Composition of and Physiopathology produced by Plague Endotoxins

Walker, Richard V.; Barnes, Marshall G.; Higgins, Edward

doi:10.1038/2091246a0

Cited by 16 publications

(10 citation statements)

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“…There have been increasing efforts recently to isolate toxic lipopolysaccharides from P. Vestis. 34 The delay between the onset of a logarithmic growth rate of the organism at 6 to 12 hours after infection" and the appearance of edema some 48 to 60 hours later may indicate that it is necessary for a certain quantity of toxin to accumulate in the tissues before edema is produced. Prowleus studies demonstrated that 1. gegtto acquires resistance to phagocytosis by neutrophils after a certain period of infection.is…”

Section: Discussionmentioning

confidence: 99%

Pneumonic Plague in Monkeys: An Electron Microscope Study

Finegold¹

1968

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The Infection of monkey vngaS by Pasteurelia Peipif was studied with the electron microscope. The disease was fizst apparent clinically at 60 to 70 hours and pathologically &t 72 hours. At this time, the initial response seen with the light sicroscope was alveolar edema with massive proliferation of c•anisms. With the electron microscope, interstitial edema around veins and bronchi was the earliest observed response to the presence of numerous intra-alveoler bacilli. Earty in the disease, before the onset of a leukocytic exudate, interstitial fluid also accumulated in the form of subepithelial blebe. No evidence of significant vascular damage was found to accouut for the marked increate in permeability, even with the aid of intravenous injections of colloidal carbon prior to sacrifice. Leukocytic and mast cell factors iu the pathogenesis of the edema appear unlikely. Once the cellular comopnent of the reaction developed, P. a resisted both phagocytosis by polymorphonuclear neutrophils and intracellular digestion by iononuclear phagocytea. Invasion of the tissues by the organism was observed only in the advanced stages of the pneumonia, when all components of the alveolar septa were undergoing necrosis. 1IPneumonic plague is characterized by extensive intra-alveolar edema containing myriads of Pasteurella pestis prior to any significant leukocytic exudate or damage to lung tissueT, when studied by light microscopy.Infected edema fluid is al'so found at the margins of consolidated areas and is the initial change in secondary lesions. 1Other bacterial pneumonias, such as pneumococcal, seem to have a similar pathogenesis, both in the rare human cases with abbreviated disease due to intervening accident? and in experimental animals, 3 but they differ from plague in the more rapid addition of leukocytes, fibrin, and red blood cells to the exudate.The electron microscope has been successfully employed in\ the study of a variety of inflammatory reactions and their components, such as leukocyte migration,' phagocytosis, 5 0 5 and vascular permeability,' but there have been few reports of the ultrastructural manifestations of bacterial pneumonia.•feIn view of the value of electron microscopy in detecting tissue damage in experimental pulmonary edema prior to the appearance of lesions visible with the light microscope,8's it seemed appropriate to examine the lungs of animals exposed to aerosols of P.. pestis in order to describe the ultrastructural changes in necrotizing pneumonia and, hopefully, to determine the pathogenesis of the extensive, early edema. II. MATFTIALS AND EIIODSA. ANIMALS Rhesus monkeys (Macac& mulatta) imported from India were housed locally for at least 90 days before use. Young adults of both sexes weighing between 2.6 and 3.25 kg were housed in paire and were fed Purina monkey chow* a"d water ad libitum. Tuberculin testing was performed monthly, and ot.'-o :negative reactors were used. B. ORGANISH AND EXPOSURESThe KIM-10 strain of P. Pestis was used. The isolation, maintenance, and cultural characte...

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Section: Discussionmentioning

confidence: 99%

Pneumonic Plague in Monkeys: An Electron Microscope Study

Finegold¹

1968

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“…Endotoxin was extracted and isolated by a slight modification of a general method adapted by Tauber and Russell (21) from the earlier procedure described by Westphal et al (26). Our particular application of Tauber and Russell's general extraction and isolation procedure is described in some detail, because their procedure has not been previously used for the isolation of P. pestis endotoxin and because plague endotoxin obtained by their method was considerably more toxic than plague endotoxin previously reported (7,24,25). A 90-ml amount of cold, sterile, double-distilled water was added to each 100-g quantity of frozen, packed, washed P. pestis cells, and the thawed cell suspension (12 to 14 C) was stirred in a Waring Blendor for 2 min at low speed (final temperature, 17 to 19 C).…”

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“…Production of the localized Shwartzman reaction in rabbits. Each of eight New Zealand white rabbits (2 to 2.5 kg) of equally mixed sex was injected intradermally (in a shaved abdominal area) with 25 ,ug of P. pestis endotoxin contained in 0.1 ml of sterile double-distilled water. An adjacent area on the opposite side of the ventral abdominal line was injected intradermally with 0.1 ml of sterile double-distilled water as a control.…”

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Isolation and Biological Characterization of Pasteurella pestis Endotoxin

Albizo¹,

Surgalla²

1970

Infect Immun

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Endotoxin containing 2.1 % nitrogen, 1.6% phosphorus, 22.5 % neutral hexose, 15% hexosamine, 25% esterified and amide-linked fatty acids, and 1.4% protein was isolated from Pasteurella pestis strain Alexander by slight modification of a method adapted by Tauber and Russell. The lipopolysaccharide exhibited classical endotoxic biological properties including: (i) toxicity in mice, guinea pigs, and rabbits; (ii) antigenicity in rabbits; (iii) capacity to evoke a biphasic pyrogenic response in rabbits; (iv) capacity to induce tolerance in mice to the lethal effect of endotoxin; (v) capacity to stimulate rapidly acquired resistance in mice to bacterial infection, and (vi) the capacity to produce the localized and generalized Shwartzman phenomena in rabbits. Findings obtained during the study concerning the occurrence, isolation, toxicity, and other biological properties of P. pestis endotoxin provide new evidence that endotoxin could contribute to death in plague. Early plague investigators proposed that Pasteurella pestis produced an endotoxin that contributed to death in plague (14). Early efforts to isolate the endotoxin by classical methods were unsuccessful (8, 9); however, in more recent attempts the phenol extraction method of Westphal et al. (26) has been used, and considerable success has been achieved (7, 24, 25). It is now known collectively from the studies of Davies (7), Walker et al. (25), Walker (23, 24), and Larrabee et al. (11) that P. pestis produces a lipopolysaccharide that kills mice, guinea pigs, rabbits, and monkeys with symptoms and pathological changes characteristic of endotoxin shock at death. These recent findings lend direct support to the endotoxic death concept in plague proposed by earlier investigators. The present investigation, which involved isolating P. pestis endotoxin and testing the toxic and biological properties of the endotoxin, was undertaken to provide additional knowledge concerning P. pestis endotoxin and to determine whether endotoxin could contribute significantly to the pathogenesis of plague. MATERIALS AND METHODS Stock culture. Fully virulent (guinea pig-passed) P. pestis strain Alexander (LD=o < 20 cells for mice and guinea pigs) possessing fraction I antigen, VW antigens, pigmentation, and pesticinogeny was used as a stock culture. Cultivation of organisms. Blood Agar Base slants (Difco, pH 6.8) were inoculated with stock P. pestis

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“…Since then, this highly pathogenic bacterium has been investigated, and many virulence factors have been identified, including fraction 1 antigen, murine toxin, Yop proteins, pH 6 antigen, and iron acquisition systems (5,28). Lipopolysaccharide (LPS) has also been studied for many decades as one of the virulence factors of Y. pestis, and its composition and endotoxic activity have been examined in earlier studies (1,40,41). By use of modern analytical methods, the LPS of Y. pestis was proven to be a rough type LPS without O-antigenic polysaccharide (7,8,25,29,30,35) that contains 3-hydroxy-myristic acid (3-OH-C 14:0 ) as a main fatty acid in the lipid A portion.…”

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Modification of the Structure and Activity of Lipid A inYersinia pestisLipopolysaccharide by Growth Temperature

et al. 2002

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Yersinia pestis strain Yreka was grown at 27 or 37°C, and the lipid A structures (lipid A-27°C and lipid A-37°C) of the respective lipopolysaccharides (LPS) were investigated by matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry. Lipid A-27°C consisted of a mixture of tri-acyl, tetra-acyl, penta-acyl, and hexa-acyl lipid A's, of which tetra-acyl lipid A was most abundant. Lipid A-37°C consisted predominantly of tri-and tetra-acylated molecules, with only small amounts of penta-acyl lipid A; no hexa-acyl lipid A was detected. Furthermore, the amount of 4-amino-arabinose was substantially higher in lipid A-27°C than in lipid A-37°C. By use of mouse and human macrophage cell lines, the biological activities of the LPS and lipid A preparations were measured via their abilities to induce production of tumor necrosis factor alpha (TNF-␣). In both cell lines the LPS and the lipid A from bacteria grown at 27°C were stronger inducers of TNF-␣ than those from bacteria grown at 37°C. However, the difference in activity was more prominent in human macrophage cells. These results suggest that in order to reduce the activation of human macrophages, it may be more advantageous for Y. pestis to produce less-acylated lipid A at 37°C.Yersinia pestis was isolated as a causative agent of plague in Hong-Kong in 1894 independently by A. Yersin and S. Kitasato (3). Since then, this highly pathogenic bacterium has been investigated, and many virulence factors have been identified, including fraction 1 antigen, murine toxin, Yop proteins, pH 6 antigen, and iron acquisition systems (5, 28). Lipopolysaccharide (LPS) has also been studied for many decades as one of the virulence factors of Y. pestis, and its composition and endotoxic activity have been examined in earlier studies (1,40,41). By use of modern analytical methods, the LPS of Y. pestis was proven to be a rough type LPS without O-antigenic polysaccharide (7,8,25,29,30,35) that contains 3-hydroxy-myristic acid (3-OH-C 14:0 ) as a main fatty acid in the lipid A portion. However, there was a discrepancy in the amounts of the nonhydroxy-fatty acids found. Hartley et al. reported that nearly 90% of fatty acids in the lipid A of Y. pestis strain 195/R (a virulent strain) consisted of 3-OH-C 14:0 (14). On the other hand, considerable amounts of lauric acid (C 12:0 ), palmitic acid (C 16:0 ), and palmitoleic acid (C 16:1 ) were detected in the lipid A of Y. pestis strain EV40 (an avirulent strain) (4, 39). Using the same strain, Aussel et al. (2) proposed a hexa-acylated lipid A structure (four molecules of 3-OH-C 14:0 , one of C 12:0 , and one of C 16:1 ). In our preliminary experiment we isolated the lipid A from Y. pestis strain Yreka (virulent strain) grown at 37°C and found that it contained 3-OH-C 14:0 and only trace amounts of other fatty acids. A possible explanation of the controversy on fatty acids may be differences in strains or culture conditions. Darveau et al. (8) reported that the molecular size of the LPS from Y. pestis strain EV76 ...

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Composition of and Physiopathology produced by Plague Endotoxins

Cited by 16 publications

References 2 publications

Pneumonic Plague in Monkeys: An Electron Microscope Study

Pneumonic Plague in Monkeys: An Electron Microscope Study

Isolation and Biological Characterization of Pasteurella pestis Endotoxin

Modification of the Structure and Activity of Lipid A inYersinia pestisLipopolysaccharide by Growth Temperature

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