Kellogg Stephanie L, Little Jaime L, Hoff Jessica S, Kristich Christopher J
Department of Microbiology and Immunology, Center for Infectious Disease Research, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Department of Microbiology and Immunology, Center for Infectious Disease Research, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
Antimicrob Agents Chemother. 2017 Apr 24;61(5). doi: 10.1128/AAC.02461-16. Print 2017 May.
Enterococci are serious opportunistic pathogens that are resistant to many cell wall-targeting antibiotics. The CroRS two-component signaling system responds to antibiotic-mediated cell wall stress and is critical for resistance to cell wall-targeting antibiotics in Here, we identify and characterize an orthologous two-component system found in that is functionally equivalent to the CroRS system of Deletion of in resulted in marked susceptibility to cell wall-targeting agents including cephalosporins and bacitracin, as well as moderate susceptibility to ampicillin and vancomycin. As in , exposure to bacitracin and vancomycin stimulates signaling through the CroRS system in Moreover, the CroRS system is critical in for enhanced beta-lactam resistance mediated by overexpression of Pbp5. Expression of a Pbp5 variant that confers enhanced beta-lactam resistance cannot overcome the requirement for CroRS function. Thus, the CroRS system is a conserved signaling system that responds to cell wall stress to promote intrinsic resistance to important cell wall-targeting antibiotics in clinically relevant enterococci.
肠球菌是严重的机会致病菌，对许多作用于细胞壁的抗生素具有抗性。CroRS双组分信号系统可响应抗生素介导的细胞壁应激，对于[具体物种1]中对作用于细胞壁的抗生素的抗性至关重要。在此，我们鉴定并表征了在[具体物种2]中发现的一个直系双组分系统，其功能等同于[具体物种1]的CroRS系统。在[具体物种2]中缺失[相关基因]导致对包括头孢菌素和杆菌肽在内的作用于细胞壁的药物显著敏感，以及对氨苄青霉素和万古霉素中度敏感。与[具体物种1]一样，在[具体物种2]中，接触杆菌肽和万古霉素会刺激通过CroRS系统的信号传导。此外，在[具体物种2]中，CroRS系统对于由Pbp5过表达介导的增强的β-内酰胺抗性至关重要。赋予增强的β-内酰胺抗性的Pbp5变体的表达不能克服对CroRS功能的需求。因此，CroRS系统是一个保守的信号系统，可响应细胞壁应激，以促进临床相关肠球菌对重要的作用于细胞壁的抗生素的固有抗性。
