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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have suggested that the lipopolysaccharide (LPS, endotoxin) component of the gram-negative bacterial cell wall is a key virulence factor that serves to enhance mortality during infections in which fungi and gram-negative bacteria are copathogens. To test this hypothesis, mice were challenged ip with Escherichia coli 0111:B4, Candida albicans, or both, and the effect of administration of anti-E. coli 0111:B4 LPS monoclonal antibody (mAb) 8G9 on endotoxemia, bacteremia, and mortality was assessed. E. coli (2 x 10(7) colony-forming units (CFU)) plus C. albicans (6 x 10(7) CFU) infection produced 100% mortality at 7 days, compared to the relatively low mortality caused by infection with either E. coli or C. albicans alone (20 and 3%, respectively, P less than 0.01). Administration of mAb 8G9 to animals receiving both pathogens reduced mortality (100% versus 14%, P less than 0.05), endotoxemia (3653 +/- 3187 versus 2 +/- 2 endotoxin units (EU), P less than 0.01), and bacteremia (4.2 +/- 2.3 versus 1.1 +/- 2.1 log(CFU/ml), P less than 0.01) compared to animals receiving saline alone. In a separate series of experiments, purified E. coli 0111:B4 LPS was administered in place of viable E. coli. The simultaneous injection of 200 micrograms E. coli LPS and C. albicans (6 x 10(7) CFU) produced 93% mortality at 7 days, compared to the low mortality that occurred following injection with either E. coli 0111:B4 LPS or C. albicans alone (21 and 3% respectively, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endotoxin promotes synergistic lethality during concurrent Escherichia coli and Candida albicans infection. 152 27

The molecular basis of central nervous system invasiveness by Haemophilus influenzae has been studied by using genetically defined mutants and in vivo and in vitro model systems. Capsular polysaccharide and lipopolysaccharide are important microbial determinants of the ability of H. influenzae to traverse the nasopharynx and localize in the cerebrospinal fluid and meninges after bacteremia. The genes for type b capsule confer greater invasive potential than do those for other capsular polysaccharides, although the molecular basis for this is not understood. Mutants have also indicated the role of lipopolysaccharide in enhancing the efficiency of bacterial translocation from the nose to the blood and in facilitating intravascular survival. Organisms that localize successfully in the blood and central nervous system are the progeny of a small fraction of the original challenge inoculum, often a single bacterium.
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PMID:Molecular basis of invasive Haemophilus influenzae type b disease. 158 86

The incidence and mortality, pathogenesis, clinical manifestations, and management of sepsis and the sepsis syndrome are reviewed, and the use of antiendotoxin monoclonal antibodies to treat patients with sepsis is discussed. The sepsis syndrome and septic shock are induced by the presence of endotoxin, a lipopolysaccharide found in the outer membrane of gram-negative bacteria. Proper management of gram-negative sepsis includes appropriate antimicrobial therapy, fluids and electrolytes, nutritional support, administration of vasopressors, and mechanical ventilation if necessary. To date, two antiendotoxin monoclonal antibodies have been produced and subjected to extensive clinical testing. HA-1A, a human cell line-derived monoclonal immunoglobulin M (IgM) antibody that contains only a small fragment of murine protein, was tested in one trial. HA-1A significantly reduced mortality in patients with sepsis and gram-negative bacteremia and produced better resolution of major morbidities than placebo in those patients. E5, an IgM antibody produced entirely via murine monoclonal antibody technology, was evaluated in two trials. Results from the first trial showed that E5 significantly reduced mortality in patients with gram-negative infection who were not in refractory shock. In contrast, results from the second trial did not show any significant reduction in mortality among patients with gram-negative infection who received E5. However, resolution of major morbidities occurred more frequently among E5 recipients in both trials. HA-1A and E5 were both well tolerated in the trials. The cost of therapy is expected to be $3000-$4000 per treatment course. The antiendotoxin monoclonal antibodies represent the next step along the path toward important reductions in morbidity and mortality from gram-negative infection. However, the financial implications of the use of HA-1A and E5 are enormous, and stringent patient selection criteria for administration of these products will have to be developed.
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PMID:Gram-negative sepsis, the sepsis syndrome, and the role of antiendotoxin monoclonal antibodies. 161 15

To test the hypothesis that walls of air capillaries are a site for Escherichia coli to pass the air-blood barrier, fimbriated and nonfimbriated strains of E. coli were inoculated intratracheally into 18-day-old turkeys. Venous blood was cultured, and turkeys were necropsied from 0.5 to 8 hours post-inoculation. Lungs were processed for histopathology and electron microscopy. E. coli 078 was identified ultrastructurally using rabbit anti-lipopolysaccharide antibody and protein A-colloidal gold. All birds developed bacteremia; there was no significant difference between groups given fimbriated or nonfimbriated bacteria. Bacteria adhered to the plasma membrane of air capillary epithelial cells and were seen within vacuoles of portions of these cells that lined the fornices of air capillaries. Bacteria were also seen in the basement membrane at the basal surface of air capillary epithelial cells and, rarely, in vacuoles of subjacent endothelial cells. Infected granular and non-granular cells that lined air atria were necrotic 4 hours post-inoculation. Bacteria were within the overlying trilaminar substance and between reticular fibers of the interstitial stroma and pleura at 30 minutes post-infection and thereafter. Thus, the pulmonary air capillaries are a site for entrance of E. coli into the pulmonary blood capillaries, but fimbriae play little or no role in passage across the air-blood barrier.
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PMID:Ultrastructural studies of the lung of turkeys (Meleagris gallopavo) inoculated intratracheally with Escherichia coli. 167 5

Three attenuated Salmonella typhi strains have been constructed by introducing deletions in aroC and aroD or deletions in cya and crp into one of two wild-type parent strains, Ty2 or ISP1820. These mutant strains were designated CVD 906 (ISP1820 delta aroC delta aroD), CVD 908 (Ty2 delta aroC delta aroD), and chi 3927 (Ty2 delta cya delta crp). Two studies were conducted with 36 healthy adult inpatient volunteers to determine in a double-blind fashion the safety and immunogenicity of approximately 5 x 10(4) and 5 x 10(5) CFU of each of these three vaccine candidates given as a single dose. No statistically significant difference in the incidence of reactions among vaccinees was observed. Fever (oral temperature greater than or equal to 38.2 degrees C) occurred in 2 of 12 volunteers who received CVD 906, in 0 of 12 who received CVD 908, and in 1 of 12 who received chi 3927. Vaccine bacteremia without symptoms occurred in 1 of 12 vaccinees who received CVD 906, in 0 of 12 who received CVD 908, and in 2 of 12 who received chi 3927. Overall, 19 (53%) of 36 vaccinees developed immunoglobulin G antibody to S. typhi lipopolysaccharide after vaccination, with no statistically significant differences in the rate of seroconversion among volunteers in the three groups. We conclude that defined mutations in the aromatic biosynthetic pathway and in the cyclic AMP global regulatory system attenuate S. typhi. Mutant strains CVD 906, CVD 908, and chi 3927 are highly (and approximately equally) immunogenic but possibly differ in their propensity to induce fever. Further studies are needed to document the apparent relative safety of CVD 908 as a typhoid vaccine and as a vaccine carrier of foreign antigens.
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PMID:Comparison of the safety and immunogenicity of delta aroC delta aroD and delta cya delta crp Salmonella typhi strains in adult volunteers. 173 Apr 87

In this paper clinical and experimental studies are reviewed for evidence that monoclonal antibodies (MoAbs), directed against common epitopes in the core glycolipid region of lipopolysaccharide (LPS) of gram-negative bacteria, protect against the lethal effect of bacteremia of serologically unrelated gram-negative bacteria. Only those experimental studies that included control MoAbs and excluded the possibility of survival due to endotoxin tolerance, provided evidence for the protective efficacy of cross-reactive MoAbs. Two recently performed clinical trials evaluating the protective value of the MoAbs HA-1A and E5 showed beneficial effects (enhanced survival) by each MoAb in different subgroups of patients with proven gram-negative bacterial infections. It is concluded that immunotherapy by MoAbs is a promising new tool in the treatment of gram-negative bacterial septic shock. However, the pathophysiological mechanism of protection remains to be elucidated and the group of patients which may benefit most remains to be defined more clearly. Therefore, further experimental and clinical studies are warranted.
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PMID:Life-saving immunotherapy with cross-reactive monoclonal antibodies against endotoxin: a critical evaluation of experimental and clinical studies. 179 79

The rapid quantitation of bacteria in blood was achieved by using a novel assay method for gram-negative bacterial lipopolysaccharide (endotoxin, LPS). The assay involves the capture of specific LPS onto microtiter plates by means of monoclonal antibodies directed against the oligosaccharide region of the LPS, followed by detection of the bound LPS by a chromogenic Limulus amebocyte lysate (LAL) system. This immunolimulus (IML) assay combines the specificity of monoclonal antibodies with the sensitivity of the LAL system to achieve the first specific, sensitive quantitation of bioactive endotoxin in plasma. In the animal model tested, Haemophilus influenzae type b (Hib) bacteremia in infant rats, there was a strong correlation between IML results and the concentration of Hib colony-forming units in blood samples (r = .845, P less than .001). Using antibodies with appropriate specificities, this approach should be useful for rapid detection of a wide range of gram-negative bacteria and endotoxins in blood.
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PMID:Detection of experimental Haemophilus influenzae type b bacteremia and endotoxemia by means of an immunolimulus assay. 185 84

A mixture of five IgM human monoclonal antibodies (MAbs) against lipopolysaccharide antigens of Pseudomonas aeruginosa, plus a human IgG1 MAb against exotoxin A, were studied in 12 noninfected patients and 8 patients with P. aeruginosa bacteremia or pneumonia (or both). The preparation was well tolerated over a dose range of 0.3-1.2 ml/kg (0.75-3.0 mg/kg IgM protein). After a single infusion of 1.2 ml/kg (3.0 mg/kg IgM protein), serum antibody titers were boosted into therapeutic range, with serum half-lives ranging from 34 to 99 h. Also, opsonophagocytic activity in serum rose more than 1 log10 for all but one antibody. In no patient was an immunologic response against the MAb preparation detected.
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PMID:Safety, pharmacokinetics, and functional activity of human anti-Pseudomonas aeruginosa monoclonal antibodies in septic and nonseptic patients. 844 Sep 53

To elucidate the clinical significance of serum-sensitivity of respiratory pathogenic Pseudomonas aeruginosa (P. aeruginosa) strains, we examined serum-sensitivity of P. aeruginosa isolated from 16 patients with lower respiratory tract infections and clinical backgrounds of these patients. We also evaluated the virulence of four serum-resistant and four serum-sensitive P. aeruginosa strains in murine pneumonia model induced by intratracheal challenge, and the silver-stained profiles of purified lipopolysaccharide (LPS) from these strains. Serum-sensitive strains were isolated only from patients with chronic bronchitis, bronchiectasis, and diffuse panbronchiolitis colonized with P. aeruginosa, and rarely caused pneumonias, while serum-resistant strains caused pneumonias in some cases. Intratracheal challenge of mice with 5 x 10(7) cfu per mouse of a serum resistant strain caused fatal hemorrhagic pneumonia with bacteremia. In contrast, the same dose of a serum-sensitive strain provided non-fatal pneumonia without bacteremia. LD50 of serum-sensitive strains in a murine model of P. aeruginosa pneumonia were at least 2-10 times higher than those of serum-resistant strain. The LPS profiles of two serum-resistant strains and one serum-sensitive strain showed ladder-like patterns. The similar analysis demonstrated that one serum-sensitive strain was lack of ladder-like patterns. These data support that serum-sensitive P. aeruginosa strains are less virulent than serum-resistant P. aeruginosa strains in the lower respiratory tract, and serum sensitivity of P. aeruginosa strains is determined by the structure of the O-side chain of LPS; either lack of the O-side chain or the presence of sparse O-side chain.
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PMID:[Serum sensitivity of Pseudomonas aeruginosa isolated from sputum as a virulence factor in the lower respiratory tract]. 191 Jan 22

Despite the advent of aminoglycoside and beta-lactam antibiotics and early antimicrobial intervention, overall morbidity and mortality associated with gram-negative sepsis and bacteremia remain high. Complications of sepsis have been related to the release of endotoxin from the cell walls of gram-negative bacilli. Although antibiotics can effectively kill gram-negative bacteria, they have no effect on lipopolysaccharide lipopolysaccharide (LPS) and may, in fact, enhance its release when cell lysis occurs. Lipid A, the lipid portion of LPS, is composed of glucosamines, polar phosphate groups, and fatty acids. It represents the endotoxic component of gram-negative bacteria and is responsible for host responses to LPS, including fever, hypotension, and shock. E5 is a murine monoclonal immunoglobulin M antibody directed against the lipid A portion of the cell-wall endotoxin that is common to clinically important gram-negative bacilli. A clinical evaluation program of E5 included patients who were moderately to severely ill with clinical evidence of an infection usually caused by gram-negative bacteria. In pharmacokinetic and safety studies, laboratory tests revealed no evidence of antibody-mediated toxicity and serum antibody concentrations in the desired therapeutic range (greater than 5 microgramS/mL) were found as late as 72 hours after initial infusion of E5. In a Phase II study, mortality rates at seven days in patients with documented gram-negative infection were 22 percent in the placebo group compared with 7 percent in the E5-treated groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:E5 monoclonal immunoglobulin M antibody for the treatment of gram-negative sepsis. 194 40


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