title: Membrane-targeting AM-0016 kills mycobacterial persisters and shows low propensity for resistance development.
abstract: To test the hypothesis that targeting the cytoplasmic membrane may be an effective way to kill persister mycobacteria and delay the emergence of resistance.
  
  
  
  In vitro activity of AM-0016, a novel xanthone-based antibacterial, was assessed against growing and persister tubercle bacilli. Resistance mutation frequencies were determined. Biochemical membrane and electron microscopic analyses were carried out.
  
  
  
  AM-0016 rapidly sterilized growing tubercle bacillus cultures and displayed strong bactericidal activity against persister bacteria. Spontaneous resistance mutation frequency was lower than 10(-8). Exposure to AM-0016 resulted in rapid collapse of the membrane potential. Imaging revealed deformation of the cell envelope.
  
  
  
  Targeting the cytoplasmic membrane may be an attractive approach to eliminate persister mycobacteria and slow down the emergence of genetic drug resistance.
authors.affiliation: Department of Microbiology & Immunology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Singapore 117545.
authors.forename: Devika
authors.initials: D
authors.lastname: Mukherjee
authors.affiliation: Singapore Eye Research Institute, The Academia, 20 College Road, Discovery Tower Level 6, Singapore 169856.
authors.forename: Hanxun
authors.initials: H
authors.lastname: Zou
authors.affiliation: Singapore Eye Research Institute, The Academia, 20 College Road, Discovery Tower Level 6, Singapore 169856.|SRP Neuroscience & Behavioural Disorders, Duke-NUS Graduate Medical School, Singapore 169857.
authors.forename: Shouping
authors.initials: S
authors.lastname: Liu
authors.affiliation: Singapore Eye Research Institute, The Academia, 20 College Road, Discovery Tower Level 6, Singapore 169856.|SRP Neuroscience & Behavioural Disorders, Duke-NUS Graduate Medical School, Singapore 169857.|Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119074.
authors.forename: Roger
authors.initials: R
authors.lastname: Beuerman
authors.affiliation: Department of Microbiology & Immunology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Singapore 117545.
authors.forename: Thomas
authors.initials: T
authors.lastname: Dick
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects*; D024881:Drug Resistance, Bacterial; D008564:Membrane Potentials / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000254:growth & development*; D044004:Xanthones / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D044004:Xanthones; C009689:xanthone
keywords: drug resistance; drug tolerance; tuberculosis