title: Antimicrobial treatment improves mycobacterial survival in nonpermissive growth conditions.
abstract: Antimicrobials targeting cell wall biosynthesis are generally considered inactive against nonreplicating bacteria. Paradoxically, we found that under nonpermissive growth conditions, exposure of Mycobacterium bovis BCG bacilli to such antimicrobials enhanced their survival. We identified a transcriptional regulator, RaaS (for regulator of antimicrobial-assisted survival), encoded by bcg1279 (rv1219c) as being responsible for the observed phenomenon. Induction of this transcriptional regulator resulted in reduced expression of specific ATP-dependent efflux pumps and promoted long-term survival of mycobacteria, while its deletion accelerated bacterial death under nonpermissive growth conditions in vitro and during macrophage or mouse infection. These findings have implications for the design of antimicrobial drug combination therapies for persistent infectious diseases, such as tuberculosis.
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom.
authors.forename: Obolbek
authors.initials: O
authors.lastname: Turapov
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Waddell
authors.forename: Bernard
authors.initials: B
authors.lastname: Burke
authors.forename: Sarah
authors.initials: S
authors.lastname: Glenn
authors.forename: Asel A
authors.initials: AA
authors.lastname: Sarybaeva
authors.forename: Griselda
authors.initials: G
authors.lastname: Tudo
authors.forename: Gilles
authors.initials: G
authors.lastname: Labesse
authors.forename: Danielle I
authors.initials: DI
authors.lastname: Young
authors.forename: Michael
authors.initials: M
authors.lastname: Young
authors.forename: Peter W
authors.initials: PW
authors.lastname: Andrew
authors.forename: Philip D
authors.initials: PD
authors.lastname: Butcher
authors.forename: Martin
authors.initials: M
authors.lastname: Cohen-Gonsaud
authors.forename: Galina V
authors.initials: GV
authors.lastname: Mukamolova
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D002460:Cell Line; D024202:Electrophoretic Mobility Shift Assay; D005454:Fluorescence Polarization; D006801:Humans; D051379:Mice; D009163:Mycobacterium bovis / Q000187:drug effects* / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000890:Anti-Infective Agents