TY - JOUR
T1 - Protective efficacy of a peptide derived from a potential adhesin of Pseudomonas aeruginosa against corneal infection
AU - Yuan, Qing
AU - Wu, Yuting
AU - Wang, Yiqiang
AU - Chen, Lin
AU - Qu, Mingli
AU - Duan, Kangmin
AU - Zhao, Ge
N1 - Publisher Copyright:
© 2015 Elsevier Ltd.
PY - 2016/2/1
Y1 - 2016/2/1
N2 - Dissecting the interactions between Pseudomonas aeruginosa and corneal cells is important to identify a novel target for prevention and treatment of Pseudomonas keratitis. The current study began with a peptide identified by phage display, and was to investigate the protective efficacy against P. aeruginosa infection in cornea. The original peptide Pc-E, with high homology to a hypothetical membrane protein (HmpA) in P. aeruginosa, and the derived peptide Pc-EP, with the same sequence as a region in HmpA, were synthesized. Peptide Pc-EP could directly bind to HCEC, stronger than Pc-E, and specifically activate toll-like receptor 5, and thereby significantly induce the production of pro-inflammatory factors, such as IL-1β, IL-6, IFN-γ and IL-17. Moreover, Pc-EP could act as an antagonist to inhibit the adhesion of wild-type P. aeruginosa to HCEC and mouse corneas. No inhibitory effect was observed on the adhesion of the strain loss of HmpA. When compared to the wild-type strain, the adhesion of the hmpA mutant to corneal cells was significantly decreased. Treatment of infected mouse corneas with Pc-EP before infection significantly decreased the bacterial load in the cornea and attenuated the corneal pathology. These results indicate that Pc-EP can be a useful prophylactic agent for P. aeruginosa keratitis.
AB - Dissecting the interactions between Pseudomonas aeruginosa and corneal cells is important to identify a novel target for prevention and treatment of Pseudomonas keratitis. The current study began with a peptide identified by phage display, and was to investigate the protective efficacy against P. aeruginosa infection in cornea. The original peptide Pc-E, with high homology to a hypothetical membrane protein (HmpA) in P. aeruginosa, and the derived peptide Pc-EP, with the same sequence as a region in HmpA, were synthesized. Peptide Pc-EP could directly bind to HCEC, stronger than Pc-E, and specifically activate toll-like receptor 5, and thereby significantly induce the production of pro-inflammatory factors, such as IL-1β, IL-6, IFN-γ and IL-17. Moreover, Pc-EP could act as an antagonist to inhibit the adhesion of wild-type P. aeruginosa to HCEC and mouse corneas. No inhibitory effect was observed on the adhesion of the strain loss of HmpA. When compared to the wild-type strain, the adhesion of the hmpA mutant to corneal cells was significantly decreased. Treatment of infected mouse corneas with Pc-EP before infection significantly decreased the bacterial load in the cornea and attenuated the corneal pathology. These results indicate that Pc-EP can be a useful prophylactic agent for P. aeruginosa keratitis.
KW - Adhesin
KW - Keratitis
KW - Peptide
KW - Protection
KW - Pseudomonas aeruginosa
UR - http://www.scopus.com/inward/record.url?scp=84945277298&partnerID=8YFLogxK
U2 - 10.1016/j.exer.2015.10.011
DO - 10.1016/j.exer.2015.10.011
M3 - Article
C2 - 26500187
AN - SCOPUS:84945277298
SN - 0014-4835
VL - 143
SP - 39
EP - 48
JO - Experimental Eye Research
JF - Experimental Eye Research
ER -