Conover Matt S, Flores-Mireles Ana L, Hibbing Michael E, Dodson Karen, Hultgren Scott J
Department of Molecular Microbiology and Center for Women's Infectious Disease Research, Washington University School of Medicine;
Department of Molecular Microbiology and Center for Women's Infectious Disease Research, Washington University School of Medicine.
J Vis Exp. 2015 Jun 23(100):e52892. doi: 10.3791/52892.
Urinary tract infections (UTI) are highly prevalent, a significant cause of morbidity and are increasingly resistant to treatment with antibiotics. Females are disproportionately afflicted by UTI: 50% of all women will have a UTI in their lifetime. Additionally, 20-40% of these women who have an initial UTI will suffer a recurrence with some suffering frequent recurrences with serious deterioration in the quality of life, pain and discomfort, disruption of daily activities, increased healthcare costs, and few treatment options other than long-term antibiotic prophylaxis. Uropathogenic Escherichia coli (UPEC) is the primary causative agent of community acquired UTI. Catheter-associated UTI (CAUTI) is the most common hospital acquired infection accounting for a million occurrences in the US annually and dramatic healthcare costs. While UPEC is also the primary cause of CAUTI, other causative agents are of increased significance including Enterococcus faecalis. Here we utilize two well-established mouse models that recapitulate many of the clinical characteristics of these human diseases. For UTI, a C3H/HeN model recapitulates many of the features of UPEC virulence observed in humans including host responses, IBC formation and filamentation. For CAUTI, a model using C57BL/6 mice, which retain catheter bladder implants, has been shown to be susceptible to E. faecalis bladder infection. These representative models are being used to gain striking new insights into the pathogenesis of UTI disease, which is leading to the development of novel therapeutics and management or prevention strategies.
尿路感染(UTI)非常普遍,是发病的一个重要原因,并且对抗生素治疗的耐药性日益增强。女性受UTI影响的比例过高:所有女性中有50%在一生中会患UTI。此外,这些首次患UTI的女性中有20 - 40%会复发,一些人频繁复发,生活质量严重下降,伴有疼痛和不适,日常活动受到干扰,医疗费用增加,除了长期抗生素预防外几乎没有其他治疗选择。尿路致病性大肠杆菌(UPEC)是社区获得性UTI的主要病原体。导尿管相关尿路感染(CAUTI)是最常见的医院获得性感染,在美国每年发生一百万例,造成巨大的医疗费用。虽然UPEC也是CAUTI的主要原因,但其他病原体的重要性也在增加,包括粪肠球菌。在这里我们利用两种成熟的小鼠模型,它们概括了这些人类疾病的许多临床特征。对于UTI,C3H/HeN模型概括了在人类中观察到的UPEC毒力的许多特征,包括宿主反应、IBC形成和丝状化。对于CAUTI,使用保留导尿管膀胱植入物的C57BL/6小鼠的模型已被证明易患粪肠球菌膀胱感染。这些具有代表性的模型正在被用于对UTI疾病的发病机制获得惊人的新见解,这正导致新疗法以及管理或预防策略的开发。