Dataset Information

Are there enzymatic treatment options for ocular biofilm-based infections?

ABSTRACT: Pseudomonas aeruginosa-induced corneal keratitis is a sight-threatening disease. The elevated rise of antibiotic resistance among the Pseudomonas keratitis isolates makes treatment of this disease challenging, justifying the need for alternative therapeutic modalities or treatment strategies that can reinforce antibiotic activities. By comparing the responses of P. aeruginosa infection on an outbred strain of mice (SW) to a susceptible strain of mice (C57BL6/N), we found that the neutrophil killing abilities of these strains segregate with their susceptibilities to infection. Namely, SW-derived neutrophils were significantly more efficient at killing P. aeruginosa in vitro than C57BL6/N-derived neutrophils. Quantitative LC-MS/MS analysis revealed significant differences in proteins with enzymatic activities such as alpha mannosidases. Given that during infection, P. aeruginosa forms mannose-rich biofilms at the ocular surface in the susceptible strain of mice, we compared the therapeutic potency of MoAb, recognizing the mannose-rich extracellular polysaccharide, psl, to that of alpha mannosidase. The topical application of alpha mannosidase reduced in vitro-formed biofilms by P. aeruginosa and consistently reduced the bacterial burden of the infected corneas. Cumulatively, these data illustrate that topical application of enzymes can control bacterial biofilm assembly and improve bacterial clearance.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Neutrophil

DISEASE(S): Keratitis

SUBMITTER: Jennifer Geddes-McAlister

LAB HEAD: Jennifer Geddes-McAlister

PROVIDER: PXD009767 | Pride | 2019-05-15

REPOSITORIES: Pride

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Publications

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

Kugadas Abirami A Geddes-McAlister Jennifer J Guy Emilia E DiGiandomenico Antonio A Sykes David B DB Mansour Michael K MK Mirchev Rossen R Gadjeva Mihaela M

Journal of leukocyte biology 20190128 6

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 th ...[more]

PMID: 30690787

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Project description:The aim of this experiment was to explore transcriptomic changes in the gills of Altantic salmon (Salmo salar) following a model lab based parr smolt transformation from fresh water (FW) to salt water (SW). The process of smoltification (migration from FW to SW) is stimulated by long day photoperiod, which acts on the tissue-specific levels of active thyroid hormone (triiodothyronine, T3) through the expression of thyroid hormone type 2 deiodinase (dio2), responsible for conversion of inactive thyroxine (T4) to T3. To gain insight into the functional significance of dio2 induction, we performed a SW-challenge experiment in which we inhibited dio2 activity by addition of iopanoic acid (IOP) to the SW. We also assessed the ability of co-treatment with T3 to override IOP effects. Juvenile fish maintained in FW were subjected to a standard smolt photoperiod regime known to stimulate smoltification, after which they were randomly allocated to one of the four treatments: SW, SW+IOP, SW+IOP+T3 and FW as a control. Fish (n = 8-10 per treatment) were exposed to these conditions for 6 h and then sacrificed to obtain gill tissue for microarray analysis, carried out using a custom-designed Agilent oligonucleotide microarray platform Salar_2 (one glass slide with 4 x 44K arrays, Agilent design ID: 025520, array design A-MEXP-2065), developed and validated for Atlantic salmon (for details, see specific protocols) . In total, 36 hybridisations were performed on gills from individual fish, with 8-10 replicate fish per treatment. We identified 1939 genes whose expression was significantly increased or decreased by transfer from FW to SW. For a subset of 259 genes, this SW response was abolished if IOP was added to the SW, but maintained if T3 was also present during IOP treatment. This group of genes constitutes a candidate list, for which SW-inducibility appears to be dependent on locally mediated changes in gill T3 availability. The results of this experiment have been submitted for publication in Current Biology and are currently under review.

Dataset Information

Are there enzymatic treatment options for ocular biofilm-based infections?

Publications

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

Similar Datasets

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