Horizontal Genetic Transfer In Staphylococci

葡萄球菌的水平遗传转移

• 批准号: 7917022
• 负责人: David Ashley Robinson
• 金额: $ 11.69万
• 依托单位: UNIVERSITY OF MISSISSIPPI MED CTR
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7917022
• 关键词: Affect; Base Sequence; Biological; Biological Assay; CCDC6 gene; Clinical; Coagulase; Collection; Complex; Data; Frequencies; Genes; Genetic; Genetic Recombination; Genetic Structures; Genetic Variation; Genomics; Genus staphylococcus; Goals; Hospitals; Hybrids; Indium; Membrane Proteins; Methicillin; Methicillin Resistance; Microbial Biofilms; Molecular; Nosocomial Infections; Phenotype; Phylogenetic Analysis; Population; Population Genetics; Relative (related person); Resistance; Scanning; Series; Single Nucleotide Polymorphism; Staphylococcus aureus; Testing; Variant; Virulence; Whole Genome PCR; antimicrobial drug; genetic element; genome sequencing; improved; innovation; methicillin resistant Staphylococcus aureus; novel; pathogen; prospective; success; tool; trait

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).

描述（由申请人提供）：耐甲氧西林葡萄球菌是全世界医院感染的主要原因，并且通常对多种抗菌药物具有耐药性。辅助遗传元件 SCCmec 含有甲氧西林抗性决定子，被认为在主要葡萄球菌病原体金黄色葡萄球菌和共生凝固酶阴性物种（例如表皮葡萄球菌）之间水平转移。普遍存在的核心基因的重组也被认为发生在这些物种中，但人们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促进细菌病原体的生态和进化成功。在此应用中，我们研究了水平遗传转移对葡萄球菌遗传变异的影响程度。通过对预期的葡萄球菌临床分离株进行基于序列的分型，我们将测试以下假设：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，并且罕见的大规模种内重组会产生杂种金黄色葡萄球菌克隆（目标 1）。通过了解 SCCmec 的遗传背景和分子特征，我们将检验以下假设：我们当地的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而不是当地同种中获得 SCCmec 产生的（目标 2）。此外，通过对不同分离株应用创新的 PCR 扫描工具，我们将检验以下假设：具有临床重要性的特征较差的金黄色葡萄球菌含有新的辅助基因（也是目标 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 ica 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（目标 3）。