Effect of proteolytic activity on virulence of Candida albicans in burned mice

Abstract

Total circulating proteolytic activity (PA) was determined by measuring the acid-soluble 125I-protein fragments generated per 100 microliters of serum incubated with 125I-protein at 37 degrees C for 15 min. Normal mice had low circulating PA (1.3 +/- 0.2 micrograms/100 microliters), and burned mice had a higher average PA; the actual value depended on the time of measurement postburn. We measured the effect on mortality and on circulating PA of challenging normal and burned mice with high-virulence strain Candida albicans MY 1044 and its less virulent mutant MY 1049. Burned and normal mice challenged with a high dose (10(5)) of MY 1044 had high mortality (greater than 90%) and high circulating PA (greater than 33 micrograms generated per 100 microliters). Burned mice challenged with a lower dose (10(4] of MY 1044 had moderate mortality (63%) and lower PA (27.2 +/- 4.2 micrograms/100 microliters). All other groups of mice, including burned mice challenged with 10(5) MY 1049, had low mortality (less than 10%), and PAs were less than 22 micrograms/100 microliters. Augmentation of burned mice challenged with 10(5) MY 1049 with proteinase significantly increased mortality; with treatment of burned mice challenged with 10(5) MY 1044 with proteinase inhibitor significantly decreased mortality. We conclude that mortality correlated with total circulating PA; that the contribution to this net PA was the background PA level in the normal mice, the PA associated with the burn, and the PA caused by infection with a C. albicans strain with a particular virulence; that most deaths caused by C. albicans occurred past a PA threshold of 25 micrograms/100 microliters in the host; and that the number of burned and infected mice that died of candidiasis could be modulated by the addition of proteinases or proteinase inhibitors to the host. This last finding may lead to some novel treatments for candidiasis in burned hosts.