Morphological variability and cell-wall deficiency in Mycobacterium tuberculosis 'heteroresistant' strains.
METHODS
Sofia State Hospital for Tuberculosis Treatment, Bulgaria.


OBJECTIVE
To investigate the morphology of two 'heteroresistant' clinical isolates and one non-heteroresistant isolate, all isolated from newly diagnosed tuberculosis (TB) patients, as well as the reference strain H37Rv. Heteroresistant isolates contained clonally-related sensitive and drug-resistant organisms which could subsequently be separated using drug-containing primary cultures and had been isolated from patients originally diagnosed with susceptible TB by the 1% proportion method. Mycobacterial cultures were evaluated by transmission electron microscopy after 25 days of cultivation in Dubos broth.


RESULTS
In contrast to H37Rv and the non-heteroresistant isolate, the bacterial populations in both heteroresistant isolates demonstrated distinct pleomorphic variability and coexistence of both classical and cell-wall deficient forms. Electron micrographs of mutants resistant to streptomycin and isoniazid showed predominance of atypical granular L-forms, which formed L-type colonies on Dubos agar.


CONCLUSIONS
The L-form transformation processes, observed both in clinical heteroresistant isolates containing mixed populations of Mycobacterium tuberculosis organisms with different resistance gene genotypes and in the isolated resistant (mutant) clones, indicate a possible link between resistance and cell-wall deficient L-phase states and suggest one of the possible mechanisms by which resistant mutants are able to survive in vivo.
Michailova
L
L
Institute of Microbiology, Bulgarian Academy of Sciences, Sofia, Bulgaria.
Kussovski
V
V
Radoucheva
T
T
Jordanova
M
M
Berger
W
W
Rinder
H
H
Markova
N
N
D000995:Antitubercular Agents / Q000494:pharmacology*; D002473:Cell Wall / Q000473:pathology*; D024881:Drug Resistance, Bacterial / Q000235:genetics; D005838:Genotype; D009169:Mycobacterium tuberculosis / Q000166:cytology* / Q000235:genetics / Q000472:pathogenicity*; D010641:Phenotype
D000995:Antitubercular Agents