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Targeting Pseudomonas aeruginosa in the sputum of primary ciliary dyskinesia patients with a combinatorial strategy having antibacterial and anti-virulence potential

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Abstract
In primary ciliary dyskinesia (PCD) patients, Pseudomonas aeruginosa is a major opportunistic pathogen, frequently involved in chronic infections of the lower airways. Infections by this bacterial species correlates with a worsening clinical prognosis and recalcitrance to currently available therapeutics. The antimicrobial peptide, lin-SB056-1, in combination with the cation chelator ethylenediaminetetraacetic acid (EDTA), was previously demonstrated to be bactericidal against P. aeruginosa in an artificial sputum medium. The purpose of this study was to validate the anti-P. aeruginosa activity of such a combination in PCD sputum and to evaluate the in vitro anti-virulence effects of EDTA. In combination with EDTA, lin-SB056-1 was able to significantly reduce the load of endogenous P. aeruginosa ex vivo in the sputum of PCD patients. In addition, EDTA markedly reduced the production of relevant bacterial virulence factors (e.g., pyocyanin, proteases, LasA) in vitro by two representative mucoid strains of P. aeruginosa isolated from the sputum of PCD patients. These results indicate that the lin-SB056-1/EDTA combination may exert a dual antimicrobial and anti-virulence action against P. aeruginosa, suggesting a therapeutic potential against chronic airway infections sustained by this bacterium.
Keywords
antimicrobial peptide, EDTA, Pseudomonas aeruginosa, primary ciliary dyskinesia, virulence factor, anti-virulence, sputum, chronic infection, CALCIUM, EDTA, BIOFILM, LASA, INHIBITION, PYOVERDIN, ELASTASE, ALGINATE, EFFICACY, MUCUS

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MLA
Maisetta, Giuseppantonio, et al. “Targeting Pseudomonas Aeruginosa in the Sputum of Primary Ciliary Dyskinesia Patients with a Combinatorial Strategy Having Antibacterial and Anti-Virulence Potential.” INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, vol. 21, no. 1, 2020, doi:10.3390/ijms21010069.
APA
Maisetta, G., Grassi, L., Esin, S., Kaya, E., Morelli, A., Puppi, D., … Batoni, G. (2020). Targeting Pseudomonas aeruginosa in the sputum of primary ciliary dyskinesia patients with a combinatorial strategy having antibacterial and anti-virulence potential. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 21(1). https://doi.org/10.3390/ijms21010069
Chicago author-date
Maisetta, Giuseppantonio, Lucia Grassi, Semih Esin, Esingul Kaya, Andrea Morelli, Dario Puppi, Martina Piras, Federica Chiellini, Massimo Pifferi, and Giovanna Batoni. 2020. “Targeting Pseudomonas Aeruginosa in the Sputum of Primary Ciliary Dyskinesia Patients with a Combinatorial Strategy Having Antibacterial and Anti-Virulence Potential.” INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 21 (1). https://doi.org/10.3390/ijms21010069.
Chicago author-date (all authors)
Maisetta, Giuseppantonio, Lucia Grassi, Semih Esin, Esingul Kaya, Andrea Morelli, Dario Puppi, Martina Piras, Federica Chiellini, Massimo Pifferi, and Giovanna Batoni. 2020. “Targeting Pseudomonas Aeruginosa in the Sputum of Primary Ciliary Dyskinesia Patients with a Combinatorial Strategy Having Antibacterial and Anti-Virulence Potential.” INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 21 (1). doi:10.3390/ijms21010069.
Vancouver
1.
Maisetta G, Grassi L, Esin S, Kaya E, Morelli A, Puppi D, et al. Targeting Pseudomonas aeruginosa in the sputum of primary ciliary dyskinesia patients with a combinatorial strategy having antibacterial and anti-virulence potential. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. 2020;21(1).
IEEE
[1]
G. Maisetta et al., “Targeting Pseudomonas aeruginosa in the sputum of primary ciliary dyskinesia patients with a combinatorial strategy having antibacterial and anti-virulence potential,” INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, vol. 21, no. 1, 2020.
@article{8663111,
  abstract     = {{In primary ciliary dyskinesia (PCD) patients, Pseudomonas aeruginosa is a major opportunistic pathogen, frequently involved in chronic infections of the lower airways. Infections by this bacterial species correlates with a worsening clinical prognosis and recalcitrance to currently available therapeutics. The antimicrobial peptide, lin-SB056-1, in combination with the cation chelator ethylenediaminetetraacetic acid (EDTA), was previously demonstrated to be bactericidal against P. aeruginosa in an artificial sputum medium. The purpose of this study was to validate the anti-P. aeruginosa activity of such a combination in PCD sputum and to evaluate the in vitro anti-virulence effects of EDTA. In combination with EDTA, lin-SB056-1 was able to significantly reduce the load of endogenous P. aeruginosa ex vivo in the sputum of PCD patients. In addition, EDTA markedly reduced the production of relevant bacterial virulence factors (e.g., pyocyanin, proteases, LasA) in vitro by two representative mucoid strains of P. aeruginosa isolated from the sputum of PCD patients. These results indicate that the lin-SB056-1/EDTA combination may exert a dual antimicrobial and anti-virulence action against P. aeruginosa, suggesting a therapeutic potential against chronic airway infections sustained by this bacterium.}},
  articleno    = {{69}},
  author       = {{Maisetta, Giuseppantonio and Grassi, Lucia and Esin, Semih and Kaya, Esingul and Morelli, Andrea and Puppi, Dario and Piras, Martina and Chiellini, Federica and Pifferi, Massimo and Batoni, Giovanna}},
  issn         = {{1422-0067}},
  journal      = {{INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}},
  keywords     = {{antimicrobial peptide,EDTA,Pseudomonas aeruginosa,primary ciliary dyskinesia,virulence factor,anti-virulence,sputum,chronic infection,CALCIUM,EDTA,BIOFILM,LASA,INHIBITION,PYOVERDIN,ELASTASE,ALGINATE,EFFICACY,MUCUS}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{11}},
  title        = {{Targeting Pseudomonas aeruginosa in the sputum of primary ciliary dyskinesia patients with a combinatorial strategy having antibacterial and anti-virulence potential}},
  url          = {{http://doi.org/10.3390/ijms21010069}},
  volume       = {{21}},
  year         = {{2020}},
}

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