IJCEM Copyright © 2008-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Int J Clin Exp Med 2010;4(3):193-199

Original Article
Sequential adaptation in latent tuberculosis bacilli: observation by atomic force
microscopy (AFM)

Ali Akbar Velayati, Parissa Farnia, Mohammad  Reza Masjedi, Gennady Konstantinovich Zhavnerko, Muayad Aghali Merza, Jalladein
Ghanavei,  Payam Tabarsi, Poopak Farnia,  Nikolai Nikolaevich Poleschuyk,  George Ignatyev

Mycobacteriology Research  Centre, National Research Institute of Tuberculosis and Lung Disease (NRITLD), WHO & UNION
Collaborating Centre for TB & Lung Diseases, Shahid  Beheshti University (Medical Campus), Darabad, Tehran,19556, P.O:
19575/154, Iran; The Republican Research and Practical Centre for Epidemiology & and Microbiology, Filimonova 23,Minsk, Belarus;
Institute for Chemistry of New Materials, Belarus National Academy of Sciences, F.Skoriny 36,220141 Minsk, Belarus; Experimental &
animal research Laboratory, NRITLD, Shahid Beheshti University (Medical Campus), Darabad, Tehran, 19556, P.O: 19575/154, Iran.

Received June 27, 2011; accepted August 31, 2011; Epub September 15, 2011; published September 30, 2011

Abstract: Mycobacterium tuberculosis (MTB) can persist within the human host for years without causing disease, in a syndrome
known as latent tuberculosis. The mechanisms by which M. tuberculosis establishes a latent metabolic state is unknown, but it is
hypothesized that reduced oxygen tension may trigger the bacillus to enter a state of latency. Therefore, we are studying anaerobic
culture of M. tuberculosis (H37RV) as a model of latency. For the first time, the sequential adaptation of latent bacilli (every 90 days for
48 months) viewed under Atomic Force Microscopy (AFM). Two types of adaptation were observed and are described here. First, cells
are undergoing temporary adaptation (from 1 to 18 months of latency) that includes; thickening of cell wall (20.5±1.8 nm versus 15.2±1.
8 nm, P<0.05), formation of ovoid cells by “folding phenomena“(65-70%), size reduction (0.8± 0.1 µm versus 2.5±0.5 µm), and budding
type of cell division (20-25%).A second feature include changes that accompany development of specialized cells i.e., production of
spore like cells (0.5 ± 0.2 µm) and their progeny (filterable non -acid fast forms; 150 to 300 µm in size). Although, these cells were not
real spore because they fail to form a heat resistant colony forming units, after incubation for 35-40 min at 650C. The filterable non-acid
fast forms of bacilli are metabolically active and increased their number by symmetrical type of cell-division. Therefore, survival
strategies that developed by M. tuberculosis under oxygen limited condition are linked to its shape, size and conspicuous loss of acid
fastness.   (IJCEM1106004).

Key words: Latent TB bacilli, oxygen depletion, Atomic Force Microscopy

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Address all correspondence to:
Dr. P.Farnia,
Mycobacteriology Research Centre
NRITLD/UNION & WHO Collaborative Centre for TB & Lung Diseases
Shahid Beheshti University (Medical Campus), Tehran, 19556,
P.O:19575/154, IRAN,
Fax No: 00982120109505,
E-mail: pfarnia@hotmail.com