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One major factor expressed by all clinical isolates of gram-negative bacteria is lipopolysaccharide (LPS); a second factor expressed by some<jats:italic>Escherichia coli<\/jats:italic>strains is a K1 polysaccharide capsule. To determine the role of the CD14 LPS receptor in the pathogenic effects of naturally occurring<jats:italic>E. coli<\/jats:italic>, the responses of CD14<jats:sup>\u2212\/\u2212<\/jats:sup>and CD14<jats:sup>+\/+<\/jats:sup>mice to three different isolates of<jats:italic>E. coli<\/jats:italic>obtained from sepsis patients were compared; two isolates express both smooth LPS and the K1 antigen, while the third isolate expresses only LPS and is negative for K1. An additional K1-positive isolate obtained from a newborn with meningitis and a K1-negative isogenic mutant of this strain were also used for these studies. CD14<jats:sup>\u2212\/\u2212<\/jats:sup>mice were resistant to the lethal effects of the K1-negative isolates. This resistance was accompanied by significantly lower levels of systemic tumor necrosis factor alpha (TNF-\u03b1) and interleukin-6 (IL-6) in these mice than in CD14<jats:sup>+\/+<\/jats:sup>mice, enhanced clearance of the bacteria, and significantly fewer additional gross symptoms. In contrast, CD14<jats:sup>\u2212\/\u2212<\/jats:sup>mice were as sensitive as CD14<jats:sup>+\/+<\/jats:sup>mice to the lethal effects of the K1-positive isolates, even though they had significantly lower levels of TNF-\u03b1 and IL-6 than CD14<jats:sup>+\/+<\/jats:sup>mice. These studies show that different bacterial isolates can use distinctly different mechanisms to cause disease and suggest that new, nonantibiotic therapeutics need to be directed against multiple targets.<\/jats:p>","DOI":"10.1128\/iai.00601-07","type":"journal-article","created":{"date-parts":[[2007,8,21]],"date-time":"2007-08-21T00:58:49Z","timestamp":1187657929000},"page":"5415-5424","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":15,"title":["Role of CD14 in Responses to Clinical Isolates of<i>Escherichia coli<\/i>: Effects of K1 Capsule Expression"],"prefix":"10.1128","volume":"75","author":[{"given":"Shalaka","family":"Metkar","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, CUNY Medical School, and Sophie Davis School for Biomedical Sciences, City College of New York, New York, New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shanjana","family":"Awasthi","sequence":"additional","affiliation":[{"name":"Center of Immunology and Inflammation, Laboratory of Innate Immunity, The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health Systems, Manhasset, New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erick","family":"Denamur","sequence":"additional","affiliation":[{"name":"Ecologie et e\u0301volution des micro-organismes, INSERM U722, Faculte\u0301 de Me\u0301decine Xavier Bichat, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kwang Sik","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophie C.","family":"Gangloff","sequence":"additional","affiliation":[{"name":"Center of Immunology and Inflammation, Laboratory of Innate Immunity, The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health Systems, Manhasset, New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saul","family":"Teichberg","sequence":"additional","affiliation":[{"name":"Center of Immunology and Inflammation, Laboratory of Innate Immunity, The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health Systems, Manhasset, New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alain","family":"Haziot","sequence":"additional","affiliation":[{"name":"Center of Immunology and Inflammation, Laboratory of Innate Immunity, The Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health Systems, Manhasset, New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jack","family":"Silver","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, CUNY Medical School, and Sophie Davis School for Biomedical Sciences, City College of New York, New York, New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanna M.","family":"Goyert","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, CUNY Medical School, and Sophie Davis School for Biomedical Sciences, City College of New York, New York, New York"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/00003246-199206000-00025"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1177\/09680519010070060901"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1996.6461357.x"},{"key":"e_1_3_2_5_2","first-page":"724","volume":"20","year":"1992","unstructured":"Bone, R. 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