Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 May;58(5):2979-81.
doi: 10.1128/AAC.00037-14. Epub 2014 Mar 3.

Cross-resistance between clofazimine and bedaquiline through upregulation of MmpL5 in Mycobacterium tuberculosis

Ruben C Hartkoorn  1 , Swapna Uplekar, Stewart T Cole
Affiliations

Cross-resistance between clofazimine and bedaquiline through upregulation of MmpL5 in Mycobacterium tuberculosis

Ruben C Hartkoorn et al. Antimicrob Agents Chemother. 2014 May.

Abstract

The antileprosy drug clofazimine is also of interest for the treatment of multidrug-resistant tuberculosis. To understand possible resistance mechanisms, clofazimine-resistant Mycobacterium tuberculosis mutants were isolated in vitro, and, unexpectedly, found to be cross-resistant to bedaquiline. Mutations in the transcriptional regulator Rv0678, with concomitant upregulation of the multisubstrate efflux pump, MmpL5, accounted for this cross-resistance. Mutation in Rv0678 should therefore be considered a confounding factor for the treatment of tuberculosis with clofazimine or bedaquiline.

PubMed Disclaimer

Figures

FIG 1
FIG 1
Drug susceptibility of MTB H37Rv (solid circles with solid lines) and H37RvCFZR1 (solid squares with dashed lines) to clofazimine (A), bedaquiline (B), econazole (C), and moxifloxicin (D) as measured by the resazurin reduction assay.
See this image and copyright information in PMC

References

    1. Van Deun A, Maug AK, Salim MA, Das PK, Sarker MR, Daru P, Rieder HL. 2010. Short, highly effective, and inexpensive standardized treatment of multidrug-resistant tuberculosis. Am. J. Respir. Crit. Care Med. 182:684–692. 10.1164/rccm.201001-0077OC - DOI - PubMed
    1. Yano T, Kassovska-Bratinova S, Teh JS, Winkler J, Sullivan K, Isaacs A, Schechter NM, Rubin H. 2011. Reduction of clofazimine by mycobacterial type 2 NADH:quinone oxidoreductase: a pathway for the generation of bactericidal levels of reactive oxygen species. J. Biol. Chem. 286:10276–10287. 10.1074/jbc.M110.200501 - DOI - PMC - PubMed
    1. Palomino JC, Martin A, Camacho M, Guerra H, Swings J, Portaels F. 2002. Resazurin microtiter assay plate: simple and inexpensive method for detection of drug resistance in Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 46:2720–2722. 10.1128/AAC.46.8.2720-2722.2002 - DOI - PMC - PubMed
    1. Hartkoorn RC, Sala C, Neres J, Pojer F, Magnet S, Mukherjee R, Uplekar S, Boy-Rottger S, Altmann KH, Cole ST. 2012. Towards a new tuberculosis drug: pyridomycin—nature's isoniazid. EMBO Mol. Med. 4:1032–1042. 10.1002/emmm.201201689 - DOI - PMC - PubMed
    1. Milano A, Pasca MR, Provvedi R, Lucarelli AP, Manina G, Ribeiro AL, Manganelli R, Riccardi G. 2009. Azole resistance in Mycobacterium tuberculosis is mediated by the MmpS5-MmpL5 efflux system. Tuberculosis (Edinb.) 89:84–90. 10.1016/j.tube.2008.08.003 - DOI - PubMed

Publication types

MeSH terms

LinkOut - more resources