{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T07:04:03Z","timestamp":1781766243379,"version":"3.54.5"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2019,5,6]],"date-time":"2019-05-06T00:00:00Z","timestamp":1557100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,8,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Enterococcus faecalis is considered to be the most important species of enterococci responsible for blood stream infections in critically ill patients. In blood, the complement system is activated via the classical pathway (CP), the lectin pathway (LP), or the alternative pathway (AP), and it plays a critical role in opsonophagocytosis of bacteria including E faecalis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In a mouse model of enterococcus peritonitis, BALB-C mice were challenged with a high dose of E faecalis 12 hours after intraperitoneal administration of anti-Factor H (FH) antibodies or isotype control. Four hours later, control mice developed higher bacterial burden in blood and organs compared with mice treated with anti-FH antibodies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We demonstrate that complement recognition molecules C1q, CL-11, and murine ficolin-A bind the enterococcus and drive the CP and the LP in human and mouse. We further describe that E faecalis evades the AP by recruitment of FH on its surface. Our results show a strong C3b deposition on E faecalis via both the CP and the LP but not through the AP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings indicate that E faecalis avoids the complement phagocytosis by the AP via sequestering complement FH from the host blood.<\/jats:p><\/jats:sec>","DOI":"10.1093\/infdis\/jiz226","type":"journal-article","created":{"date-parts":[[2019,5,2]],"date-time":"2019-05-02T03:14:50Z","timestamp":1556766890000},"page":"1061-1070","source":"Crossref","is-referenced-by-count":11,"title":["Enterococcus faecalis Escapes Complement-Mediated Killing via Recruitment of Complement Factor H"],"prefix":"10.1093","volume":"220","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3124-9848","authenticated-orcid":false,"given":"Youssif M","family":"Ali","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy, Mansoura University, Egypt"},{"name":"Department of Veterinary Medicine, School of Biological Sciences, University of Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert B","family":"Sim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Oxford University, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilhelm","family":"Schwaeble","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, School of Biological Sciences, University of Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona I","family":"Shaaban","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy, Mansoura University, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,5,6]]},"reference":[{"key":"2019080903145449300_CIT0001","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1177\/154411130401500506","article-title":"Virulence factors of Enterococcus faecalis: relationship to endodontic disease","volume":"15","author":"Kayaoglu","year":"2004","journal-title":"Crit Rev Oral Biol Med"},{"key":"2019080903145449300_CIT0002","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1590\/S1413-86702007000300010","article-title":"Nosocomial bloodstream infections: organisms, risk factors and resistant phenotypes in the Brazilian University Hospital","volume":"11","author":"Ribas","year":"2007","journal-title":"Braz J Infect Dis"},{"key":"2019080903145449300_CIT0003","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00378-17","article-title":"Enterococcus faecalis promotes innate immune suppression and polymicrobial catheter-associated urinary tract infection","volume":"85","author":"Tien","year":"2017","journal-title":"Infect Immun"},{"key":"2019080903145449300_CIT0004","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1080\/00365540600868321","article-title":"Enterococcal bacteraemia: epidemiological, microbiological, clinical and prognostic characteristics, and the impact of high level gentamicin resistance","volume":"38","author":"Shaked","year":"2006","journal-title":"Scand J Infect Dis"},{"key":"2019080903145449300_CIT0005","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1016\/j.vaccine.2003.11.027","article-title":"Enterococcal infections: host response, therapeutic, and prophylactic possibilities","volume":"22","author":"Koch","year":"2004","journal-title":"Vaccine"},{"key":"2019080903145449300_CIT0006","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1128\/CDLI.12.8.930-934.2005","article-title":"Naturally acquired antibodies against four Enterococcus faecalis capsular polysaccharides in healthy human sera","volume":"12","author":"Hufnagel","year":"2005","journal-title":"Clin Diagn Lab Immunol"},{"key":"2019080903145449300_CIT0007","doi-asserted-by":"crossref","first-page":"5551","DOI":"10.1128\/IAI.00576-09","article-title":"Enterococcus faecalis capsular polysaccharide serotypes C and D and their contributions to host innate immune evasion","volume":"77","author":"Thurlow","year":"2009","journal-title":"Infect Immun"},{"key":"2019080903145449300_CIT0008","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1128\/IAI.01473-06","article-title":"Extracellular gelatinase of Enterococcus faecalis destroys a defense system in insect hemolymph and human serum","volume":"75","author":"Park","year":"2007","journal-title":"Infect Immun"},{"key":"2019080903145449300_CIT0009","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1078\/0171-2985-00146","article-title":"The mannan-binding lectin-associated serine proteases (MASPs) and MAp19: four components of the lectin pathway activation complex encoded by two genes","volume":"205","author":"Schwaeble","year":"2002","journal-title":"Immunobiology"},{"key":"2019080903145449300_CIT0010","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/nri800","article-title":"Evolution of the lectin-complement pathway and its role in innate immunity","volume":"2","author":"Fujita","year":"2002","journal-title":"Nat Rev Immunol"},{"key":"2019080903145449300_CIT0011","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.imbio.2007.10.009","article-title":"Ficolins: novel pattern recognition molecules of the innate immune response","volume":"213","author":"Runza","year":"2008","journal-title":"Immunobiology"},{"key":"2019080903145449300_CIT0012","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/j.imbio.2011.12.008","article-title":"Structure and function of collectin liver 1 (CL-L1) and collectin 11 (CL-11, CL-K1)","volume":"217","author":"Selman","year":"2012","journal-title":"Immunobiology"},{"key":"2019080903145449300_CIT0013","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1177\/09680519050110011001","article-title":"Production and purification of recombinants of mouse MASP-2 and sMAP","volume":"11","author":"Iwaki","year":"2005","journal-title":"J Endotoxin Res"},{"key":"2019080903145449300_CIT0014","doi-asserted-by":"crossref","first-page":"8234","DOI":"10.1074\/jbc.M109.065805","article-title":"A novel mannose-binding lectin\/ficolin-associated protein is highly expressed in heart and skeletal muscle tissues and inhibits complement activation","volume":"285","author":"Skjoedt","year":"2010","journal-title":"J Biol Chem"},{"key":"2019080903145449300_CIT0015","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1042\/bj2430507","article-title":"Resolution and analysis of \u2018native\u2019 and \u2018activated\u2019 properdin","volume":"243","author":"Farries","year":"1987","journal-title":"Biochem J"},{"key":"2019080903145449300_CIT0016","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1084\/jem.163.4.837","article-title":"Purification and characterization of a membrane protein (gp45-70) that is a cofactor for cleavage of C3b and C4b","volume":"163","author":"Seya","year":"1986","journal-title":"J Exp Med"},{"key":"2019080903145449300_CIT0017","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1084\/jem.156.6.1739","article-title":"Unique role of the complement receptor CR1 in the degradation of C3b associated with immune complexes","volume":"156","author":"Medof","year":"1982","journal-title":"J Exp Med"},{"key":"2019080903145449300_CIT0018","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S0167-5699(98)01376-0","article-title":"Does properdin crosslink the cellular and the humoral immune response?","volume":"20","author":"Schwaeble","year":"1999","journal-title":"Immunol Today"},{"key":"2019080903145449300_CIT0019","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/S0161-5890(03)00110-X","article-title":"The regulation of the complement system: insights from genetically-engineered mice","volume":"40","author":"Turnberg","year":"2003","journal-title":"Mol Immunol"},{"key":"2019080903145449300_CIT0020","doi-asserted-by":"crossref","first-page":"4857","DOI":"10.1093\/hmg\/ddt336","article-title":"Genetic influences on plasma CFH and CFHR1 concentrations and their role in susceptibility to age-related macular degeneration","volume":"22","author":"Ansari","year":"2013","journal-title":"Hum Mol Genet"},{"key":"2019080903145449300_CIT0021","first-page":"251","article-title":"Attachment of the soluble complement regulator factor H to cell and tissue surfaces: relevance for pathology","volume":"19","author":"J\u00f3zsi","year":"2004","journal-title":"Histol Histopathol"},{"key":"2019080903145449300_CIT0022","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.molimm.2004.02.005","article-title":"The human complement factor H: functional roles, genetic variations and disease associations","volume":"41","author":"Rodriguez de Cordoba","year":"2004","journal-title":"Mol Immunol"},{"key":"2019080903145449300_CIT0023","doi-asserted-by":"crossref","first-page":"8761","DOI":"10.1073\/pnas.1019338108","article-title":"Common polymorphisms in C3, factor B, and factor H collaborate to determine systemic complement activity and disease risk","volume":"108","author":"Heurich","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2019080903145449300_CIT0024","doi-asserted-by":"crossref","first-page":"1820","DOI":"10.1093\/infdis\/jiw029","article-title":"Complement factor H serum levels determine resistance to pneumococcal invasive disease","volume":"213","author":"van der Maten","year":"2016","journal-title":"J Infect Dis"},{"key":"2019080903145449300_CIT0025","doi-asserted-by":"crossref","first-page":"28263","DOI":"10.1074\/jbc.M109.009225","article-title":"Synergy between ficolin-2 and pentraxin 3 boosts innate immune recognition and complement deposition","volume":"284","author":"Ma","year":"2009","journal-title":"J Biol Chem"},{"key":"2019080903145449300_CIT0026","doi-asserted-by":"crossref","first-page":"e1002793","DOI":"10.1371\/journal.ppat.1002793","article-title":"The lectin pathway of complement activation is a critical component of the innate immune response to pneumococcal infection","volume":"8","author":"Ali","year":"2012","journal-title":"PLoS Pathog"},{"key":"2019080903145449300_CIT0027","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.imbio.2011.10.001","article-title":"Absence of the lectin activation pathway of complement does not increase susceptibility to Pseudomonas aeruginosa infections","volume":"217","author":"Kenawy","year":"2012","journal-title":"Immunobiology"},{"key":"2019080903145449300_CIT0028","doi-asserted-by":"crossref","first-page":"e1002793","DOI":"10.1371\/journal.ppat.1002793","article-title":"The lectin pathway of complement activation is a critical component of the innate immune response to pneumococcal infection","volume":"8","author":"Ali","year":"2012","journal-title":"PLoS Pathog"},{"key":"2019080903145449300_CIT0029","doi-asserted-by":"crossref","first-page":"5301","DOI":"10.1073\/pnas.1401011111","article-title":"Low-dose recombinant properdin provides substantial protection against Streptococcus pneumoniae and Neisseria meningitidis infection","volume":"111","author":"Ali","year":"2014","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2019080903145449300_CIT0030","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.clim.2018.08.009","article-title":"Recombinant chemotaxis inhibitory protein of Staphylococcus aureus (CHIPS) protects against LPS-induced lung injury in mice","volume":"197","author":"Ali","year":"2018","journal-title":"Clin Immunol"},{"key":"2019080903145449300_CIT0031","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1128\/IAI.00863-08","article-title":"Neutrophils are essential for rapid clearance of Enterococcus faecium in mice","volume":"77","author":"Leendertse","year":"2009","journal-title":"Infect Immun"},{"key":"2019080903145449300_CIT0032","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/S0002-9440(10)63953-3","article-title":"Fas (CD95) induces alveolar epithelial cell apoptosis in vivo: implications for acute pulmonary inflammation","volume":"158","author":"Matute-Bello","year":"2001","journal-title":"Am J Pathol"},{"key":"2019080903145449300_CIT0033","doi-asserted-by":"crossref","first-page":"2323","DOI":"10.1001\/jama.2009.1754","article-title":"International study of the prevalence and outcomes of infection in intensive care units","volume":"302","author":"Vincent","year":"2009","journal-title":"JAMA"},{"key":"2019080903145449300_CIT0034","doi-asserted-by":"crossref","first-page":"37769","DOI":"10.1074\/jbc.M112.358283","article-title":"Secondary cell wall polymers of Enterococcus faecalis are critical for resistance to complement activation via mannose-binding lectin","volume":"287","author":"Geiss-Liebisch","year":"2012","journal-title":"J Biol Chem"},{"key":"2019080903145449300_CIT0035","doi-asserted-by":"crossref","first-page":"6096","DOI":"10.4049\/jimmunol.1002185","article-title":"Collectin 11 (CL-11, CL-K1) is a MASP-1\/3-associated plasma collectin with microbial-binding activity","volume":"185","author":"Hansen","year":"2010","journal-title":"J Immunol"},{"key":"2019080903145449300_CIT0036","doi-asserted-by":"crossref","first-page":"e38196","DOI":"10.1371\/journal.pone.0038196","article-title":"The interaction pattern of murine serum ficolin-A with microorganisms","volume":"7","author":"Hummelsh\u00f8j","year":"2012","journal-title":"PLoS One"},{"key":"2019080903145449300_CIT0037","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/0161-5890(80)90119-4","article-title":"The physiological breakdown of the third component of human complement","volume":"17","author":"Harrison","year":"1980","journal-title":"Mol Immunol"},{"key":"2019080903145449300_CIT0038","doi-asserted-by":"crossref","first-page":"5587","DOI":"10.1128\/IAI.62.12.5587-5594.1994","article-title":"Resistance of Enterococcus faecium to neutrophil-mediated phagocytosis","volume":"62","author":"Arduino","year":"1994","journal-title":"Infect Immun"},{"key":"2019080903145449300_CIT0039","doi-asserted-by":"crossref","first-page":"3426","DOI":"10.4049\/jimmunol.180.5.3426","article-title":"Human factor H interacts selectively with Neisseria gonorrhoeae and results in species-specific complement evasion","volume":"180","author":"Ngampasutadol","year":"2008","journal-title":"J Immunol"},{"key":"2019080903145449300_CIT0040","doi-asserted-by":"crossref","first-page":"426","DOI":"10.4049\/jimmunol.1102545","article-title":"Acquisition of complement factor H is important for pathogenesis of Streptococcus pyogenes infections: evidence from bacterial in vitro survival and human genetic association","volume":"188","author":"Haapasalo","year":"2012","journal-title":"J Immunol"},{"key":"2019080903145449300_CIT0041","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1007\/s00018-016-2418-4","article-title":"Complement factor H in host defense and immune evasion","volume":"74","author":"Parente","year":"2017","journal-title":"Cell Mol Life Sci"},{"key":"2019080903145449300_CIT0042","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.febslet.2009.11.087","article-title":"Sialic acids acquired by Pseudomonas aeruginosa are involved in reduced complement deposition and siglec mediated host-cell recognition","volume":"584","author":"Khatua","year":"2010","journal-title":"FEBS Lett"},{"key":"2019080903145449300_CIT0043","doi-asserted-by":"crossref","first-page":"E3040","DOI":"10.1073\/pnas.1424391112","article-title":"Regulation of age-related macular degeneration-like pathology by complement factor H","volume":"112","author":"Toomey","year":"2015","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2019080903145449300_CIT0044","doi-asserted-by":"crossref","first-page":"e1005043","DOI":"10.1371\/journal.ppat.1005043","article-title":"Virulence of group A streptococci is enhanced by human complement inhibitors","volume":"11","author":"Ermert","year":"2015","journal-title":"PLoS Pathog"},{"key":"2019080903145449300_CIT0045","doi-asserted-by":"crossref","first-page":"16969","DOI":"10.1073\/pnas.012669199","article-title":"The classical pathway is the dominant complement pathway required for innate immunity to Streptococcus pneumoniae infection in mice","volume":"99","author":"Brown","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2019080903145449300_CIT0046","doi-asserted-by":"crossref","first-page":"5301","DOI":"10.1073\/pnas.1401011111","article-title":"Low-dose recombinant properdin provides substantial protection against Streptococcus pneumoniae and Neisseria meningitidis infection","volume":"111","author":"Ali","year":"2014","journal-title":"Proc Natl Acad Sci U S A"}],"container-title":["The Journal of Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jid\/advance-article-pdf\/doi\/10.1093\/infdis\/jiz226\/28939748\/jiz226.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jid\/article-pdf\/220\/6\/1061\/29113103\/jiz226.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,12,9]],"date-time":"2020-12-09T17:38:54Z","timestamp":1607535534000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jid\/article\/220\/6\/1061\/5485924"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,6]]},"references-count":46,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2019,5,6]]},"published-print":{"date-parts":[[2019,8,9]]}},"URL":"https:\/\/doi.org\/10.1093\/infdis\/jiz226","relation":{},"ISSN":["0022-1899","1537-6613"],"issn-type":[{"value":"0022-1899","type":"print"},{"value":"1537-6613","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,9,15]]},"published":{"date-parts":[[2019,5,6]]}}}