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

Publication Type:

Journal Article

Authors:

Adams, Kristin N; Verma, Amit Kumar; Gopalaswamy, Radha; Adikesavalu, Harresh; Singhal, Dinesh Kumar; Tripathy, Srikanth; Ranganathan, Uma Devi; Sherman, David R; Urdahl, Kevin B; Ramakrishnan, Lalita; Hernandez, Rafael E

Source:

The Journal of Infectious Diseases, Volume 219, p.1554-1558 (2019)

URL:

https://doi.org/10.1093/infdis/jiy710

Abstract:

<p>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.</p>