Efflux pump gene expression study using RNA-seq in multidrug-resistant TB

Author:

Lee J. J.1,Kang H. Y.2,Lee W-I.3,Cho S. Y.2,Kim Y. J.2,Lee H. J.4

Affiliation:

1. Department of Laboratory Medicine, Graduate School, Kyung Hee University, Seoul, Korea, Department of Laboratory Medicine, Kyung Hee University Hospital, Kyung Hee University School of Medicine, Seoul, Korea

2. Department of Laboratory Medicine, Kyung Hee University Hospital, Kyung Hee University School of Medicine, Seoul, Korea

3. Department of Laboratory Medicine, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Korea

4. Korean National Tuberculosis Association, Seoul, Korea

Abstract

BACKGROUND: The mechanism underlying kanamycin (KM) resistance in Mycobacterium tuberculosis is not well understood, although efflux pump proteins are thought to play a role. This study used RNA-seq data to investigate changes in the expression levels of efflux pump genes following exposure to KM.METHODS: RNA expression of efflux pump and regulatory genes following exposure to different concentrations of KM (minimum inhibitory concentration MIC 25 and MIC50) in rrs wild-type strain and rrs A1401G mutated strain were compared with the control group.RESULTS: The selected strains had differential RNA expression patterns. Among the 71 putative efflux pump and regulatory genes, 46 had significant fold changes, and 12 genes (Rv0842, Rv1146, Rv1258c, Rv1473, Rv1686c, Rv1687c, Rv1877, Rv2038c, Rv3065, Rv3197a, Rv3728 and Rv3789) that were overexpressed following exposure to KM were thought to contribute to drug resistance. Rv3197A (whiB7) showed a distinct fold change based on the concentration of KM.CONCLUSION: The significant changes in the expression of the efflux pump and regulatory genes following exposure to KM may provide insights into the identification of a new resistance mechanism.

Publisher

International Union Against Tuberculosis and Lung Disease

Subject

Infectious Diseases,Pulmonary and Respiratory Medicine

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