title: Function of the cytochrome bc1-aa3 branch of the respiratory network in mycobacteria and network adaptation occurring in response to its disruption.
abstract: The aerobic electron transport chain in Mycobacterium smegmatis can terminate in one of three possible terminal oxidase complexes. The structure and function of the electron transport pathway leading from the menaquinol-menaquinone pool to the cytochrome bc1 complex and terminating in the aa3-type cytochrome c oxidase was characterized. M. smegmatis strains with mutations in the bc1 complex and in subunit II of cyctochome c oxidase were found to be profoundly growth impaired, confirming the importance of this respiratory pathway for mycobacterial growth under aerobic conditions. Disruption of this pathway resulted in an adaptation of the respiratory network that is characterized by a marked up-regulation of cydAB, which encodes the bioenergetically less efficient and microaerobically induced cytochrome bd-type menaquinol oxidase that is required for the growth of M. smegmatis under O2-limiting conditions. Further insights into the adaptation of this organism to rerouting of the electron flux through the branch terminating in the bd-type oxidase were revealed by expression profiling of the bc1-deficient mutant strain using a partial-genome microarray of M. smegmatis that is enriched in essential genes. Although the expression profile was indicative of an increase in the reduced state of the respiratory chain, blockage of the bc1-aa3 pathway did not induce the sentinel genes of M. smegmatis that are induced by oxygen starvation and are regulated by the DosR two-component regulator.
authors.affiliation: MRC/NHLS/WITS Molecular Mycobacteriology Research Unit, DST/NRF/ Centre of Excellence in Biomedical TB Research, School of Pathology, National Health Laboratory Service, Johannesburg, South Africa.
authors.forename: Limenako G
authors.initials: LG
authors.lastname: Matsoso
authors.forename: Bavesh D
authors.initials: BD
authors.lastname: Kana
authors.forename: Paul K
authors.initials: PK
authors.lastname: Crellin
authors.forename: David J
authors.initials: DJ
authors.lastname: Lea-Smith
authors.forename: Assunta
authors.initials: A
authors.lastname: Pelosi
authors.forename: David
authors.initials: D
authors.lastname: Powell
authors.forename: Stephanie S
authors.initials: SS
authors.lastname: Dawes
authors.forename: Harvey
authors.initials: H
authors.lastname: Rubin
authors.forename: Ross L
authors.initials: RL
authors.lastname: Coppel
authors.forename: Valerie
authors.initials: V
authors.lastname: Mizrahi
mesh_terms: D004579:Electron Transport; D045222:Electron Transport Chain Complex Proteins; D014450:Electron Transport Complex III / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D003576:Electron Transport Complex IV / Q000737:chemistry / Q000378:metabolism; D020102:Mycobacterium smegmatis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption
chemical_list: D045222:Electron Transport Chain Complex Proteins; D003576:Electron Transport Complex IV; D014450:Electron Transport Complex III; D010100:Oxygen