title: Antimicrobial activity of clofazimine is not dependent on mycobacterial C-type phospholipases.
abstract: We have used a phospholipase C (PLC)-deletion mutant (plcABC) of the H37Rv strain of Mycobacterium tuberculosis (MTB), as well as a plcA-insertion mutant of Mycobacterium smegmatis, to investigate the possible involvement of PLCs in clofazimine-mediated inhibition of mycobacterial K(+) transport and growth. Inactivation of the PLCs of MTB and insertion of the plcA gene into M. smegmatis resulted in a substantial reduction and increase in hydrolysis of phosphatidylcholine (PC), respectively. However, both the mutant and wild-type strains of MTB and M. smegmatis were equally sensitive to the inhibitory effects of clofazimine on K(+) uptake and growth. These observations demonstrate that the PLCs of MTB are not involved in the antimicrobial activity of clofazimine.
authors.affiliation: Tuberculosis Research Lead Programme, Medical Research Council, Pretoria, South Africa.
authors.forename: M C
authors.initials: MC
authors.lastname: Bopape
authors.forename: H C
authors.initials: HC
authors.lastname: Steel
authors.forename: R
authors.initials: R
authors.lastname: Cockeran
authors.forename: N M
authors.initials: NM
authors.lastname: Matlola
authors.forename: P B
authors.initials: PB
authors.lastname: Fourie
authors.forename: R
authors.initials: R
authors.lastname: Anderson
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000378:metabolism; D002991:Clofazimine / Q000494:pharmacology*; D003512:Cyclohexanones / Q000494:pharmacology; D017353:Gene Deletion; D006868:Hydrolysis; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors; D020102:Mycobacterium smegmatis / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics; D012414:Rubidium Radioisotopes; D010738:Type C Phospholipases / Q000235:genetics / Q000502:physiology*
chemical_list: D000890:Anti-Infective Agents; D003512:Cyclohexanones; D012414:Rubidium Radioisotopes; D016718:Arachidonic Acid; C036535:1,6-bis(cyclohexyloximinocarbonyl)hexane; D002991:Clofazimine; D008071:Lipoprotein Lipase; D010738:Type C Phospholipases