There is some evidence to suggest that microbial growth inhibition may occur in chronic abscesses. A substance perhaps responsible for this phenomenon is calprotectin, a neutrophil cytoplasmic protein that inhibits microbial growth and that belongs to a class of proteins often having specific binding sites for zinc. In the present study, the suppressive effects of either human or mouse neutrophil lysates on Candida albicans growth were found to be completely reversed by micromolar quantities of zinc but not by iron or other trace elements. Similarly, supernatants of exudates from experimental abscesses in mice or from clinical specimens of abscesses in humans markedly inhibited the proliferation of C. albicans, and this effect was also completely reversed by zinc. A protein complex characteristic of calprotectin was identified in the abscess fluids. Preparations of the neutrophil growth-inhibiting protein, containing predominantly calprotectin, were shown to have zinc-binding activity by a dialysis technique. These findings suggest that the major mechanism of C. albicans growth inhibition by abscess fluids is through competition for zinc by a cytoplasmic protein apparently released from dying neutrophils.

Studies of experimental infections in animals indicate that phagocytic cells may sometimes control infective foci without actually ingesting or contacting the invading microorganisms. In the present study, an effective inhibitor of Candida albicans growth, previously detected in neutrophils cytoplasm and found to be released only after lysis of the cells, was identified as an abundant calcium-binding protein originally described in neutrophils as the L1 myelomonocytic antigen or the cystic fibrosis antigen. This substance was demonstrated also to have static activity against several other important human pathogens, including Aspergillus fumigatus, Staphylococcus aureus, and Escherichia coli. Growth of the various microorganisms was inhibited to considerably different degrees by the neutrophil protein, with the effects on S. aureus (the least responsive organism) being significantly enhance by addition of calcium to the medium. These findings suggest that after its release by the death of neutrophils at sites of tissue infection, this abundant calcium-binding protein could have a host defense function by controlling the growth of pathogenic microorganisms that escape being killed initially and would otherwise be free to proliferate.

No abstract

The adherence and inhibition of adherence of Candida albicans to epithelial cells was studied for human cells obtained from skin (corneocytes) and buccal mucosa. The yeast adhered to both kinds of cells, although in somewhat greater numbers to buccal mucosal cells. Adherence to the cells of different individuals was variable, but the ratios of values for the two kinds of cells from a single subject were quite constant. Inhibition of adherence was produced by several sugars, including the aminosugars mannosamine, glucosamine, and galactosamine. The pattern of inhibition produced by the sugars was similar for the two types of cells. Pretreatment of the yeast with mannosamine, followed by dilution to a subinhibitory concentration, produced some inhibition of yeast-buccal mucosal cell attachment, indicating some direct interaction between the sugar and the fungal cell. These data suggest that the mechanisms whereby C. albicans attaches to corneocytes and to buccal mucosal cells are probably similar. Candida albicans is a human pathogen that can cause serious infections of deep tissues or superficial infections of skin and mucous membranes. This organism is frequently

In lymphocyte transformation studies using optimal concentrations of P. orbiculare and C. albicans extracts, positive responses were found in 31 of 32 normal human subjects to the former and 44 of 49 to the latter. The overall degree of sensitivity to extracts of the 2 organisms as judged by stimulation ratios was not significantly different. The organisms did not appear to cross-react in lymphocyte transformation tests, and in individual human subjects tested with both organisms, a strong response to one did not correlate with a strong response to the other. Extracts of neither organism contained substances suppressive of lymphocyte transformation. P. orbiculare extracts appeared to be significantly less antigenic than those of C. albicans, whether tested against naturally-sensitized humans or artificially-sensitized guinea pigs even though the same amount of protein was extractable from each organism. Therefore, these studies indicate that P. orbiculare has been as successful as C. albicans in producing sensitization against its antigens in the general human population. However, P. orbiculare appears to be significantly less antigenic than is C. albicans, a finding which might be related to the relative lack of inflammation in lesions produced by P. orbiculare, and the rather high incidence of chronic tinea versicolor as compared to chronic mucocutaneous candidiasis.