OprF/I-vaccinated sera inhibit binding of human interferon-gamma to Pseudomonas aeruginosa

Ding, Bin; Specht, Bernd-Ulrich von; Li, Yuanyi

doi:10.1016/j.vaccine.2010.04.028

Cited by 19 publications

(29 citation statements)

References 18 publications

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“…These results suggested that OprF is a host immune system sensor, modulating QS to enhance virulence when the bacteria are in contact with the host. Very interestingly, sera from OprF/I fusion protein-vaccinated humans inhibited P. aeruginosa binding to gamma interferon, suggesting a novel mechanism in which blocking of gamma interferon binding abrogates the virulence enhancement of P. aeruginosa, thereby contributing to efficient host defense against P. aeruginosa infection (24). In our experiments, no gamma interferon was present and the absence of OprF still reduced the QS network activity, indicating that OprF might sense signals other than gamma interferon.…”

Section: Vol 79 2011mentioning

confidence: 52%

Full Virulence of Pseudomonas aeruginosa Requires OprF

et al. 2011

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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.

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Section: Vol 79 2011mentioning

confidence: 52%

Full Virulence of Pseudomonas aeruginosa Requires OprF

et al. 2011

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“…OprF is highly conserved in pseudomonads, allowing the passage of small molecules across the outer membrane, and has been studied extensively as a vaccine candidate (15,35,36). Porins have also been described as acceptor molecules for C3b in Salmonella enterica serovar Typhimurium, Klebsiella pneumoniae, Neisseria meningitidis, and Legionella pneumophila (28,(37)(38)(39).…”

Section: Discussionmentioning

confidence: 99%

“…Understanding the molecular mechanism of C3 binding to bacterial surfaces offers a potential means for preventing and/or treating diseases caused by these Gram-negative pathogens. Moreover, since C3b binding to proteins greatly facilitates antigen presentation by antigen-presenting cells (50), C3b binding to OprF may be one mechanism whereby OprF serves as a potent vaccine (36,51).…”

Section: Figmentioning

confidence: 99%

Identification of OprF as a Complement Component C3 Binding Acceptor Molecule on the Surface of Pseudomonas aeruginosa

et al. 2015

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Pseudomonas aeruginosa is a versatile opportunistic pathogen that can cause devastating persistent infections. Complement is a highly conserved pathway of the innate immune system, and its role in the first line of defense against pathogens is widely appreciated. One of the earliest events in the complement cascade is the conversion of C3 to C3a and C3b, the latter typically binds to one or more acceptor molecules on the pathogen surface. We previously demonstrated that complement C3b binding acceptors exist on the P. aeruginosa surface. In the current study, we utilized either C3 polyclonal or C3b monoclonal antibodies in a farWestern technique followed by mass spectroscopy to identify the C3b acceptor molecule(s) on the P. aeruginosa surface. Our data provide evidence that OprF (an outer membrane porin, highly conserved in the Pseudomonadaceae) binds C3b. An oprFdeficient P. aeruginosa strain exhibits reduced C3 deposition compared to the wild type. We observed reduced internalization of oprF-deficient bacteria by neutrophils after opsonization compared with wild-type P. aeruginosa. Heterologous expression of OprF significantly enhanced C3b binding and increased serum-mediated bactericidal effects in complement-susceptible Escherichia coli. Furthermore, the predicted secondary structure of the C-terminal, surface-exposed region of OprF has high structural identity to the OmpA domain of several other Gram-negative bacteria, one of which is known to bind C3b. Therefore, these findings provide new insights into the biology of complement interactions with P. aeruginosa and other Gram-negative bacteria. Pseudomonas aeruginosa is an opportunistic nosocomial human pathogen that causes a wide range of clinical symptoms and infections in immunocompromised patients. This bacterium is often the causative agent of acute and chronic infections of the airway, sepsis, burn wounds, and skin infections. Excessive infiltration of neutrophils at the site of infection and the presence of complement have been observed in inflamed tissue and blood (1, 2). Serum sensitivity is directly dependent upon recognition of the bacterial surface by antibodies and complement (3). Prior studies also suggested that complement binds to the P. aeruginosa surface and enhances phagocytosis by acting as an opsonin (4). In this study, we sought to understand the consequences of complement interaction with P. aeruginosa. C3 is the central component of the complement system, playing a crucial role in the three major complement component activation processes. C3b, a product of C3 activation, binds covalently to bacterial surfaces through either a reactive intramolecular ester or an amide bond (5). C3b also participates in the formation of C5 convertase that cleaves C5 and initiates the sequential deposition of the remaining complement components to form the C5b-9 membrane attack complex (MAC), which may result in direct killing of microorganisms (6).The human complement system plays an important role in the clearance of early pulmonary P. aeruginosa inf...

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“…150 In a recent study it was demonstrated that OprF-OprI vaccinated sera from human volunteers inhibit P. aeruginosa binding to IFNγ, suggesting an additional effector mechanism of OprF containing vaccines. 151 OprI was demonstrated to adhere to the mucosal surfaces of the respiratory and intestinal tract and may so act as a mucosal carrier to facilitate antigen delivery to antigenpresenting cells. 152 In addition to conventionally extracted or recombinant protein preparations, Opr have been successfully tested in several other formulations including DNA vaccines, 129,130 peptide vaccine, 153 viral vectors, 154-159 dendritic cell-pulsed, 160 or heterologously expressed in bacterial vectors.…”

Section: Type III Secretion System Extracellular Toxins and Proteasesmentioning

confidence: 99%