RESUMO
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 65°C. 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.
RESUMO
BACKGROUND: The study documented the emergence of new forms of resistant bacilli (totally drug-resistant [TDR] or super extensively drug-resistant [XDR] tuberculosis [TB] strains) among patients with multidrug-resistant TB (MDR-TB). METHODS: Susceptibility testing against first- and second-line drugs was performed on isolated Mycobacterium tuberculosis strains. Subsequently, the strains identified as XDR or TDR M tuberculosis were subjected to spoligotyping and variable numbers of tandem repeats (VNTR). RESULTS: Of 146 MDR-TB strains, 8 XDR isolates (5.4%) and 15 TDR isolates (10.3%) were identified. The remaining strains were either susceptible (67%) or had other resistant patterns (20%). Overall, the median of treatments and drugs previously received by MDR-TB patients was two courses of therapy of 15 months' duration with five drugs (isoniazid [INH], rifampicin [RF], streptomycin, ethambutol, and pyrazinamide). The median of in vitro drug resistance for all studied cases was INH and RF. The XDR or TDR strains were collected from both immigrants (Afghan, 30.4%; Azerbaijani, 8.6%; Iraqi, 4.3%) and Iranian (56.5%) MDR-TB cases. In such cases, the smear and cultures remained positive after 18 months of medium treatment with second-line drugs (ethionamide, para-aminosalicylic acid, cycloserine, ofloxacin, amikacin, and ciprofloxacin). Spoligotyping revealed Haarlem (39.1%), Beijing (21.7%), EAI (21.7%), and CAS (17.3%) superfamilies of M tuberculosis. These superfamilies had different VNTR profiles, which eliminated the recent transmission among MDR-TB cases. CONCLUSIONS: The isolation of TDR strains from MDR-TB patients from different regional countries is alarming and underlines the possible dissemination of such strains in Asian countries. Now the next question is how one should control and treat such cases.
