Protective efficacy of a peptide derived from a potential adhesin of Pseudomonas aeruginosa against corneal infection.
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.
Shandong Provincial Key Laboratory of Ophthalmology, Shandong Provincial Excellent Innovation Team Program, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao 266071, China.
Qing
Q
Yuan
Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi'an 710069, China.
Yuting
Y
Wu
Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou 215006, China.
Yiqiang
Y
Wang
Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi'an 710069, China.
Lin
L
Chen
Shandong Provincial Key Laboratory of Ophthalmology, Shandong Provincial Excellent Innovation Team Program, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao 266071, China.
Mingli
M
Qu
Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi'an 710069, China.
Kangmin
K
Duan
Shandong Provincial Key Laboratory of Ophthalmology, Shandong Provincial Excellent Innovation Team Program, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao 266071, China; China Animal Health and Epidemiology Center, Qingdao, 266114, China. Electronic address: cathyge@163.com.
Ge
G
Zhao
D018829:Adhesins, Bacterial / Q000494:pharmacology*; D000818:Animals; D001422:Bacterial Adhesion / Q000187:drug effects; D058491:Bacterial Load; D001483:Base Sequence; D002478:Cells, Cultured; D015169:Colony Count, Microbial; D003320:Corneal Ulcer / Q000382:microbiology / Q000517:prevention & control*; D004797:Enzyme-Linked Immunosorbent Assay; D019573:Epithelium, Corneal / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D015818:Eye Infections, Bacterial / Q000382:microbiology / Q000517:prevention & control*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D020381:Interleukin-17; D037102:Lectins / Q000138:chemical synthesis / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D011552:Pseudomonas Infections / Q000382:microbiology / Q000517:prevention & control*; D011550:Pseudomonas aeruginosa / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D051198:Toll-Like Receptor 5 / Q000235:genetics
D018829:Adhesins, Bacterial; C508717:IL17A protein, human; D020381:Interleukin-17; D037102:Lectins; D010455:Peptides; D051198:Toll-Like Receptor 5; C038692:adhesin, Pseudomonas
Adhesin; Keratitis; Peptide; Protection; Pseudomonas aeruginosa