title: Morphological variability and cell-wall deficiency in Mycobacterium tuberculosis 'heteroresistant' strains.
abstract: 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.
authors.affiliation: Institute of Microbiology, Bulgarian Academy of Sciences, Sofia, Bulgaria.
authors.forename: L
authors.initials: L
authors.lastname: Michailova
authors.forename: V
authors.initials: V
authors.lastname: Kussovski
authors.forename: T
authors.initials: T
authors.lastname: Radoucheva
authors.forename: M
authors.initials: M
authors.lastname: Jordanova
authors.forename: W
authors.initials: W
authors.lastname: Berger
authors.forename: H
authors.initials: H
authors.lastname: Rinder
authors.forename: N
authors.initials: N
authors.lastname: Markova
mesh_terms: 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
chemical_list: D000995:Antitubercular Agents