Non-invasive monitoring of Streptococcus pyogenes vaccine efficacy using biophotonic imaging.
Non-invasive monitoring of Streptococcus pyogenes vaccine efficacy using biophotonic imaging.
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DOI：
10.1371/journal.pone.0082123
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Sriskandan S
中科院分区：
文献类型：
--
作者：
Alam FM;Bateman C;Turner CE;Wiles S;Sriskandan S
化脓性链球菌感染鼻咽代表了该生物体致病循环中的关键步骤，也是疫苗开发的主要焦点，需要稳健的模型来促进潜在保护性抗原的筛选。可能是疫苗接种的重要靶标的一种抗原是趋化因子蛋白酶SpyCEP，其与细胞表面相关并在发病机制中起作用。生物光子成像（BPI）可以非侵入性地表征体内发光细菌的空间位置和丰度。我们已经开发了一种咽部S的生物发光衍生物。通过用luxABCDE操纵子转化emm75临床分离株来转化化脓性链球菌菌株。在体外和体内的同基因重组菌株的评价证实，生物发光赋予的生长缺陷，表现为在感染过程中的健身成本。尽管如此，生物发光表达允许无创纵向定量S。尽管在该区域中的检测限对应于约105个细菌菌落形成单位（CFU），但是在小鼠鼻咽内的化脓性链球菌中检测到细菌。用热杀死的链球菌或SpyCEP接种小鼠会在血清中产生特异性IgG反应。BPI证明，两种候选疫苗都减少了S。化脓性链球菌在鼻咽感染过程中的生物发光发射。这项工作表明，潜在的BPI用于无创纵向评估潜在S。化脓性疫苗。
Streptococcus pyogenes infection of the nasopharynx represents a key step in the pathogenic cycle of this organism and a major focus for vaccine development, requiring robust models to facilitate the screening of potentially protective antigens. One antigen that may be an important target for vaccination is the chemokine protease, SpyCEP, which is cell surface-associated and plays a role in pathogenesis. Biophotonic imaging (BPI) can non-invasively characterize the spatial location and abundance of bioluminescent bacteria in vivo. We have developed a bioluminescent derivative of a pharyngeal S. pyogenes strain by transformation of an emm75 clinical isolate with the luxABCDE operon. Evaluation of isogenic recombinant strains in vitro and in vivo confirmed that bioluminescence conferred a growth deficit that manifests as a fitness cost during infection. Notwithstanding this, bioluminescence expression permitted non-invasive longitudinal quantitation of S. pyogenes within the murine nasopharynx albeit with a detection limit corresponding to approximately 105 bacterial colony forming units (CFU) in this region. Vaccination of mice with heat killed streptococci, or with SpyCEP led to a specific IgG response in the serum. BPI demonstrated that both vaccine candidates reduced S. pyogenes bioluminescence emission over the course of nasopharyngeal infection. The work suggests the potential for BPI to be used in the non-invasive longitudinal evaluation of potential S. pyogenes vaccines.
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