Gene expression analysis of Mycobacterium tuberculosis high-persister (hip) mutants.

Bacterial persister cells are phenotypic variants of regular cells that are tolerant to antibiotics. High-persister (hip) mutants of Mycobacterium tuberculosis produce 10- to 1,000-fold more persister cells than the wild type strain when challenged with various antibiotics. Comparison of gene expression pattern of the hip mutants may provide clues as to the genetic mechanisms underlying persister formation. Transcriptome analysis will provide information on what differentiates M. tuberculosis hip strains from regular strains, which will be useful in the development of anti-persister therapy for persister cell eradication. Twelve independent M. tuberculosis hip mutants and the wild type strain were grown to stationary phase in duplicate. To avoid analyzing the drug effect, total RNA was extracted from the cultures prior to the addition of antibiotic for hybridization to Affymetrix microarrays. Data analysis was performed by comparing the hip mutants to the wild type control.