Cell Envelope Thickening: A Mechanism of Drug Resistance in Mycobacterium Tuberculosis

Abstract

Emergence of multi-drug-resistant (MDR) strains of Mycobacterium tuberculosis (Mtb) is recognized as an alarming threat to public health and it limits the number of compounds available for treatment of global tuberculosis (TB) epidemic. MDR is defined as resistance to at least two first line drugs, e.g. Rifampicin and Isoniazid, used commonly for the treatment of this disease. Multi-drug resistance may be due to presence of a thick, hydrophobic, impermeable, and waxy cell envelope (cell wall and cell membrane combined together). The present study investigated the cell envelope thickness in Rifampicin and Isoniazid resistant and sensitive Mtb isolates by transmission electron microscopy (TEM). Electron microscopic examination exhibited evident differences in cell envelope thickness between the sensitive (approx. 24 - 27 nm) and resistant (approx. 34 - 42 nm) Mtb isolates. Thus, this study demonstrated that thickening of cell envelope in resistant isolates might be one of the primary defense mechanisms adopted by Mtb against antibacterial drugs and the observed resistance towards Rifampicin and Isoniazid, the major first line drugs used against TB, might be attributed to this enhanced cell envelope thickness in drug resistant strains.