We have identified verotoxin 1 (VT1) as the active component within an antineoplastic bacteriocin preparation from Escherichia coli HSC10 studied over two decades. Recombinant VT1 can simulate the toxicity of anticancer proteins (ACP), and the antineoplastic activity of ACP (and VT1) was abrogated by treatment with anti-VTI antibody. Similarly, VT1 mimics the protective effect ofACP in a murine metastatic fibrosarcoma model. Prior immunization with VT1 B subunit prevents the effect ofVT1 or ACP in this model. The activity of ACP against a variety of human ovarian cell lines was mimicked by VT1, and multidrug-resistant variants were significantly hypersensitive. Primary ovarian tumors and metastases contain elevated levels of globotriaosylceramide compared with normal ovaries, and overlay of frozen tumor sections showed selective VT binding to tumor tissue and the lumen of invading blood vessels. Our contention that VT1 could provide an additional approach to the management of certain human neoplasms is discussed.Bacteriocins are bacterial proteins produced to prevent the growth of competing microorganisms in a particular biological niche. A preparation of bacteriocin from a strain ofEscherichia coli (HSC1o) has long been shown to have antineoplastic activity against a variety of human tumor cell lines in vitro (1-3) and more recently against Mycosis fungoides skin tumors in man (R. Schachter, personal communication). This preparation of partially purified bacteriocin (PPB) or anticancer proteins (ACP) (3) was also effective in a murine sarcoma tumor model to prevent metastases to the lung from an intravenous injection (3).We now demonstrate that verotoxin 1 (VT1) is the active component within the ACP preparation and that purified VT1 has a potent antineoplastic effect in vitro and in vivo.
Coagulase-negative pathogenic staphylococci were studied physiologically and serologically to determine their relationship to Staphylococcus aureus. When 46 characters were studied and tallied, the 21 coagulase-negative pathogenic strains made up a heterogeneous intermediate group sharing not all the characters of S. aureus but appreciably more than S. epidermidis. Some characters among the coagulase-negative pathogens indicating a relationship to S. aureus were serotyping, lysostaphin sensitivity, growth rates, and endogenous respiration. Seventy-one percent of the coagulase-negative pathogenic strains were resistant to penicillin; of these, 80% were multiple antibiotic resistant.From these results it would appear that the genus Staphylococcus cannot be divided satisfactorily into demarcated species but that strains within this genus form a continuous spectrum between the two presently recognizable extremes with new subtypes evolving as characters are lost. If a species must be designated under the existing system of classification, a strain producing coagulase can be called S. aureus. However, coagulase-negative pathogenic strains cannot be classified with accuracy as S. epidermidis on the basis of the absence of this single character, coagulase.
FARKAS-HIMSLEY, H. (Hebrew University-Hadassah Medical School, Jerusalem, Israel). Killing of chlorine-resistant bacteria by chlorine-bromine solutions. Appl. Microbiol. 12:1-6. 1964.-The disinfective power of chlorine, bromine, and mixtures of chlorine and bromine at different ratios was compared. The influence of pH was also studied. The experiments were carried out in "purified" water and in natural waters of swimming pools, river, and sea. In the presence of high amounts of nitrogenous growth-promoting material (at neutral pH), bromine was more effective than chlorine; in waters containing low amounts of nitrogenous growth-promoting material, chlorine was found superior. Mixtures of chlorine and bromine at various ratios were found to increase in effectiveness inversely to the percentage of hypobromite generated, down to 10 or 5%. Such effectiveness was found at pH levels of 5.4 to 8.6 in both purified and natural water containing high and low amounts of nitrogenous growth-promoting material. Therefore, the above mixtures seem of practical value for the disinfection of various natural waters. Escherichia coli isolated in the presence of chlorine, either from swimming pools or after deliberate exposure to the halogen, were shown to be chlorine-resistant mutants. Their resistance was maintained for at least nine passages in the absence of the disinfectant, which accounts for the number of passages tested. Chlorine-resistant mutants were not affected by bromine alone but did show a marked sensitivity to low concentrations of bromine active in the presence of chlorine. This was achieved by admixing small amounts of bromide to hypochlorite. A hypothetical model is presented to explain the synergistic sequential block by the two disinfectants. Some chlorine-resistant mutants were found to have changed into relatively slowgrowing organisms with a changed phage-sensitivity pattern. Chlorine (C12) or bromine (Br2) are widely used in the sterilization of water. It was known that hypochlorite reinforced by bromide has a superior effect in bleaching cellulosic fibers to hypochlorite used alone (Bloch et al., 1949). The advantage in the combined effect of both halogens was attributed to the continuous generation of hypobromite by oxidation of bromides with hypochlorite as long as hypochlorite is in excess (Farkas, Lewin, and Bloch, 1949). C10-+ Br-* BrO-+ Cl-BrO-+ organic substrate > Br-+ organic substrate (oxidized)
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