Sugar A M, Chahal R S, Brummer E, Stevens D A
Infect Immun. 1983 Sep;41(3):908-12. doi: 10.1128/iai.41.3.908-912.1983.
Three strains of Blastomyces dermatitidis which differ in their virulence for mice were exposed in their yeast form to various components of the peroxidase-hydrogen peroxide-halide system. Susceptibility to H2O2 alone correlated with virulence, with the most virulent strain (ATCC 26199) least susceptible (50% lethal dose, greater than 50 mM) and an avirulent strain (ATCC 26197) most susceptible (50% lethal dose less than 3.3 mM). A strain of intermediate virulence (ATCC 26198) was of intermediate susceptibility (50% lethal dose, 11.5 mM). The addition of a nontoxic concentration of KI (5 X 10(-4) M) did not increase H2O2 toxicity. However, the addition of either myeloperoxidase or horseradish peroxidase and KI markedly decreased the amount of H2O2 required to kill the organisms, with 100 +/- 0% of all strains killed at 5 X 10(-5) M H2O2 and 97 +/- 4, 100 +/- 0, and 94 +/- 8% of ATCC 26199, ATCC 26198, and ATCC 26197 killed, respectively, at 5 X 10(-6) M H2O2. Kinetic studies with H2O2 alone revealed a delayed onset of killing, but virtually 100% of organisms were killed by 120 min of exposure in all strains. By comparison, the peroxidase-hydrogen peroxide-halide system was 100% lethal for all strains at 1 min. The relatively high concentrations of H2O2 required to kill the yeast phase of B. dermatitidis suggest that H2O2 alone does not account for host resistance to the organism. However, the rapidly lethal effect of the peroxidase-hydrogen peroxide-halide system at physiologically relevant concentrations suggests that this may be one mechanism of host defense to B. dermatitidis.
将三株对小鼠毒力不同的皮炎芽生菌以酵母形式暴露于过氧化物酶 - 过氧化氢 - 卤化物系统的各种成分中。单独对H2O2的敏感性与毒力相关，最具毒力的菌株（ATCC 26199）最不敏感（半数致死剂量，大于50 mM），无毒力菌株（ATCC 26197）最敏感（半数致死剂量小于3.3 mM）。中等毒力的菌株（ATCC 26198）敏感性居中（半数致死剂量，11.5 mM）。添加无毒浓度的KI（5×10⁻⁴ M）不会增加H2O2的毒性。然而，添加髓过氧化物酶或辣根过氧化物酶以及KI会显著降低杀死这些微生物所需的H2O2量，在5×10⁻⁵ M H2O2时所有菌株的杀灭率为100±0%，在5×10⁻⁶ M H2O2时，ATCC 26199、ATCC 26198和ATCC 26197的杀灭率分别为97±4%、100±0%和94±8%。单独用H2O2进行的动力学研究显示杀灭作用起效延迟，但在所有菌株中，暴露120分钟后几乎100%的微生物被杀死。相比之下，过氧化物酶 - 过氧化氢 - 卤化物系统在1分钟时对所有菌株的致死率为100%。杀死皮炎芽生菌酵母相所需的相对高浓度的H2O2表明，仅H2O2并不能解释宿主对该微生物的抵抗力。然而，过氧化物酶 - 过氧化氢 - 卤化物系统在生理相关浓度下的快速致死作用表明，这可能是宿主防御皮炎芽生菌的一种机制。
