Horizontal Genetic Transfer In Staphylococci

描述（由申请方提供）：耐甲氧西林葡萄球菌是全球医院感染的主要原因，通常对多种抗菌药物具有耐药性。辅助遗传元件SCCmec携带甲氧西林耐药决定簇，并被认为在主要葡萄球菌病原体金黄色葡萄球菌和葡萄球菌凝固酶阴性菌种如S.表皮普遍存在的核心基因的重组也被认为发生在这些物种中，但对葡萄球菌中重组的频率、相对大小和生物学后果知之甚少。我们的长期目标是了解遗传变异如何有助于细菌病原体的生态和进化成功。在本申请中，我们调查了水平遗传转移对葡萄球菌遗传变异的影响程度。通过对临床分离的葡萄球菌进行基于序列的分型，我们将检验S。epidermidis比S.金黄色葡萄球菌，和罕见的，大的种内重组导致杂交S。aureus克隆（Aim 1）。通过对SCCmec的遗传背景和分子特征的了解，我们将检验我们当地耐甲氧西林的S。金黄色葡萄球菌通过从相同种属的全球分离株而不是本地同源株获得SCCmec而产生（目的2）。此外，通过应用一种创新的PCR扫描工具，以不同的分离株，我们将测试的假设，穷人的特点S。具有临床重要性的金黄色葡萄球菌具有新的辅助基因（也是Aim 2）。最后，我们将研究葡萄球菌水平遗传转移的潜在生物学后果。通过伊卡基因座的分子表征，我们将检验遗传背景和SCCmec都是生物膜表型的独立预测因子的假设（目的3）。

DESCRIPTION (provided by applicant): Methicillin-resistant staphylococci are a leading cause of nosocomial infections worldwide and are commonly resistant to multiple antimicrobial agents. The accessory genetic element, SCCmec, harbors the methicillin resistance determinant and is thought to be horizontally transferred between the principal staphylococcal pathogen, Staphylococcus aureus, and commensal coagulase-negative species, such as S. epidermidis. Recombinations of ubiquitous core genes are also thought to occur within these species, but the frequency, relative size, and biological consequence of recombination in staphylococci is poorly understood. Our long-term goals are to understand how genetic variation contributes to the ecological and evolutionary success of bacterial pathogens. In this application, we investigate the extent to which horizontal genetic transfer has influenced genetic variation in staphylococci. Through sequence-based typing of a prospective collection of clinical isolates of staphylococci, we will test the hypotheses that S. epidermidis recombines it core genes more frequently than S. aureus, and that rare, large intraspecies recombinations result in hybrid S. aureus clones (Aim 1). Through an understanding of genetic background and a molecular characterization of SCCmec, we will test the hypothesis that our local methicillin-resistant S. aureus arise through acquisition of SCCmec from global isolates of the same species, not local congenerics (Aim 2). Moreover, through application of an innovative PCR scanning tool to diverse isolates, we will test the hypothesis that poorly characterized S. aureus of clinical importance harbor novel accessory genes (also Aim 2). Finally, we will examine a potential biological consequence of horizontal genetic transfer in staphylococci. Through a molecular characterization of the ica locus, we will test the hypothesis that genetic background and SCCmec are both independent predictors of biofilm phenotype (Aim 3).