Center for Microbial Pathogenesis, Research Institute at Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH 43205, USA.
Microbes Infect. 2011 May;13(5):426-37. doi: 10.1016/j.micinf.2010.12.004. Epub 2010 Dec 21.
Uropathogenic Escherichia coli proceed through a complex intracellular developmental pathway that includes multiple morphological changes. During intracellular growth within Toll-like receptor 4-activated superficial bladder epithelial cells, a subpopulation of uropathogenic E. coli initiates SulA-mediated filamentation. In this study, we directly investigated the role of bacterial morphology in the survival of uropathogenic E. coli from killing by phagocytes. We initially determined that both polymorphonuclear neutrophils and macrophages are recruited to murine bladder epithelium at times coincident with extracellular bacillary and filamentous uropathogenic E. coli. We further determined that bacillary uropathogenic E. coli were preferentially destroyed when mixed uropathogenic E. coli populations were challenged with cultured murine macrophages in vitro. Consistent with studies using elliptical-shaped polymers, the initial point of contact between the phagocyte and filamentous uropathogenic E. coli influenced the efficacy of internalization. These findings demonstrate that filamentous morphology provides a selective advantage for uropathogenic E. coli evasion of killing by phagocytes and defines a mechanism for the essential role for SulA during bacterial cystitis. Thus, morphological plasticity can be viewed as a distinct class of mechanism used by bacterial pathogens to subvert host immunity.
尿路致病性大肠杆菌经历一个复杂的细胞内发育途径，包括多种形态变化。在 Toll 样受体 4 激活的膀胱表面上皮细胞内的细胞内生长过程中，尿路致病性大肠杆菌的一个亚群开始 SulA 介导的丝状化。在这项研究中，我们直接研究了细菌形态在逃避吞噬细胞杀伤方面对尿路致病性大肠杆菌存活的作用。我们最初确定，嗜中性粒细胞和巨噬细胞在与体外杆菌和丝状尿路致病性大肠杆菌一致的时间被募集到小鼠膀胱上皮。我们进一步确定，当混合尿路致病性大肠杆菌群体在体外受到培养的小鼠巨噬细胞挑战时，杆菌尿路致病性大肠杆菌优先被破坏。与使用椭圆形聚合物的研究一致，吞噬细胞和丝状尿路致病性大肠杆菌之间的初始接触点影响内化的效果。这些发现表明，丝状形态为尿路致病性大肠杆菌逃避吞噬细胞杀伤提供了选择性优势，并定义了 SulA 在细菌性膀胱炎中的重要作用的机制。因此，形态可塑性可以被视为细菌病原体颠覆宿主免疫的一个独特的机制类别。
