. tuberculosis isolates, we assessed macrophage-induced drug tolerance in strains from lineages 1-3, representing the other predominant M. tuberculosis strains responsible for tuberculosis globally. All 3 lineages developed isoniazid tolerance. While lineage 1, 3, and 4 strains developed rifampin tolerance, lineage 2 Beijing strains did not. Their failure to develop tolerance may be explained by their harboring of a loss-of-function mutation in the Rv1258c efflux pump that is linked to macrophage-induced rifampicin tolerance.

SUBMITTER: Adams KN 

PROVIDER: S-EPMC6473171 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Diverse Clinical Isolates of Mycobacterium tuberculosis Develop Macrophage-Induced Rifampin Tolerance.

Adams Kristin N KN   Verma Amit Kumar AK   Gopalaswamy Radha R   Adikesavalu Harresh H   Singhal Dinesh Kumar DK   Tripathy Srikanth S   Ranganathan Uma Devi UD   Sherman David R DR   Urdahl Kevin B KB   Ramakrishnan Lalita L   Hernandez Rafael E RE  

The Journal of infectious diseases 20190401 10


The Mycobacterium tuberculosis lineage 4 strains CDC1551 and H37Rv develop tolerance to multiple antibiotics upon macrophage residence. To determine whether macrophage-induced tolerance is a general feature of clinical M. tuberculosis isolates, we assessed macrophage-induced drug tolerance in strains from lineages 1-3, representing the other predominant M. tuberculosis strains responsible for tuberculosis globally. All 3 lineages developed isoniazid tolerance. While lineage 1, 3, and 4 strains d  ...[more]

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