Effect of Pseudomonas aeruginosa elastase and alkaline protease on serum complement and isolated components C1q and C3

Hong, Yuqun; Ghebrehiwet, Berhane

doi:10.1016/0090-1229(92)90065-v

Cited by 135 publications

(96 citation statements)

References 34 publications

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“…Comparing Efb to various other C3-binding proteins from numerous pathogens (Table II) revealed that the majority of these proteins are surface-associated and from intracellular pathogens (exceptions being T. cruzi and P. aeruginosa) (32,34,77) (Table II), and all except P. aeruginosa (77) utilize these proteins primarily as a means of gaining entry into cells via CR1/2 (Table II). In addition, these proteins range in size, and their predicted secondary structures vary significantly.…”

Section: Discussionmentioning

confidence: 99%

Identification and Characterization of the C3 Binding Domain of the Staphylococcus aureus Extracellular Fibrinogen-binding Protein (Efb)

Lee

Liang

Höök

et al. 2004

Journal of Biological Chemistry

115

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The secreted Staphylococcus aureus extracellular fibrinogen-binding protein (Efb) is a virulence factor that binds to both the complement component C3b and fibrinogen. Our laboratory previously reported that by binding to C3b, Efb inhibited complement activation and blocked opsonophagocytosis. We have now located the Efb binding domain in C3b to the C3d fragment and determined a disassociation constant (K d ) of 0.24 M for the Efb-C3d binding using intrinsic fluorescence quenching assays. Using truncated, recombinant forms of Efb, we also demonstrate that the C3b binding region of Efb is located within the C terminus, in contrast to the fibrinogen binding domains that are located at the N-terminal end of the protein. Enzyme-linked immunosorbent assay-type binding assays demonstrated that recombinant Efb could bind to both C3b and fibrinogen simultaneously, forming a trimolecular complex and that the C-terminal region of Efb could inhibit complement activity in vitro. In addition, secondary structure analysis using circular dichroism spectroscopy revealed that the C-terminal, C3b binding region of Efb is composed primarily of ␣-helices, suggesting that this domain of Efb represents a novel type of C3b-binding protein.

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Section: Discussionmentioning

confidence: 99%

Identification and Characterization of the C3 Binding Domain of the Staphylococcus aureus Extracellular Fibrinogen-binding Protein (Efb)

Lee

Liang

Höök

et al. 2004

Journal of Biological Chemistry

115

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“…Elongation factor Tuf, a 43-kDa surface protein, was identified as the first Factor H, FHL-1, and CFHR1-binding protein of this Gram-negative pathogen (11). In addition, P. aeruginosa secretes the endogenous proteases elastase and alkaline protease, which degrade and inactivate human complement components, including C1q, C2, and C3b (12,13). Degradation of the opsonin C3b reduces phagocytosis of the pathogen by human neutrophils, and degradation of C3 inhibits fibroblast cell growth (12,14,15).…”

mentioning

confidence: 99%

“…In addition, P. aeruginosa secretes the endogenous proteases elastase and alkaline protease, which degrade and inactivate human complement components, including C1q, C2, and C3b (12,13). Degradation of the opsonin C3b reduces phagocytosis of the pathogen by human neutrophils, and degradation of C3 inhibits fibroblast cell growth (12,14,15). In addition, P. aeruginosa produces an alginate layer that forms a mechanical barrier and that reduces the accessibility and the action of host complement proteins and other plasma defense factors (16).…”

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confidence: 99%

Dihydrolipoamide Dehydrogenase of Pseudomonas aeruginosa Is a Surface-Exposed Immune Evasion Protein That Binds Three Members of the Factor H Family and Plasminogen

Hallström

Mörgelin

Barthel

et al. 2012

The Journal of Immunology

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The opportunistic human pathogen Pseudomonas aeruginosa causes a wide range of diseases. To cross host innate immune barriers, P. aeruginosa has developed efficient strategies to escape host complement attack. In this study, we identify the 57-kDa dihydrolipoamide dehydrogenase (Lpd) as a surface-exposed protein of P. aeruginosa that binds the four human plasma proteins, Factor H, Factor H-like protein-1 (FHL-1), complement Factor H-related protein 1 (CFHR1), and plasminogen. Factor H contacts Lpd via short consensus repeats 7 and 18–20. Factor H, FHL-1, and plasminogen when bound to Lpd were functionally active. Factor H and FHL-1 displayed complement-regulatory activity, and bound plasminogen, when converted to the active protease plasmin, cleaved the chromogenic substrate S-2251 and the natural substrate fibrinogen. The lpd of P. aeruginosa is a rather conserved gene; a total of 22 synonymous and 3 nonsynonymous mutations was identified in the lpd gene of the 5 laboratory strains and 13 clinical isolates. Lpd is surface exposed and contributes to survival of P. aeruginosa in human serum. Bacterial survival was reduced when Lpd was blocked on the surface prior to challenge with human serum. Similarly, bacterial survival was reduced up to 84% when the bacteria was challenged with complement active serum depleted of Factor H, FHL-1, and CFHR1, demonstrating a protective role of the attached human regulators from complement attack. In summary, Lpd is a novel surface-exposed virulence factor of P. aeruginosa that binds Factor H, FHL-1, CFHR1, and plasminogen, and the Lpd-attached regulators are relevant for innate immune escape and most likely contribute to tissue invasion.

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“…The elastase breaks down host proteins such as collagen, immunoglobulins, and complement proteins [6]. Alkaline protease is a an enzyme that cleaves various components, such as complement C1q and C3 [7], and prevents TLR5 activation through flagellin destruction [8].…”

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confidence: 99%

Molecular Detection of the VirulentExoUGenotype ofPseudomonas aeruginosaIsolated from Infected Surgical Incisions

Hassuna

2016

Surgical Infections

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Background: Pseudomonas aeruginosa is one of the major pathogens responsible for hospital-acquired infections, which harbor a wide array of virulence factors. The main aim of this study was to determine the frequency of the virulent ExoU genotype in relation to the ExoS genotype among isolated P. aeruginosa from infected surgical incisions, followed by phylogenetic analysis. Methods: A total of 66 P. aeruginosa isolates were identified by cultural and biochemical characteristics. All isolates were tested for antimicrobial susceptibility against the following antimicrobial agents: imipenem, amikacin, gentamicin, amoxycillin, cefotaxime, cefepime, and levofloxacin. Molecular detection of the ExoS and ExoU as well as two other virulence genes was done by polymerase chain reaction (PCR). Sequencing of ExoU gene and phylogenetic analysis was performed.Results: Approximately 81% of the isolated P. aeruginosa were multi-drug resistant. The ExoS genotype was more prevalent (63%) among the isolates than the ExoU genotype (18%), with 9% of the isolates possessing both toxins. LasB and AprA were detected in 63.6% and 27.2% of the isolates, respectively. An association was observed between the number of virulence genes and the presence of multi-drug resistance. All the ExoU were multi-drug resistant (MDR), whereas 71% of the ExoS were MDR. Phylogenetic analysis of ExoU gene showed a 99% similarity with four different strains. Conclusion: Despite the greater frequency of the ExoS genotype, the presence of the virulent MDR ExoU genotype isolates from surgical site infections is an alarming sign requiring further intervention and investigations.

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Effect of Pseudomonas aeruginosa elastase and alkaline protease on serum complement and isolated components C1q and C3

Cited by 135 publications

References 34 publications

Identification and Characterization of the C3 Binding Domain of the Staphylococcus aureus Extracellular Fibrinogen-binding Protein (Efb)

Identification and Characterization of the C3 Binding Domain of the Staphylococcus aureus Extracellular Fibrinogen-binding Protein (Efb)

Dihydrolipoamide Dehydrogenase of Pseudomonas aeruginosa Is a Surface-Exposed Immune Evasion Protein That Binds Three Members of the Factor H Family and Plasminogen

Molecular Detection of the VirulentExoUGenotype ofPseudomonas aeruginosaIsolated from Infected Surgical Incisions

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