Abstract
Pseudomonas aeruginosa is a ubiquitous opportunistic pathogen, which causes infectious disease in patients with cystic fibrosis and compromised immunity. P. aeruginosa is difficult to eradicate because of its intrinsic resistance to most traditional antibiotics as well as acquired resistance mechanisms after decades of antibiotic usage. A full understanding of the P. aeruginosa pathogenesis mechanisms is necessary for the development of novel prevention and treatment strategies. To identify novel vaccine candidates, here we comprehensively examined the expression levels of all the known outer membrane proteins in two P. aeruginosa strains in a murine acute pneumonia model. OprH was one of the most highly expressed proteins during infection. In addition, OprH is known to be highly immunogenic and accessible by host proteins. Thus, it was chosen as a vaccine candidate. To further identify vaccine candidates, 34 genes highly expressed during infection were evaluated for their contributions in virulence by testing individual transposon insertion mutants. Among them, fpvA, hasR, and foxA were found essential for bacterial virulence and therefore included in vaccine construction. Immunization with a mixture of FpvA, HasR, and FoxA rendered no protection, however, while immunization by OprH refolded in liposomes elicited specific opsonic antibodies and conferred protection against two lipopolysaccharide-heterologous P. aeruginosa strains (PA14 and PA103). Overall, by studying the expression profile of the P. aeruginosa outer membrane proteins during infection, we identified OprH as a potential vaccine candidate for the prevention of lung infection by P. aeruginosa.
Highlights
Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen which can cause various human infections, especially in immunocompromised and cystic fibrosis patients [1, 2]
In several acute and chronic infection models, animals were protected by immunization with various surface exposed immunogens, including lipopolysaccharide (LPS) O antigen [6], the type III secretion system (T3SS) component PcrV [7], outer membrane protein F (OprF) [8], flagellin [9], and pillin [10]
Our study indicates that OprH is a potential candidate for vaccine development against P. aeruginosa infection
Summary
Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen which can cause various human infections, especially in immunocompromised and cystic fibrosis patients [1, 2]. In several acute and chronic infection models, animals were protected by immunization with various surface exposed immunogens, including lipopolysaccharide (LPS) O antigen [6], the type III secretion system (T3SS) component PcrV [7], outer membrane protein F (OprF) [8], flagellin [9], and pillin [10]. Immunization with these immunogens elicits protective antibodies which mediate opsonophagocytic killing and/or virulence inhibition. Recent studies have been focused on antigens with conserved epitopes
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