title: Membrane depolarization-triggered responsive diversification leads to antibiotic tolerance.
abstract: Bacterial populations are known to harbor a small fraction of so-called persister cells that have the remarkable ability to survive treatment with very high doses of antibiotics. Recent studies underscore the importance of persistence in chronic infections, yet the nature of persisters remains poorly understood. We recently showed that the universally conserved GTPase Obg modulates persistence via a (p)ppGpp-dependent mechanism that proceeds through expression of hokB. HokB is a membrane-bound toxin that causes the membrane potential to collapse. The resulting drop in cellular energy levels triggers a switch to the persistent state, yielding protection from antibiotic attack. Obg-mediated persistence is conserved in the human pathogenPseudomonas aeruginosa, making Obg a promising target for therapies directed against bacterial persistence.
authors.affiliation: Centre of Microbial and Plant Genetics, KU Leuven - University of Leuven, 3001 Leuven, Belgium.
authors.forename: Natalie
authors.initials: N
authors.lastname: Verstraeten
authors.affiliation: Centre of Microbial and Plant Genetics, KU Leuven - University of Leuven, 3001 Leuven, Belgium.
authors.forename: Wouter J
authors.initials: WJ
authors.lastname: Knapen
authors.affiliation: Centre of Microbial and Plant Genetics, KU Leuven - University of Leuven, 3001 Leuven, Belgium.
authors.forename: Maarten
authors.initials: M
authors.lastname: Fauvart
authors.affiliation: Centre of Microbial and Plant Genetics, KU Leuven - University of Leuven, 3001 Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Michiels
keywords: (p)ppGpp; CgtA; HokB; Obg; ObgE; YhbZ; antibiotic tolerance; membrane depolarization; persistence; responsive diversification; toxin antitoxin