Samuel B. Formal

Representative Shigella flexneri strains were studied to determine whether plasmids are involved in their virulence. All invasive S. flexneri strains, irrespective of serotype, were found to harbor a large plasmid of approximately 140 megadaltons in size, although some strains carried additional plasmid species. Spontaneous variants of strains of serotypes 1, 2, and 5 had lost this 140-megadalton plasmid and had concomitantly become avirulent, i.e., could neither invade HeLa cell monolayers nor produced keratoconjunctivitis in guinea pigs. To monitor plasmid transfer, the 140-megadalton plasmid of strain M90T (serotype 5) was tagged with the kanamycin resistance transposon Tn5. This tagged plasmid, pWR110, was not self-transmissible, but was mobilized by one of several different conjugative plasmids into avirulent derivatives of the heterologous serotypes 1 and 2 which had lost the comparable large plasmid. Transconjugants of both serotypes which had received pWR110 regained virulence. These data directly demonstrate that this large S. flexneri plasmid encodes or regulates some function(s) required for epithelial cell penetration.

Two Escherichia coli strains isolated in Vietnam from American soldiers with diarrhea and acute "colitis" were examined for virulence in both in vitro and in vivo experimental models. Their biologic properties were compared with those of an enterotoxin-producing Esch. coli strain implicated in disease of swine as well as with those of four other Esch. coli and a virulent shigella strain. The two Vietnam strains produced an enterotoxin in a rabbit ileal-loop model and in volunteers caused a diarrheal syndrome resembling that of cholera. Two nontoxigenic Esch. coli strains gave evidence of penetrating epithelial cells in laboratory models and caused a shigella-like illness in man characterized by dysentery, tenesmus, urgency, hyperpyrexia and hypotension with systemic toxemia. Thus, strains of Esch. coli can cause disease in man by at least two mechanisms: elaboration of a cholera-like enterotoxin; and shigella-like intestinal epithelial penetration.

LaBrec, Eugene H., Herman Schneider, Thomas J. Magnani, and Samuel B. Formal. Epithelial cell penetration as an essential step in the pathogenesis of bacillary dysentery. J. Bacteriol. 88:1503-1518. 1964.-A parent strain of Shigella flexneri 2a and a colonial mutant derived from it were studied in three animal models. Both strains were equally virulent for mice when living cells suspended in hog gastric mucin were injected by the intraperitoneal route. Feeding the parent strain to starved guinea pigs, followed by the intraperitoneal injection of opium, resulted in the formation of ulcerative lesions in the intestinal tract and in the death of these animals. When the colonial variant was fed to similarly prepared animals, the animals survived and the intestinal tract remained normal. The parent produced diarrheal symptoms and intestinal lesions after its oral administration to rhesus monkeys; the variant caused neither symptoms nor pathology in this species. Studies were carried out to define the characteristics present in the parent strain and absent in the colonial mutant, which would enable the parent to produce ulcerative lesions of the bowel and death in the guinea pig model or intestinal lesions and diarrheal symptoms in the monkey. Neither serological studies nor growth studies conducted both in vitro and in vivo offered a clue to explain this difference. The virulent parent strain was shown to penetrate the bowel epithelium and enter the lamina propria; the avirulent mutant did not do this. Entrance to the lamina propria was by way of the epithelial cell of the mucosa. The avirulent mutant did not possess the capacity to penetrate this cell. This observation was extended to show that the virulent parent possesses the ability to infect and multiply within HeLa cells; furthermore, the organisms are able to penetrate epithelial cells of the guinea pig cornea, causing ulcerative lesions. The avirulent variant possesses neither of these capacities. It is suggested that epithelial cell penetration is a major factor in determining the pathogenicity of dysentery bacilli.

Journal Article Inoculum Size in Shigellosis and Implications for Expected Mode of Transmission Get access Herbert L. DuPont, Herbert L. DuPont University of Maryland School of Medicine, Division of Infectious Diseases, Baltimore Please address requests for reprints to Dr. Herbert DuPont, University of Texas Health Science Center at Houston, 6400 West Cullen Street, Houston, TX 77030. Search for other works by this author on: Oxford Academic PubMed Google Scholar Myron M. Levine, Myron M. Levine University of Maryland School of Medicine, Division of Infectious Diseases, Baltimore Search for other works by this author on: Oxford Academic PubMed Google Scholar Richard B. Hornick, Richard B. Hornick University of Maryland School of Medicine, Division of Infectious Diseases, Baltimore Search for other works by this author on: Oxford Academic PubMed Google Scholar Samuel B. Formal Samuel B. Formal University of Maryland School of Medicine, Division of Infectious Diseases, Baltimore Search for other works by this author on: Oxford Academic PubMed Google Scholar The Journal of Infectious Diseases, Volume 159, Issue 6, June 1989, Pages 1126–1128, https://doi.org/10.1093/infdis/159.6.1126 Published: 01 June 1989 Article history Received: 30 September 1988 Revision received: 16 December 1988 Published: 01 June 1989

Escherichia coli K-12 acquired the ability to produce a high titer of Shiga-like toxin after lysogenization by either of two different bacteriophages isolated from a highly toxinogenic Escherichia coli O157:H7 strain that causes hemorrhagic colitis. One of these phages and another Shiga-like toxin-converting phage from an Escherichia coli O26 isolate associated with infantile diarrhea were closely related in terms of morphology, virion polypeptides, DNA restriction fragments, lysogenic immunity, and heat stability, although a difference in host range was noted. These phages are currently the best-characterized representatives from a broader family of Shiga-like toxin-converting phages.