The molecular basis of resistance to isoniazid, rifampin, and pyrazinamide in Mycobacterium tuberculosis

Abstract

Multidrug-resistant (MDR) strains of Mycobacterium tuberculosis have emerged worldwide. In many countries and regions, these resistant strains constitute a serious threat to the efficacy of tuberculosis control programs. An important element in gaining control of this epidemic is developing an understanding of the molecular basis of resistance to the most important antituberculosis drugs: isoniazid, rifampin, and pyrazinamide. On the basis of this information, more exacting laboratory testing, and ultimately more appropriate and timely treatment regimens, can be developed.

Figure 1

Previously demonstrated and proposed sites of action of isoniazid (INH), pyrazinamide (PZA), and rifampin (RMP) on the M tuberculosis cell. INH inhibits the synthesis of mycolic acids [19,20], PZA inhibits the synthesis of short-chain, fatty-acid precursors [32], and RMP inhibits transcription by binding to the β-subunit of RNA polymerase [28]. This figure is adapted in part from Parsons et al [40].