Sputum containing zinc enhances carbapenem resistance, biofilm formation and virulence of Pseudomonas aeruginosa

Article Article scientifique Article Sputum containing zinc enhances carbapenem resistance, biofilm formation and virulence of Pseudomonas aeruginosa eng 2014 author Marguerettaz Mélanie 765692 author Dieppois Guennaelle 592919 author Que Yok Ai author Ducret Verena 596806 author Zuchuat Sandrine 636232 author Perron Karl 45679 36-41 10.1016/j.micpath.2014.10.011 25448466 0882-4010 Pseudomonas aeruginosa chronic lung infections are the leading cause of mortality in cystic fibrosis patients, a serious problem which is notably due to the numerous P. aeruginosa virulence factors, to its ability to form biofilms and to resist the effects of most antibiotics. Production of virulence factors and biofilm formation by P. aeruginosa is highly coordinated through complex regulatory systems. We recently found that CzcRS, the zinc and cadmium-specific two-component system is not only involved in metal resistance, but also in virulence and carbapenem antibiotic resistance in P. aeruginosa. Interestingly, zinc has been shown to be enriched in the lung secretions of cystic fibrosis patients. In this study, we investigated whether zinc might favor P. aeruginosa pathogenicity using an artificial sputum medium to mimic the cystic fibrosis lung environment. Our results show that zinc supplementation triggers a dual P. aeruginosa response: (i) it exacerbates pathogenicity by a CzcRS two-component system-dependent mechanism and (ii) it stimulates biofilm formation by a CzcRS-independent mechanism. Furthermore, P. aeruginosa cells embedded in these biofilms exhibited increased resistance to carbapenems. We identified a novel Zn-sensitive regulatory circuit controlling the expression of the OprD porin and modifying the carbapenem resistance profile. Altogether our data demonstrated that zinc levels in the sputum of cystic fibrosis patients might aggravate P. aeruginosa infection. Targeting zinc levels in sputum would be a valuable strategy to curb the increasing burden of P. aeruginosa infections in cystic fibrosis patients. Anti-Bacterial Agents/pharmacology Biofilms/growth & development Carbapenems/pharmacology Drug Resistance, Bacterial Humans Membrane Transport Proteins/metabolism Pseudomonas aeruginosa/drug effects/enzymology/growth & development/physiology Signal Transduction Sputum/chemistry/microbiology Virulence Zinc/analysis/metabolism Dewey 580 45 Département des sciences végétales 163 false Microbial pathogenesis 77 b553624b-0355-4738-8fb0-bc01540f5744 Article (Published version) Restricted Marguerettaz-et-al-2014.pdf 637362 application/pdf restrictedAccess Faculté des sciences / Section de biologie / Département des sciences végétales

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Sputum containing zinc enhances carbapenem resistance, biofilm formation and virulence of Pseudomonas aeruginosa	Microbial pathogenesis			2014	499	0

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Marguerettaz, Mélanie