Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Proc Natl Acad Sci U S A. 2012 Aug 21;109(34):13823-8. doi: 10.1073/pnas.1208075109. Epub 2012 Aug 6.
Nasal colonization by Staphylococcus aureus is the major risk factor for disease and transmission. Epidemiological studies have reported a reduced risk of S. aureus carriage in immunocompetent but not in immunocompromised children colonized by Streptococcus pneumoniae. We investigate the hypothesis that the immune response to pneumococcal colonization affects S. aureus colonization. We demonstrate that pneumococcal colonization in mice inhibits subsequent S. aureus acquisition in an antibody-dependent manner and elicits antibody that cross-reacts with S. aureus. We identify the staphylococcal target of cross-reactive antibody as 1-pyrroline-5-carboxylate dehydrogenase (P5CDH), and the homologous immunogen in S. pneumoniae as SP_1119, both of which are conserved dehydrogenases. These antigens are necessary and sufficient to inhibit the acquisition of S. aureus colonization in a mouse model. Our findings demonstrate that immune-mediated cross-reactivity between S. pneumoniae and S. aureus protects against S. aureus nasal acquisition and thus reveal a paradigm for identifying protective antigens against S. aureus.
金黄色葡萄球菌（Staphylococcus aureus）鼻腔定植是疾病和传播的主要危险因素。流行病学研究报告称，在免疫功能正常但免疫功能低下的肺炎链球菌（Streptococcus pneumoniae）定植儿童中，金黄色葡萄球菌定植的风险降低。我们研究了这样一种假设，即对肺炎球菌定植的免疫反应会影响金黄色葡萄球菌定植。我们证明，在小鼠中肺炎球菌定植以抗体依赖的方式抑制随后金黄色葡萄球菌的获得，并引发与金黄色葡萄球菌发生交叉反应的抗体。我们确定了交叉反应性抗体的金黄色葡萄球菌靶标为 1-吡咯啉-5-羧酸脱氢酶（P5CDH），以及肺炎球菌中的同源免疫原 SP_1119，两者均为保守的脱氢酶。这些抗原是在小鼠模型中抑制金黄色葡萄球菌定植获得所必需且充分的。我们的研究结果表明，肺炎球菌和金黄色葡萄球菌之间的免疫介导交叉反应可预防金黄色葡萄球菌鼻腔定植，从而揭示了一种针对金黄色葡萄球菌的保护性抗原鉴定模式。
