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

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 virulenc...

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Veröffentlicht in:Microbial pathogenesis Jg. 77; S. 36 - 41
Hauptverfasser: Marguerettaz, Mélanie, Dieppois, Guennaëlle, Que, Yok Ai, Ducret, Véréna, Zuchuat, Sandrine, Perron, Karl
Format: Journal Article
Sprache:Englisch
Veröffentlicht: England Elsevier Ltd 01.12.2014
Schlagworte:
Anti-Bacterial Agents - pharmacology
antibiotic resistance
Biofilm
Biofilms - growth & development
Carbapenem
carbapenems
Carbapenems - pharmacology
Cystic fibrosis
dietary mineral supplements
Drug Resistance, Bacterial
Humans
lungs
Membrane Transport Proteins - metabolism
metal tolerance
mortality
patients
porins
Pseudomonas aeruginosa
Pseudomonas aeruginosa - drug effects
Pseudomonas aeruginosa - enzymology
Pseudomonas aeruginosa - growth & development
Pseudomonas aeruginosa - physiology
Signal Transduction
Sputum
Sputum - chemistry
Sputum - microbiology
Virulence
Zinc
Zinc - analysis
Zinc - metabolism
Carbapenem
Virulence
Sputum
Biofilm
Pseudomonas aeruginosa
Cystic fibrosis
Zinc
ISSN:0882-4010, 1096-1208, 1096-1208
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Zusammenfassung: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. •Sputum of cystic fibrosis patients contains excess of zinc.•We use an artificial sputum medium to observe the effect of zinc on Pseudomonas aeruginosa.•Zinc exposure activates the pathogenicity, carbapenem resistance and biofilm formation of P. aeruginosa.•Zinc represses the expression of the OprD porin via a yet unknown mechanism.•Our data show that zinc levels in sputum of cystic fibrosis patients might aggravate P. aeruginosa infection.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0882-4010
1096-1208
1096-1208
DOI:10.1016/j.micpath.2014.10.011