Full Virulence of Pseudomonas aeruginosa Requires OprF

Abstract

OprF is a general outer membrane porin of Pseudomonas aeruginosa, a well-known human opportunistic pathogen associated with severe hospital-acquired sepsis and chronic lung infections of cystic fibrosis patients. A multiphenotypic approach, based on the comparative study of a wild-type strain of P. aeruginosa, its isogenic oprF mutant, and an oprF-complemented strain, showed that OprF is required for P. aeruginosa virulence. The absence of OprF results in impaired adhesion to animal cells, secretion of ExoT and ExoS toxins through the type III secretion system (T3SS), and production of the quorum-sensing-dependent virulence factors pyocyanin, elastase, lectin PA-1L, and exotoxin A. Accordingly, in the oprF mutant, production of the signal molecules N-(3-oxododecanoyl)-L-homoserine lactone and N-butanoyl-L-homoserine lactone was found to be reduced and delayed, respectively. Pseudomonas quinolone signal (PQS) production was decreased, while its precursor, 4-hydroxy-2-heptylquinoline (HHQ), accumulated in the cells. Taken together, these results show the involvement of OprF in P. aeruginosa virulence, at least partly through modulation of the quorum-sensing network. This is the first study showing a link between OprF, PQS synthesis, T3SS, and virulence factor production, providing novel insights into virulence expression.

Role of Pseudomonas aeruginosa Peptidoglycan-Associated Outer Membrane Proteins in Vesicle Formation

“…4B and C). Recent evidence partially conflicts with these results, determining that a P. aeruginosa oprF mutant produces lower levels of PQS (67). Our study likely contradicts this study due to the fact that different quantification methods were used: Fito-Boncompte et al (67) used an LC/MS method (68) to quantify PQS, and this study used TLC.…”

“…Recent evidence partially conflicts with these results, determining that a P. aeruginosa oprF mutant produces lower levels of PQS (67). Our study likely contradicts this study due to the fact that different quantification methods were used: Fito-Boncompte et al (67) used an LC/MS method (68) to quantify PQS, and this study used TLC. In contrast to Fito-Boncompte et al, we and others have found that in the absence of a chelator in the mobile phase, PQS is difficult to quantify using liquid chromatography (66, 69) due to poor peak resolution; thus, TLC provides a more quantifiable approach.…”

Mucosal and systemic antibody responses to potentialPseudomonas aeruginosavaccine protein antigens in young children with cystic fibrosis following colonization and infection

“…OprF is an outer membrane porin and an important virulence factor. 32 OprH provides stability to the outer membrane through interaction with lipopolysaccharide, 33 while OprG has potential porin function. 34 A literature search did not reveal any vaccine studies on OprH or OprG.…”

Chronic Infection by Mucoid Pseudomonas aeruginosa Associated with Dysregulation in T-Cell Immunity to Outer Membrane Porin F

“…OprF binds IFN-g, leading to stimulation of the quorum-sensing network (40). Oprf deletion mutants define a role of OprF in virulence, partly through modulation of quorum-sensing (41). In light of this evidence for OprF immunogenicity and hyperexpression during biofilm formation, it might be predicted that patients undergoing such infection would show enhanced OprF adaptive immunity: it has previously been shown by others and confirmed by us that chronic infection is associated with raised antibody titers (6,37).…”