title: Oligopolyphenylenevinylene-conjugated oligoelectrolyte membrane insertion molecules selectively disrupt cell envelopes of Gram-positive bacteria.
abstract: The modification of microbial membranes to achieve biotechnological strain improvement with exogenous small molecules, such as oligopolyphenylenevinylene-conjugated oligoelectrolyte (OPV-COE) membrane insertion molecules (MIMs), is an emerging biotechnological field. Little is known about the interactions of OPV-COEs with their target, the bacterial envelope. We studied the toxicity of three previously reported OPV-COEs with a selection of Gram-negative and Gram-positive organisms and demonstrated that Gram-positive bacteria are more sensitive to OPV-COEs than Gram-negative bacteria. Transmission electron microscopy demonstrated that these MIMs disrupt microbial membranes and that this occurred to a much greater degree in Gram-positive organisms. We used a number of mutants to probe the nature of MIM interactions with the microbial envelope but were unable to align the membrane perturbation effects of these compounds to previously reported membrane disruption mechanisms of, for example, cationic antimicrobial peptides. Instead, the data support the notion that OPV-COEs disrupt microbial membranes through a suspected interaction with diphosphatidylglycerol (DPG), a major component of Gram-positive membranes. The integrity of model membranes containing elevated amounts of DPG was disrupted to a greater extent by MIMs than those prepared from Escherichia coli total lipid extracts alone.
authors.affiliation: Singapore Centre on Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, Singapore, Singapore swuertz@ntu.edu.sg jhinks@ntu.edu.sg.
authors.forename: Jamie
authors.initials: J
authors.lastname: Hinks
authors.affiliation: Singapore Centre on Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, Singapore, Singapore.
authors.forename: Wee Han
authors.initials: WH
authors.lastname: Poh
authors.affiliation: Laboratory of Molecular RNA Virology and Antiviral Strategies, Department of Microbiology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore, Singapore.
authors.forename: Justin Jang Hann
authors.initials: JJ
authors.lastname: Chu
authors.affiliation: Singapore Centre on Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, Singapore, Singapore School of Materials Science and Engineering, Nanyang Technological University, Singapore, Singapore.
authors.forename: Joachim Say Chye
authors.initials: JS
authors.lastname: Loo
authors.affiliation: Department of Chemistry & Biochemistry and Materials, Center for Polymers and Organic Solids, University of California, Santa Barbara, California, USA.
authors.forename: Guillermo C
authors.initials: GC
authors.lastname: Bazan
authors.affiliation: Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas, USA.
authors.forename: Lynn E
authors.initials: LE
authors.lastname: Hancock
authors.affiliation: Singapore Centre on Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, Singapore, Singapore School of Civil and Environmental Engineering, Nanyang Technological University, Singapore, Singapore Department of Civil and Environmental Engineering, University of California, Davis, California, USA swuertz@ntu.edu.sg jhinks@ntu.edu.sg.
authors.forename: Stefan
authors.identifier: http://orcid.org/0000-0002-3415-6199
authors.initials: S
authors.lastname: Wuertz
mesh_terms: D002462:Cell Membrane / Q000187:drug effects*; D006090:Gram-Negative Bacteria / Q000166:cytology / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000166:cytology / Q000187:drug effects*; D046529:Microscopy, Electron, Transmission; D011145:Polyvinyls / Q000378:metabolism* / Q000633:toxicity*
chemical_list: D011145:Polyvinyls; C530822:oligo(p-phenylene vinylene)