Simpson Morgan, Bilverstone Terry, Leslie Jhansi, Donlan Alexandra, Uddin Md Jashim, Petri William A, Marin Natasha, Kuehne Sarah, Minton Nigel P, Petri William A
Department of Pathology, University of Virginia, Charlottesville, Virginia, USA.
BBSRC/EPSRC Synthetic Biology Research Centre (SBRC), School of Life Sciences, Centre for Biomolecular Sciences, The University of Nottingham, Nottingham, United Kingdom.
Open Forum Infect Dis. 2023 Jan 31;10(3):ofad040. doi: 10.1093/ofid/ofad040. eCollection 2023 Mar.
is the leading cause of hospital-acquired gastrointestinal infection, in part due to the existence of binary toxin (CDT)-expressing hypervirulent strains. Although the effects of the CDT holotoxin on disease pathogenesis have been previously studied, we sought to investigate the role of the individual components of CDT during in vivo infection.
To determine the contribution of the separate components of CDT during infection, we developed strains of expressing either CDTa or CDTb individually. We then infected both mice and hamsters with these novel mutant strains and monitored them for development of severe illness.
Although expression of CDTb without CDTa did not induce significant disease in a mouse model of infection, we found that complementation of a CDT-deficient strain with CDTb alone restored virulence in a hamster model of infection.
Overall, this study demonstrates that the binding component of binary toxin, CDTb, contributes to virulence in a hamster model of infection.
是医院获得性胃肠道感染的主要原因,部分原因是存在表达二元毒素(CDT)的高毒力菌株。尽管先前已经研究了CDT全毒素对疾病发病机制的影响,但我们试图研究CDT各个组分在体内感染过程中的作用。
为了确定CDT各单独组分在感染过程中的作用,我们构建了分别单独表达CDTa或CDTb的菌株。然后用这些新型突变菌株感染小鼠和仓鼠,并监测它们是否出现严重疾病。
尽管在感染的小鼠模型中,单独表达CDTb而不表达CDTa不会引发明显疾病,但我们发现,在感染的仓鼠模型中,仅用CDTb对缺乏CDT的菌株进行互补可恢复其毒力。
总体而言,本研究表明,二元毒素的结合组分CDTb在仓鼠感染模型中对毒力有影响。