The binding of Candida albicans yeast cells to human fibronectin (Fn), a major glycoprotein of mammalian cells, was studied using an in vitro assay. Adherence was quantitated in microtiter dishes coated with Fn to which radiolabeled yeast cells were added. Under optimum conditions of the assay, i.e., 1 mM CaCl2 and 70 micrograms Fn protein, approximately 40% of the radiolabeled yeast cells adhered to the Fn. Adherence to Fn was greater at 30 degrees C than at 4 degrees C and was greater with viable yeast cells than with heat-killed cells. Candida albicans (two strains) and C. tropicalis adhered to Fn to a greater extent than C. pseudotropicalis, C. krusei, or Saccharomyces cerevisiae. Pretreatment of C. albicans with chymotrypsin, pronase, or papain, but not pepsin, decreased adherence to Fn. Blocking experiments using mannan, sugars, or amino sugars were carried out by preabsorbing the Fn with each of the above-mentioned compounds. Candida mannan blocked adherence of C. albicans to Fn. The mannan effect was dose dependent. However, adherence of C. albicans to Fn was not significantly reduced by mannose, glucose, or several other sugars. The role of FN as a receptor for the binding of C. albicans yeast cells to buccal and vaginal epithelial cells was investigated also using an in vitro assay. We determined, using indirect fluorescent antibody techniques, that both buccal and vaginal epithelial cells possessed Fn. In addition, yeast cells, when pretreated with Fn, showed reduced adherence with buccal and vaginal cells when compared with nontreated cells. These studies may indicate a role for Fn in the adherence of C. albicans to buccal and vaginal epithelial cells.

The inhibitory effect of lipophilic acids, antimicrobial food additives, and analgesics-antipyretics was examined at concentrations from 0.1 to 100 mM in bacteria ( Bacillus subtilis and Escherichia coli ) and mammalian cells (HeLa, human fibroblasts, and mouse neuroblastoma cells). Most compounds inhibit the growth of HeLa cells about as efficiently as that of B. subtilis . However, butyrate and propionate, as well as acetaminophen, antipyrene, phenacetin, and salicylamide, inhibit HeLa at millimolar concentrations whereas, at least 10 times higher concentrations are needed to inhibit B. subtilis . The concentrations needed to inhibit growth by 50% decrease with increasing octanol-water partition coefficients of the compound. Growth of E. coli is inhibited similar to that of B. subtilis by all compounds except butylbenzoate, decanoate, and linoleate which cannot penetrate the lipopolysaccharide layer. All growth inhibitors inhibit amino acid uptake into bacteria and their vesicles, and oxygen consumption in bacteria. In HeLa cells or human fibroblasts, neither amino acid uptake nor adenine 5′-triphosphate synthesis are inhibited by fatty acids at concentrations that completely inhibit growth. Short chain fatty acids (propionate, butyrate, and pentanoate) induce in HeLa the formation of cell processes. In neuroblastoma cells, grown in the presence of 10% fetal calf serum, butyrate also induces such processes which slowly continue to grow in length for at least 7 days; these processes differ in speed of formation, width, and cycloheximide susceptibility from the thin processes produced by serum deprivation alone.

Human (BIeLa, Chang liver, L-132, and Intestine 407) and other mammalian (XC, SV3T3, and chick-embryo) cells in tissue culture are at least as sensitive to inhibition by lipophilic acids and nitrite as bacteria. Some of these compounds are the most frequently used antimicrobial food additives. Short-chain fatty acids (up to hexanoate) and parabens induce, at partially inhibitory concentrations, a jagged cell shape in continuous epithelial-like cell lines, such as HeLa, Chang liver, L-132, and Intestine 407. This morphological effect is not mediated or enhanced by butyryl cyclic AMP, which specifically affects fibroblasts.Fatty acids and other lipophilic acids, some of which are used as antimicrobial food additives, inhibit the growth of Bacillus subtilis and the uptake of amino and keto acids into bacterial membrane vesicles (1-3). Since these results indicated that lipophilic acids alter the properties of cell membranes, it appeared likely that they would also affect mammalian cells. This report demonstrates that they inhibit the growth of mammalian cells at least as effectively as that of bacteria. In addition, it shows that short-chain lipophilic acids induce filamentous protrusions in epithelial-like cells but not in cells with fibroblast morphology. These morphological changes are not mediated or enhanced by butyryl cyclic AMP (BucAMP), which alters the morphology of fibroblasts but not of epithelial cells (4, 5). MATERIALS AND METHODSCell Cultures. HeLa cells, strain R, were obtained from Grand Island Biological Co. (GIBCO), Grand Island, N.Y. and propagated in our laboratory. Cells of Chang liver (normal human epithelial cells), L-132 (originating from human embryonic lung), and Intestine 407 (epithelial cells originally derived from human embryonic jejunum and ileum) were bought from Flow Laboratories, Rockville, Md. XC cells (a cell line derived from a rat sarcoma induced by Rous sarcoma virus) were a gift from Dr. Janet Hartley, National Cancer Institute, Bethesda, Md. Chick-embryo cells were prepared from 9-day-old chick embryo (6). All the above cells were cultivated in 60-mm plastic petri dishes or 75-cm2 T flasks (Falcon Plastics, Los Angeles, Calif.) in Eagle's minimal essential medium (pH 7.4) containing 10% fetal-calf serum (GIBCO), 2 mM L-glutamine, 100 units/ml of penicillin, and 100 /Ag/ml of kanamycin. The medium containing all these additions will in the following be called "minimal essential medium." The cultures were grown at 370 in a humidified incubator provided with 4% CO2. Unless specified otherwise, HeLa cell cultures in 60-mm petri dishes were in- Chemicals. Stock solutions of 100 mM Na propionate and Na butyrate were prepared in minimal essential medium, while 2.5 M Na hexanoate (pH 7.0) was prepared in distilled water. 1 M solution of 'octanoic and decanoic acid, methyl-and propyl-paraben (paraben = p-hydroxybenzoic acid ester) were prepared in 99% dimethyl sulfoxide (Matheson, Coleman &-Bell, spectral grade) and diluted to the desired concentrations in minimal essential m...