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Dipyridamole is an effective inhibitor of cardiovirus growth in cell culture. The effects of dipyridamole on mengovirus replication in vivo and in vitro were examined in the hope the drug could be used as an experimental analog of the poliovirus inhibitor guanidine. Guanidine selectively inhibits poliovirus RNA synthesis but not RNA translation, and as such, has been a valuable research tool. Although guanidine does not inhibit cardiovirus infection, a compound with similar discriminatory characteristics would be experimentally useful for parallel work with these viruses. We found that mengovirus plaque formation in HeLa or L cells was inhibited nearly 100% by the presence of 80 muM dipyridamole. The inhibitory effect was reversible and targeted an early step in the replication cycle. Studies with luciferase-expressing mengovirus replicons showed that viral protein synthesis was unaffected by dipyridamole, and rather, RNA synthesis was the step targeted by the drug. This assessment was confirmed by direct analyses of viral translation and RNA synthesis activities in a Krebs-2-derived in vitro system that supported complete, infectious cardiovirus replication. In Krebs extracts, dipyridamole specifically inhibited viral RNA synthesis to more than 95%, with no concomitant effect on viral protein translation or polyprotein processing. The observed inhibition reversibly affected an early step in both minus-strand and plus-strand RNA synthesis, although inhibition of plus-strand synthesis was more profound than that of minus-strand synthesis. We conclude that dipyridamole is a potent experimental tool that readily distinguishes between cardiovirus translation and RNA replication functions.

Biopsies taken during colonoscopic examination of the human large bowel were used to examine the relationship of the commensal bacterial to the mucosal epithelial cell surface. Bacteria were seen adhering to the exposed epithelial cell surface and also to the mucus sheet. Isolation of aerobic organisms showed that Escherichia coli are closely associated with the gut wall throughout the large intestine. One strain of E. coli predominated in each biopsy, and this strain was present along the whole length of bowel. Adhesion of bacteria to the gut wall does occur in vivo and may be one of the factors involved in the ability of an organism to colonize and persist.

It has been shown that some, but not all, Escherichia coli strains isolated from urine adhere, in vitro, to the surface of uroepithelial or vaginal cells. In the present study, 212 strains, isolated from urine of 212 infected patients, were tested for adhesion by using an in vitro human cell line assay. A variable degree of attachment to the cell monolayer was detected in these strains. From patients with cystitis, only 19 (9.7%) of the 195 strains examined were adherent, whereas 5 (29.4%) of the 17 pyelonephritis strains had similar properties (P less than 0.05). To investigate the incidence of adhesion in the clinical manifestations of urinary tract infection, a sample of patients was picked at random from those with cystitis. During cystitis caused by adhesive bacteria, patients suffer more often from macroscopic hematuria than from dysuria, frequency, or recurrency (P less than 0.05). This study shows that E. coli strains isolated from urine samples possess a strikingly difference in capacity to adhere to a human cell line surface as demonstrated previously with uroepithelial or vaginal cells. Moreover, according to these data, the adhesion of E. coli may be considered as a virulent factor and would play a part in the infection of the urinary tract in humans.

The O-antigen types of 600 independently isolated Escherichia coli strains from human feces have been determined, and the types have been related to the antibiotic resistance patterns of the strains. The relative abundance of each O-antigen type differed in the susceptible and resistant series of strains. The majority (86%) of the resistant strains carried R plasmids. Resistant E. coli (20.3%) were found associated with O-antigen types 8, 9 and 101, whereas the susceptible strains covered a wide range of O-antigen types. Examination of 174 resistant strains isolated from calf feces also showed a prevalence of O-antigen types 8, 9, 101 (24.1%), and it seems probable that strains expressing these three O-antigen types commonly carry R plasmids in the alimentary tracts of man and calves. The number of strains not typeable with the O sera available were similar in the human (12.5%) and the calf (11.5%) series. There are no grounds for distinguishing "human" from "calf" E. coli on the basis of their O-antigen reactions.