Expression of a novel mycobacterial phosphodiesterase successfully lowers cAMP levels resulting in reduced tolerance to cell wall–targeting antimicrobials
M. Thomson, Yi Liu, Kanokkan Nunta, Ashleigh Cheyne, Nadia Fernandes, Richard Williams, Acely Garza-Garcı́a, Gerald Larrouy‐Maumus
Abstract
155, we demonstrate that recombinant expression of Rv1339 reduced cAMP levels threefold and resulted in altered gene expression, impaired bioenergetics, and a disruption in peptidoglycan biosynthesis leading to decreased tolerance to antimicrobials that target cell wall synthesis such as ethambutol, D-cycloserine, and vancomycin. This work increases our understanding of the role of cAMP in mycobacterial antimicrobial tolerance, and our observations suggest that nucleotide signaling may represent a new target for the development of antimicrobial therapies.
Topics & Concepts
AntimicrobialMycobacterium smegmatisMultidrug toleranceBiologyMicrobiologyPhosphodiesteraseAntibiotic resistanceCyclic nucleotideCell biologyBiochemistryAntibioticsBacteriaBiofilmEnzymeGeneMycobacterium tuberculosisGeneticsNucleotideMedicineTuberculosisPathologyAntibiotic Resistance in BacteriaTuberculosis Research and EpidemiologyMycobacterium research and diagnosis