Department of Medical Microbiology and Infectious Diseases, Erasmus MC, Rotterdam, The Netherlands.
Animal Science Department, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
PLoS One. 2018 Apr 12;13(4):e0194718. doi: 10.1371/journal.pone.0194718. eCollection 2018.
Our human model of nasal colonization and eradication of S. aureus is limited by safety issues. As rhesus macaques are closely related to humans and natural hosts for S. aureus, we developed an experimental decolonization and inoculation protocol in these animals. Animals were screened for nasal carriage of S. aureus and 20 carriers were selected. Decolonization was attempted using nasal mupirocin (10 animals) or mupirocin plus trimethoprim/sulfadiazine intramuscularly (10 animals) both once daily for 5 days, and checked by follow-up cultures for 10 weeks. Intranasal inoculation was performed with S. aureus strain 8325-4 in culture-negative animals. 11/20 animals, of which 5 received mupirocin and 6 the combination treatment, became culture-negative for S. aureus for 10 weeks and these 11 animals were subsequently inoculated. Swabs were taken once a week for 5 weeks to test for the presence of the inoculated strain. In 3 animals, strain 8325-4 was cultured from the nose 1 week after inoculation, indicating short-term survival of this strain only, a finding similar to that previously found in our human model. These data demonstrate that rhesus macaques may constitute a relevant animal model to perform S. aureus eradication and inoculation studies with relatively limited invasive handling of the animals.
我们用于鼻腔定植和根除金黄色葡萄球菌的人体模型受到安全性问题的限制。由于恒河猴与人密切相关,且是金黄色葡萄球菌的天然宿主,因此我们在这些动物中开发了一种实验性的去定植和接种方案。动物经筛选确定为鼻腔携带金黄色葡萄球菌,然后选择 20 名携带菌者。定植菌采用鼻腔涂抹莫匹罗星(10 只动物)或莫匹罗星联合肌肉注射甲氧苄啶/磺胺甲噁唑(10 只动物),每天 1 次,连续 5 天,通过后续培养检查 10 周。对培养阴性的动物进行培养的金黄色葡萄球菌菌株 8325-4 鼻腔接种。20 只动物中有 11 只(5 只接受莫匹罗星治疗,6 只接受联合治疗)在 10 周内培养出金黄色葡萄球菌,这 11 只动物随后进行了接种。在接种后 5 周内每周采集一次拭子,以检测接种菌株的存在。在 3 只动物中,接种后 1 周从鼻子中培养出了 8325-4 株,这表明该菌株只能短期存活,这一发现与我们在人体模型中发现的情况相似。这些数据表明,恒河猴可能构成一个相关的动物模型,可用于进行金黄色葡萄球菌根除和接种研究,对动物的侵入性处理相对较少。