Texas A&M University, College of Veterinary Medicine and Biomedical Sciences, Department of Veterinary Pathobiology, College Station, Texas, United States of America.
Texas A&M University, Health Science Center and College of Medicine, Department of Microbial Pathogenesis and Immunology, College Station, Texas, United States of America.
PLoS One. 2019 Mar 5;14(3):e0212457. doi: 10.1371/journal.pone.0212457. eCollection 2019.
B. melitensis is considered the most virulent of the Brucella species, and a need exists for an improved laboratory animal model of infection that mimics natural transmission and disease. Guinea pigs are highly susceptible to infection with Brucella spp. and develop a disease syndrome that mimics natural disease after aerosol inoculation. Intratracheal inoculation is a targeted means of generating aerosols that offer advantages over aerosol chamber delivery. To establish this delivery method, female, Hartley guinea pigs were infected via intratracheal inoculation with PBS or 16M B. melitensis at low dose (101 to 103) or high dose (106 to 108) and monitored for 30 days for signs of disease. Guinea pigs in the high dose groups developed fever between 12-17 days post-inoculation. Bacteria were recovered from the spleen, liver, lymph nodes, lung, and uterus at 30-days post-inoculation and demonstrated dose dependent mean increases in colonization and pathologic changes consistent with human brucellosis. To study the kinetics of extrapulmonary dissemination, guinea pigs were inoculated with 107 CFU and euthanized at 2-hours post inoculation and at weekly intervals for 3 weeks. 5.8x105 to 4.2x106 CFU were recovered from the lung 2 hours post-inoculation indicating intratracheal inoculation is an efficient means of infecting guinea pigs. Starting at 1-week post inoculation bacteria were recovered from the aforementioned organs with time dependent mean increases in colonization. This data demonstrates that guinea pigs develop a disease syndrome that models the human manifestation of brucellosis, which makes the guinea pig a valuable model for pathogenesis studies.
B 型马耳他布鲁氏菌被认为是布鲁氏菌属中最具毒力的一种，因此需要建立一种能够模拟自然传播和疾病的改良感染实验动物模型。豚鼠极易感染布鲁氏菌属，且在气溶胶接种后会产生类似于自然疾病的疾病综合征。气管内接种是一种产生气溶胶的靶向手段，与气溶胶室输送相比具有优势。为了建立这种输送方法，雌性 Hartley 豚鼠通过气管内接种 PBS 或低剂量（101 至 103）或高剂量（106 至 108）的 16M B. melitensis 进行感染，并在 30 天内监测疾病迹象。高剂量组的豚鼠在接种后 12-17 天内出现发热。在接种后 30 天从脾、肝、淋巴结、肺和子宫中回收细菌，并显示出与人类布鲁氏菌病一致的剂量依赖性定植和病理变化增加。为了研究肺外传播的动力学，豚鼠接种 107 CFU，并在接种后 2 小时和每周间隔 3 周时安乐死。在接种后 2 小时从肺中回收了 5.8x105 至 4.2x106 CFU，表明气管内接种是一种有效的感染豚鼠的方法。从接种后 1 周开始，从上述器官中回收细菌，定植呈时间依赖性增加。该数据表明，豚鼠会产生类似于人类布鲁氏菌病的疾病综合征，这使得豚鼠成为发病机制研究的有价值模型。
