New insight into extremely drug-resistant tuberculosis: using atomic force microscopy

Abstract

To the Editors: We have recently documented the emergence of new forms of resistant tuberculosis (TB) bacilli (totally drug resistant (TDR)-TB or extremely drug-resistant (XXDR)-TB strains) among multidrug-resistant (MDR)-TB patients 1. XXDR-TB defines any case of TB with resistance to all first- and second-line anti-TB drugs whose smears and cultures remain positive despite prolonged therapy 1–3. At the cellular level of XXDR-TB strains, adaptation was observed and evaluated using transmission electron microscopy (TEM) 4, 5. In the exponential phase, three different cell populations were clearly distinguished: one displayed an ordinary pattern (70–80%), one exhibited a round or oval shape (15–20%), and the third displayed an extraordinarily thick cell wall (21–26 nm) with features similar to stationary or anaerobic dormant bacilli (5–7%) 3, 4. These adapted forms were detected in all XXDR-TB isolates, irrespective of their super families or genotype patterns. We tried to evaluate the different cell population of XXDR-TB strains in comparison to susceptible cells using atomic force microcsopy (AFM). To achieve this goal, we included sputum and culture positive specimens of the same patients in our study. AFM images were recorded in contact mode using an optical lever microscope equipped with a liquid cell (Nanoscope IV Multimode AFM; Veeco Metrology Group, Santa Barbara, …