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Involvement of Acquired Tobramycin Resistance in the Shift to the Viable but Non-Culturable State in Pseudomonas aeruginosa.
Mangiaterra, Gianmarco; Cedraro, Nicholas; Vaiasicca, Salvatore; Citterio, Barbara; Frangipani, Emanuela; Biavasco, Francesca; Vignaroli, Carla.
Afiliação
  • Mangiaterra G; Department of Biomolecular Sciences, University of Urbino Carlo Bo, Via S. Chiara 27, 61029 Urbino, Italy.
  • Cedraro N; Department of Life and Environmental Sciences, Polytechnic University of Marche, Via Brecce Bianche, 60131 Ancona, Italy.
  • Vaiasicca S; Department of Life and Environmental Sciences, Polytechnic University of Marche, Via Brecce Bianche, 60131 Ancona, Italy.
  • Citterio B; Department of Molecular and Clinical Sciences, Polytechnic University of Marche, Via Tronto 10/a, 60020 Ancona, Italy.
  • Frangipani E; Department of Biomolecular Sciences, University of Urbino Carlo Bo, Via S. Chiara 27, 61029 Urbino, Italy.
  • Biavasco F; Department of Biomolecular Sciences, University of Urbino Carlo Bo, Via S. Chiara 27, 61029 Urbino, Italy.
  • Vignaroli C; Department of Life and Environmental Sciences, Polytechnic University of Marche, Via Brecce Bianche, 60131 Ancona, Italy.
Int J Mol Sci ; 24(14)2023 Jul 18.
Article em En | MEDLINE | ID: mdl-37511375
Persistent and viable but non-culturable (VBNC) Pseudomonas aeruginosa cells are mainly responsible for the recurrence and non-responsiveness to antibiotics of cystic fibrosis (CF) lung infections. The sub-inhibitory antibiotic concentrations found in the CF lung in between successive therapeutic cycles can trigger the entry into the VBNC state, albeit with a strain-specific pattern. Here, we analyzed the VBNC cell induction in the biofilms of two CF P. aeruginosa isolates, exposed to starvation with/without antibiotics, and investigated the putative genetic determinants involved. Total viable bacterial cells were quantified by the validated ecfX-targeting qPCR protocol and the VBNC cells were estimated as the difference between qPCR and cultural counts. The isolates were both subjected to whole genome sequencing, with attention focused on their carriage of aminoglycoside resistance genes and on identifying mutated toxin-antitoxin and quorum sensing systems. The obtained results suggest the variable contribution of different antibiotic resistance mechanisms to VBNC cell abundance, identifying a major contribution from tobramycin efflux, mediated by MexXY efflux pump overexpression. The genome analysis evidenced putative mutation hotspots, which deserve further investigation. Therefore, drug efflux could represent a crucial mechanism through which the VBNC state is entered and a potential target for anti-persistence strategies.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Infecções por Pseudomonas / Fibrose Cística Tipo de estudo: Guideline / Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Infecções por Pseudomonas / Fibrose Cística Tipo de estudo: Guideline / Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article