Abstract
Previous experiments indicated that MIF-A3, a peptidoglycolipid extracted from Mycobacterium avium serovar 2 (Mycobacterium paratuberculosis 18), inhibits the killing of Candida albicans by activated bovine peripheral blood derived macrophages and murine thioglycollate-elicited peritoneal macrophages in vitro. Subsequent in vitro data from our laboratory indicated that this reduction in killing may be related to the ability of MIF-A3 to scavenge reactive oxygen species (ROS). In this study we examined this hypothesis directly by determining if MIF-A3 reduced exogenous H2O2- induced candidacidal activity. When Candida albicans was incubated with H2O2 (4 mM) alone, colony-forming units/ml x 104 (CFU/ml) were 0.4 ± 0.1 (mean ± SE, n = 4) as compared to 11.3 ± 2.0 CFU/ml in control (untreated) cultures (p < .05). The addition of catalase at concentrations ≤ 6.8 U/ml, completely blocked the fungicidal effect of H2O2. However, reducing the amount of catalase from 6.8 U/ml to 3.4 U/ml resulted in a loss of scavenging activity, which was associated with a 50% increase in H2O2-mediated killing. Substituting MIF-A3 (400 μg/ml) for catalase, also reduced H2O2- induced fungicidal activity. In the absence of MIF-A3, H2O2 reduced Candida albicans to less than 103 CFU/ml. However, in the presence of MIF-A3 the CFU/ml of Candida albicans increased 7.5-fold. Based on concentration response curves of H2O2 inhibition vs. increasing amounts of catalase we determined that the relative inhibitory capacity of the MIF-A3 (400 μg/ml) was ~1.0 U/ml 'catalase equivalents.' These findings provide direct evidence that MIF-A3 can scavenge H2O2, and reduce H2O2-induced killing of Candida albicans.
Original language | English (US) |
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Pages (from-to) | 561-565 |
Number of pages | 5 |
Journal | Free Radical Biology and Medicine |
Volume | 22 |
Issue number | 3 |
DOIs | |
State | Published - 1997 |
Externally published | Yes |
Keywords
- Free radicals
- Host defense
- Killing of Candida albicans
- Mycobacteria
- Reactive oxygen species
ASJC Scopus subject areas
- Medicine(all)
- Toxicology
- Clinical Biochemistry