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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Dataset's files

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			Action	DRS
	20171106_QX4_JeGe_SA_Pr5_C57_infect-1_171107165232.raw	Raw
	20171106_QX4_JeGe_SA_Pr5_C57_infect-2_171107193823.raw	Raw
	20171106_QX4_JeGe_SA_Pr5_C57_infect-3_171107222421.raw	Raw
	20171106_QX4_JeGe_SA_Pr5_C57_uninfect-1_171106200843.raw	Raw
	20171106_QX4_JeGe_SA_Pr5_C57_uninfect-2_171106225429.raw	Raw

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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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