Moser S A, Koker P J, Williams J E
Department of Pathology, Jewish Hospital, Saint Louis, Missouri 63110.
Infect Immun. 1988 Jan;56(1):34-9. doi: 10.1128/iai.56.1.34-39.1988.
Intratracheal injection of 10(4) conidia of Blastomyces dermatitidis strain M1-A into mice was shown in previous work to induce chronic pulmonary and disseminated infection with histopathologic features of chronic human blastomycosis. Furthermore, 10-fold variations in inoculum density produced marked changes in mean survival times (MSTs), i.e., 32 days at 10(6), 36 days at 10(5), 97 days at 10(4), and 172 days at 10(3). A second strain (M1-B) failed to induce death in this model. To assess fungal-strain-dependent virulence, we extended these previous studies to 11 additional human isolates. Groups of male BALB/cByJ mice (6 to 8 weeks old) were injected intratracheally with 10(4) conidia from each of the 13 strains; the mice were weighed weekly and monitored for mortality, and their lungs were examined histopathologically. Infection rate and mortality were 100% in all groups except for the M1-B inoculated mice. For strains M1-B and M1-A, MST and mortality curves were not significantly different from those observed in our previously reported experiments. Four different survival patterns were noted in infected mice. The shortest MSTs were produced by strains M2-E, M2-B, M2-K, M2-H, and M2-A (24, 26, 26, 27, and 31 days, respectively), and the longest MST was seen in animal groups inoculated with strains M2-J and M2-G (130 and 134 days, respectively). Strains M2-I, M2-F, and M2-D produced intermediate MSTs of 65, 79, and 80 days, respectively. The 107-day MST induced by M1-A did not differ from strain M2-C-induced MST but differed significantly from the MST produced by the other strains. Pulmonary histopathology was similar in all animals dying with blastomycosis. The wide spectrum in survival times was not related to differences in clinical status of the patient from whom the isolate had been obtained, to fungal inoculum viability, or to individual mouse weight at inoculation. Strain-dependent virulence factors present in these fungal isolates alter the disease course in inbred mice in a fashion similar to that induced by 10-fold inoculum variation of strain M1-A conidia. These 13 isolates of B. dermatitidis, 1 avirulent and 12 with differing levels of virulence, provide tools for future studies into the nature of fungal virulence determinants in chronic blastomycosis.
先前的研究表明，向小鼠气管内注射10⁴ 皮炎芽生菌菌株M1-A的分生孢子可诱发慢性肺部感染和播散性感染，其组织病理学特征与人类慢性芽生菌病相似。此外，接种密度10倍的变化会使平均存活时间（MST）产生显著变化，即接种10⁶ 时为32天，接种10⁵ 时为36天，接种10⁴ 时为97天，接种10³ 时为172天。在该模型中，第二个菌株（M1-B）未能导致小鼠死亡。为了评估真菌菌株依赖性毒力，我们将这些先前的研究扩展到另外11株人类分离株。将雄性BALB/cByJ小鼠（6至8周龄）分组，经气管内注射来自这13个菌株的10⁴ 分生孢子；每周称小鼠体重并监测死亡率，对其肺部进行组织病理学检查。除接种M1-B的小鼠外，所有组的感染率和死亡率均为100%。对于菌株M1-B和M1-A，MST和死亡率曲线与我们先前报道的实验中观察到的无显著差异。在感染的小鼠中观察到四种不同的存活模式。存活时间最短的是菌株M2-E、M2-B、M2-K、M2-H和M2-A（分别为24、26、26、27和31天），存活时间最长的是接种菌株M2-J和M2-G的动物组（分别为130和134天）。菌株M2-I、M2-F和M2-D产生的MST处于中间水平，分别为65、79和80天。M1-A诱导的107天MST与菌株M2-C诱导的MST无差异，但与其他菌株产生的MST有显著差异。所有死于芽生菌病的动物肺部组织病理学相似。存活时间的广泛差异与分离株所来自患者临床状态的差异、真菌接种物活力或接种时小鼠个体体重无关。这些真菌分离株中存在的菌株依赖性毒力因子以类似于菌株M1-A分生孢子接种量10倍变化所诱导的方式改变近交系小鼠的病程。这13株皮炎芽生菌分离株，1株无毒力，12株毒力水平不同，为未来研究慢性芽生菌病中真菌毒力决定因素的性质提供了工具。
