Horizontal Genetic Transfer In Staphylococci

描述（由申请人提供）：耐甲氧西林葡萄球菌是世界范围内医院感染的主要原因，通常对多种抗菌药物具有耐药性。辅助遗传因子SCCmec具有甲氧西林耐药性决定因素，被认为在主要葡萄球菌病原体金黄色葡萄球菌和共生凝血酶阴性物种（如表皮葡萄球菌）之间水平转移。普遍存在的核心基因重组也被认为发生在这些物种中，但葡萄球菌中重组的频率、相对大小和生物学后果尚不清楚。我们的长期目标是了解遗传变异如何促进细菌病原体的生态和进化成功。在这个应用中，我们研究水平遗传转移对葡萄球菌遗传变异的影响程度。通过对临床分离葡萄球菌的前瞻性收集进行基于序列的分型，我们将验证表皮葡萄球菌比金黄色葡萄球菌更频繁地重组其核心基因的假设，以及罕见的、大规模的种内重组导致金黄色葡萄球菌杂交克隆的假设（目的1）。通过对SCCmec的遗传背景和分子特征的了解，我们将验证本地耐甲氧西林金黄色葡萄球菌是通过从同一物种的全球分离株获得SCCmec而不是本地同源菌株而产生的假设（目标2）。此外，通过一种创新的PCR扫描工具对不同分离株的应用，我们将验证一种假设，即对临床重要的金黄色葡萄球菌特征不明确，含有新的辅助基因（同样是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。通过对ica位点的分子表征，我们将检验遗传背景和SCCmec都是生物膜表型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).