Action of clofazimine on Mycobacterium avium and Mycobacterium intracellulare

Clofazimine is a member of the phenazine pigment family which has been successfully used in chemotherapy against a variety of mycobacteria including M. avium. The presence of clofazimine in growth medium resulted in higher carotenoid pigmentation in M. avium cells. Carotenoid pigments have been shown to quench superoxide radicals supporting the hypothesis that pigmentation possibly protected cells against superoxide. Clofazimine caused the generation of superoxide radicals in M. intracellulare strain LR163 represented by cyanide-resistant oxygen consumption. The amount of oxygen consumed was dependant upon the clofazimine concentration. This supports the hypothesis that clofazimine is antibiotic via its ability to generate toxic oxygen metabolites. Higher catalase activity was found in extracts of cells grown in the presence of a low concentration of clofazimine. At a higher concentration, the amount of catalase and superoxide dismutase activities were lower than the basal level. This finding did not agree with the hypothesis. At this point the reason for the drop in the activities (i.e. lower than basal level) is not known. Clofazimine was mildly synergistic with rifampicin. This result supports hypothesis that the defense mechanism of M. intracellulare to clofazimine was enzymatic. Clofazimine-resistant derivatives of M. intracellulare strain LR163 have been isolated. Their characterization will provide a direct approach towards determining the mode of action of clofazimine in cells.

Name thesis:degree_name

Master of Science

Level thesis:degree_level

masters

Discipline thesis:degree_discipline

Microbiology

Department dc:contributor.department

Microbiology

Grantor dc:publisher

Virginia Tech

Year dc:date.issued

1990

Author dc:creator

• Warek, Ujwala

Statement dc:rights

• In Copyright

Licence dc:rights.uri

• http://rightsstatements.org/vocab/InC/1.0/

Language dc:language.iso

en

Dc Identifier Other

etd-03042009-040856

OAI identifier oai:identifier

oai:vtechworks.lib.vt.edu:10919/41419