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  Frontline Science: Employing enzymatic treatment options for management of ocular biofilm-based infections

Kugadas, A., Geddes-McAlister, J., Guy, E., DiGiandomenico, A., Sykes, D. B., Mansour, M. K., et al. (2019). Frontline Science: Employing enzymatic treatment options for management of ocular biofilm-based infections. Journal of Leukocyte Biology, 105(6, SI), 1099-1110. doi:10.1002/JLB.4HI0918-364RR.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0004-8636-8 Version Permalink: http://hdl.handle.net/21.11116/0000-0004-8641-B
Genre: Journal Article

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 Creators:
Kugadas, Abirami1, Author
Geddes-McAlister, Jennifer2, Author              
Guy, Emilia1, Author
DiGiandomenico, Antonio1, Author
Sykes, David B.1, Author
Mansour, Michael K.1, Author
Mirchev, Rossen1, Author
Gadjeva, Mihaela1, Author
Affiliations:
1external, ou_persistent22              
2Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565159              

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Free keywords: PSEUDOMONAS-AERUGINOSA INVASION; CORNEAL EPITHELIAL-CELLS; MICROCOLONY FORMATION; ALPHA-MANNOSIDOSIS; PSL; KERATITIS; EXOPOLYSACCHARIDE; IDENTIFICATION; PHAGOCYTOSIS; MECHANISMSCell Biology; Hematology; Immunology; biofilms; innate immunity; neutrophils; P. aeruginosa;
 Abstract: Pseudomonas aeruginosa-induced corneal keratitis is a sight-threatening disease. The rise of antibiotic resistance among P. aeruginosa keratitis isolates makes treatment of this disease challenging, emphasizing the need for alternative therapeutic modalities. By comparing the responses to P. aeruginosa infection between an outbred mouse strain (Swiss Webster, SW) and a susceptible mouse strain (C57BL6/N), we found that the inherent neutrophil-killing abilities of these strains correlated with their susceptibility to infection. Namely, SW-derived neutrophils were significantly more efficient at killing P. aeruginosa in vitro than C57BL6/N-derived neutrophils. To interrogate whether the distinct neutrophil killing capacities were dependent on endogenous or exogenous factors, neutrophil progenitor cell lines were generated. The in vitro differentiated neutrophils from either SW or C57BL6/N progenitors retained the differential killing abilities, illustrating that endogenous factors conferred resistance. Consistently, quantitative LC-MS/MS analysis revealed strain-specific and infection-induced alterations of neutrophil proteomes. Among the distinctly elevated proteins in the SW-derived proteomes were alpha-mannosidases, potentially associated with protection. Inhibition of alpha-mannosidases reduced neutrophil bactericidal functions in vitro. Conversely, topical application of alpha-mannosidases reduced bacterial biofilms and burden of infected corneas. Cumulatively, these data suggest novel therapeutic approaches to control bacterial biofilm assembly and improve bacterial clearance via enzymatic treatments.

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Language(s): eng - English
 Dates: 2019-012019-06
 Publication Status: Published in print
 Pages: 12
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: ISI: 000474780600004
DOI: 10.1002/JLB.4HI0918-364RR
 Degree: -

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Title: Journal of Leukocyte Biology
  Other : J. Leukoc. Biol.
Source Genre: Journal
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Publ. Info: New York : Liss
Pages: - Volume / Issue: 105 (6, SI) Sequence Number: - Start / End Page: 1099 - 1110 Identifier: ISSN: 0741-5400
CoNE: https://pure.mpg.de/cone/journals/resource/954925539169