Enterococcus faecalis Escapes Complement-Mediated Killing via Recruitment of Complement Factor H

Ali, Youssif M; Sim, Robert B.; Schwaeble, Wilhelm; Shaaban, Mona I.

doi:10.1093/infdis/jiz226

Cited by 11 publications

(5 citation statements)

References 43 publications

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“…Plates were washed as above and bound proteins were detected using rabbit anti-human L-ficolin, mouse anti-human CL-11 or mouse anti-human MBL mAbs. HRP conjugated goat anti-rabbit IgG followed by the colorimetric substrate ( 15 ).…”

Section: Materials and Reagentsmentioning

confidence: 99%

“…Serum samples were diluted in BBS (4 mM barbital, 145 mM NaCl, 2 mM CaCl 2 , 1 mM MgCl 2 , pH 7.4), starting at 5%, then added to the plates and incubated for 1.5 hours at 37°C. The plates were washed again, and bound C3b or C4b were detected using rabbit anti-human C3c (Dako) or rabbit anti-human C4c (Dako) followed by HRP conjugated goat anti-rabbit IgG followed by the colorimetric substrate TMB ( 15 ).…”

Section: Materials and Reagentsmentioning

confidence: 99%

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Lectin Pathway Mediates Complement Activation by SARS-CoV-2 Proteins

et al. 2021

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Early and persistent activation of complement is considered to play a key role in the pathogenesis of COVID-19. Complement activation products orchestrate a proinflammatory environment that might be critical for the induction and maintenance of a severe inflammatory response to SARS-CoV-2 by recruiting cells of the cellular immune system to the sites of infection and shifting their state of activation towards an inflammatory phenotype. It precedes pathophysiological milestone events like the cytokine storm, progressive endothelial injury triggering microangiopathy, and further complement activation, and causes an acute respiratory distress syndrome (ARDS). To date, the application of antiviral drugs and corticosteroids have shown efficacy in the early stages of SARS-CoV-2 infection, but failed to ameliorate disease severity in patients who progressed to severe COVID-19 pathology. This report demonstrates that lectin pathway (LP) recognition molecules of the complement system, such as MBL, FCN-2 and CL-11, bind to SARS-CoV-2 S- and N-proteins, with subsequent activation of LP-mediated C3b and C4b deposition. In addition, our results confirm and underline that the N-protein of SARS-CoV-2 binds directly to the LP- effector enzyme MASP-2 and activates complement. Inhibition of the LP using an inhibitory monoclonal antibody against MASP-2 effectively blocks LP-mediated complement activation. FACS analyses using transfected HEK-293 cells expressing SARS-CoV-2 S protein confirm a robust LP-dependent C3b deposition on the cell surface which is inhibited by the MASP-2 inhibitory antibody. In light of our present results, and the encouraging performance of our clinical candidate MASP-2 inhibitor Narsoplimab in recently published clinical trials, we suggest that the targeting of MASP-2 provides an unsurpassed window of therapeutic efficacy for the treatment of severe COVID-19.

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Section: Materials and Reagentsmentioning

confidence: 99%

Section: Materials and Reagentsmentioning

confidence: 99%

Lectin Pathway Mediates Complement Activation by SARS-CoV-2 Proteins

et al. 2021

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“…28 . many types of bacteria have developed the same mechanism via attraction of factor H to their surface and escape from complement mediated killing like Neisseria species 29 , Streptococcus pyogenes 30 , Streptococcus pneumoniae 31 , Borrelia species 32 , Acinetobacter baumannii 33 and Enterococcus faecalis 34 .…”

Section: Discussionmentioning

confidence: 99%

Characterization of complement activation on the surface of klebsiella pneumoniae

Rabie

Said

Kenawy

et al. 2021

Egyptian Journal of Medical Microbiology

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Background: Life threatening infections caused by the opportunistic pathogen K. pneumoniae are one of the most serious infections that elevate mortality rate in hospitals, worldwide. K. pneumoniae develops several mechanisms for avoiding killing by the complement system for survival in the host. The complement system is the first line of immune defense against different bacteria including K. pneumoniae. Objective: In this study we assessed the role of complement system in killing of both serum resistant and serum sensitive strains of K. pneumoniae. Methodology: Six clinical isolates of K. pneumoniae were collected from urine, sputum and the blood samples from patients in Mansoura Hospitals University. Serum bactericidal effect was assessed and confirmed by Turbidimetric method, Complement mediated lysis, complements C3b deposition and fH binding were assessed by ELISA. Results: our results demonstrated that complement mediated killing of K. pneumoniae is driven via the Alternative pathways, it was found that a lower C3b deposition via AP and a higher fH binding to surface of serum resistant K. pneumoniae strains compared with serum sensitive K. pneumoniae Conclusions: This study explains the role of complement system in killing K. pneumoniae and how serum resistant strains escape the immune defense via sequestering complement factor H.

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“…Several conventional techniques are commonly applied to detecting microorganisms including conventional culture methods [11,12], immunological techniques (e.g., enzymelinked immunosorbent assays) [13][14][15], and polymerase chain reactions [16,17]. In spite of their recognition accuracy, most of these techniques are laborious, time-consuming and costly [18,19].…”

Section: Introductionmentioning

confidence: 99%

A Potentiometric Electronic Tongue as a Discrimination Tool of Water-Food Indicator/Contamination Bacteria

et al. 2021

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Microorganism assessment plays a key role in food quality and safety control but conventional techniques are costly and/or time consuming. Alternatively, electronic tongues (E-tongues) can fulfill this critical task. Thus, a potentiometric lab-made E-tongue (40 lipid sensor membranes) was used to differentiate four common food contamination bacteria, including two Gram positive (Enterococcus faecalis, Staphylococcus aureus) and two Gram negative (Escherichia coli, Pseudomonas aeruginosa). Principal component analysis and a linear discriminant analysis-simulated annealing algorithm (LDA-SA) showed that the potentiometric signal profiles acquired during the analysis of aqueous solutions containing known amounts of each studied bacteria allowed a satisfactory differentiation of the four bacterial strains. An E-tongue-LDA-SA model (12 non-redundant sensors) correctly classified 98 ± 5% of the samples (repeated K-fold-CV), the satisfactory performance of which can be attributed to the capability of the lipid membranes to establish electrostatic interactions/hydrogen bonds with hydroxyl, amine and/or carbonyl groups, which are comprised in the bacteria outer membranes. Furthermore, multiple linear regression models, based on selected subsets of E-tongue sensors (12–15 sensors), also allowed quantifying the bacteria contents in aqueous solutions (0.993 ± 0.011 ≤ R2 ≤ 0.998 ± 0.005, for repeated K-fold-CV). In conclusion, the E-tongue could be of great value as a preliminary food quality and safety diagnosis tool.

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Enterococcus faecalis Escapes Complement-Mediated Killing via Recruitment of Complement Factor H

Cited by 11 publications

References 43 publications

Lectin Pathway Mediates Complement Activation by SARS-CoV-2 Proteins

Lectin Pathway Mediates Complement Activation by SARS-CoV-2 Proteins

Characterization of complement activation on the surface of klebsiella pneumoniae

A Potentiometric Electronic Tongue as a Discrimination Tool of Water-Food Indicator/Contamination Bacteria

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