Biomedical subjects
P Gemski
Publications and source records attributed to P Gemski.
Cellular release of heat-labile enterotoxin of Escherichia coli by bacteriophage induction.
Treatment of some enterotoxigenic Escherichia coli strains with the antibiotic mitomycin C resulted in lysis of the bacteria. Heat-labile enterotoxin (LT) activity of culture filtrates, determined by means of the Y-1 adrenal cell assay, increased dramatically as lysis of the culture proceeded. Further studies with E. coli strains 263 and B21-4 revealed that lysis is due to mitomycin C induction of vetetative development of a temperature bacteriophage. These findings suggest that the elevated levels of LT detected after mitomycin C treatment reflect the lytic release of cell-bound LT rather than the induction by mitomycin C of de novo toxin biosynthesis. Comparable increases in LT activity also resulted from thermal induction of a phage P1Cm lysogen of strain 263 or from sonic disruption of enterotoxigenic strains.
Interaction between bacteriophage Sf6 and Shigella flexner.
The Shigella flexneri phage Sf6 has an isometric head with hexagonal symmetry 53nm in diameter. The noncontractile tails in 16 nm long and terminates with a base plate containing six spikes. Sf6 is typical of the C phages in the morphological classification of Bradley. Phage Sf6 processes alpha-1,3-endorhamnosidase activity as demonstrated by methylation and reducing end group sugar analyses of the products obtained on interaction with the O-polysaccharide chain of S.flexneri strains which have the O-group 3,4 antigen. The major end product was an octasaccharide with the following structure: Rha III-GlcNAc-Rha I-Rha II-Rha III-GlcNAc-Rha I-Rha II. Acetylation of 0-2 of rhamnose III of the O-polysaccharide chain, either brought about by Sf6 lysogenization or found in wild-type S. flexneri (3b) strains, prevented enzymatic hydrolysis. O-deacetylation of the polysaccharide chain again made it susceptible to the S6f endorhamnosidase.
The role of Peyer's patches in the local immune response of rabbit ileum to live bacteria.
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Genetic studies of hybrids between coliphage lambda and salmonella phage P22: genetic analysis of the P22-lambda hybrid class.
P22-lambda hybrids which retain the protein coat of P22 have been isolated and characterized into two types. Type 1 hybrids which have the c through O-P genes of lambda are unable to grow lytically on Salmonella typhimurium. On the other hand, type 2 hybrids which contain only the c region of lambda, plated on S. typhimurium. Both hybrid types retained the generalized transducing and antigenic conversion capabilities of P22.
Studies with a new generation of oral attenuated shigella vaccine: Escherichia coli bearing surface antigens of Shigella flexneri.
In an attempt to develop a safe, proliferating, oral, attenuated vaccine against shigellosis, genes that control the synthesis of group- and type-specific somatic antigens of Shigella flexneri 2a were transferred via conjugation to a recipient strain of Escherichia coli. The resultant hybrid (E. coli expressing shigella surface antigens) vaccine strain, PGAI 42-1-15, believed to have a complete (smooth) lipopolysaccharide, was given to volunteers in two vaccination-challenge studies. The vaccine was well tolerated and gave evidence of intestinal proliferation. In trial no. 1, volunteers given two doses of vaccine one month apart were challenged after eight weeks with 10(4) virulent S. flexneri 2a. Attack rates were comparable in vaccinees (50%) and controls (40%). In trial no. 2, vaccinees were given three weekly doses of vaccine and were challenged four weeks later with a small inoculum (10(2)) of S. flexneri 2a. Again, attack rates among vaccinees (47%) and controls (39%) were similar. It is unclear why this theoretically ideal, live shigella vaccine failed to protect against S. flexneri 2a.
Biological properties of Shigella flexneri 2A toxin and its serological relationship to Shigella dysenteriae 1 toxin.
A toxin extracted from heat-inactivated, alkaline-treated Shigella flexneri 2a showed biological properties similar to those of Shigella dysenteria 1 toxin. The S, flexneri 2a toxin was lethal to mice, enterotoxic for ileal loops of rabbits, and cytotoxic for HeLa cells. A serological relationship between S. flexneri 2a and S. dysenteriae 1 toxin was shown with cross neutralization tests.
Inhibition of in vitro protein synthesis by Shigella dysenteriae 1 toxin.
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Studies on the pathogenesis of enteric infections caused by invasive bacteria.
Salmonellae, shigellae and some Escherichia coli must invade the intestinal epithelial cell and multiply within the mucosa to cause disease. Although the bacterial cell most likely possesses several properties essential to this invasive ability, the nature of the cell envelope complex is at present the only characteristic which has been implicated in this process. While a number of pathophysiological events result from invasion, some of our recent efforts have concerned the site and mechanism of intestinal fluid loss in salmonellosis and shigellosis. In both these disorders, bacterial invasion of the colonic mucosa, associated with an acute inflammatory reaction and mucosal damage, is regularly seen and colonic salt and water transport is abnormal. These defects may account for mild diarrhoea in salmonellosis and the dysenteric stools of shigellosis. However, in salmonella-infected animals with severe watery diarrhoea and in shigella-infected animals with diarrhoea alone or in combination with dysentery, the jejunum is in a net secretory state. This secretion occurs in the absence of bacterial invasion or morphological abnormalities. Thus, the diarrhoea caused by invasive bacteria may result from the inability of the colon to reabsorb the increased volume of fluid entering it from the small intestine. Although colonic mucosal damage is a feature of invasive-type diarrhoeas, the permeability of both the colon and small intestine to small molecules, mannitol and erythritol, is not altered. Thus intestinal fluid loss cannot be ascribed to transudation. In addition, the results of our Ussing chamber experiments, employing salmonella-infected rabbit ileum, reveal that salt and water secretion is an active process. Since secretion occurs in the jejunum in the absence of bacterial invasion, this might suggest the participation of an enterotoxin. Shigella dysenteriae I is the best-studied invasive organism in which an enterotoxin has been found, yet mutant strains which do not invade but retain the ability to elaborate enterotoxin fail to cause disease in either monkeys or man. Thus, the physiological relevance of Shiga enterotoxin and the mechanism of jejunal secretion in these disorders remain unclear. Recent data suggest that invasive enteropathogens, like the enterotoxin-producing bacteria, activate the mucosal adenylate cyclase-cyclic AMP system and that this activation may play a role in intestinal fluid secretion.
Studies on the pathogenesis of intestinal disease caused by invasive bacteria [proceedings].
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Extensive segments of the Escherichia coli K12 chromosome in Proteus mirabilis diploids.
Various Escherichia coli K12 Hfr donors transfer at low frequency portions of the E. coli genome to Proteus mirabilis. By remating such Proteus hybrids with the same or a different E. coli Hfr strain, other genetic characters could be added to yield diploid Proteus hybrids which contained more than 30 percent of the E. coli genome. The extent of the E. coli genetic material in these unstable Proteus diploid hybrids included segments with the following selected markers: gal, lac, ara, mel, mtl, and malA. Unselected markers known to map throughout this region of the chromosome were also detected in these hybrids. Among the markers expressed in Proteus hybrids with the E. coli malA region was the receptor site for coliphage lambda. Although plaques were not seen, lambda was adsorbed by the Proteus hybrids. Examination of DNA from the various Proteus hybrids by CsCl density gradient centrifugation showed a satellite component of E. coli DNA with a size that corresponded to the extent of the E. coli genome present as determined by genetic analysis.
Phage conversion of Shigella flexneri group antigens.
A temperate phage, designated Sf6, has been isolated from Shigella flexneri 3a. Characterization of Sf6 revealed that it possesses the capacity for converting the S. flexneri 3,4 group antigen complex to group factor 6. Serological studies and chemical analysis of lipopolysaccharide from converted strains suggest that group factor 6 is a reflection of an acetylation of the preexisting 3,4 antigen complex. Evidence is provided that the 3,4 group antigen complex functions, at least in part, as a cell surface receptor site for Sf6 adsorption.
An outbreak of Sonne shigellosis in a population receiving oral attenuated shigella vaccines.
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Invasion of HeLa cells by Salmonella typhimurium: a model for study of invasiveness of Salmonella.
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Formation of hybrids between coliphage lambda and Salmonella phage P22 with a Salmonella typhimurium hybrid sensitive to these phages.
An unusual Salmonella typhimurium hybrid with sensitivity to coliphage lambda and salmonella phage P22 has been recovered from matings between an Escherichia coli K-12 Hfr donor and an S. typhimurium recipient. The hybrid is an excellent host for achieving genetic recombination between lambda and P22. Two broad classes of hybrid phages were isolated. The lambda-P22 hybrid class, which has the protein coat of lambda, contains at least the c region of P22. The P22-lambda hybrid class has the protein coat of P22 and has inherited at least the c marker of lambda.
Mechanisms of Shigella pathogenesis.
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Shigellosis due to Shigella dysenteriae. 1. Relative importance of mucosal invasion versus toxin production in pathogenesis.
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