Emergence of E. coli sequence type ST131

ST131 型大肠杆菌序列的出现

• 批准号: 8195979
• 负责人: JAMES R JOHNSON
• 金额: --
• 依托单位: MINNEAPOLIS VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2013-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8195979
• 关键词: Abdomen; Accounting; Affect; Affinity; Antimicrobial Resistance; Cefotaxime; Cephalosporin Resistance; Cephalosporins; Characteristics; Clinical; Collection; Country; Cyclophosphamide; Data; Domestic Fowls; Elements; Escherichia coli; Escherichia coli Infections; Exhibits; Food; Food Supply; Frequencies; Future; Genomics; Genotype; Health; Hospitals; Household; Human; Infection; Intervention; Intestines; Laboratories; Lung; Medical center; Meningitis; Multi-Drug Resistance; Mus; Outcome; Outpatients; Patients; Persons; Prevalence; Reporting; Resistance; Resistance profile; Risk; Sepsis; Severity of illness; Source; Syndrome; Testing; Urinary tract infection; Veterans; Virulence; Virulent; antimicrobial; base; beef; beta-Lactamase; demographics; fluoroquinolone resistance; foodborne; genetic element; indexing; member; mouse model; public health relevance; transmission process

DESCRIPTION (provided by applicant): A specific group of Escherichia coli, sequence type ST131 is a newly recognized, widely disseminated cause of multi-drug-resistant (MDR extraintestinal infections that appears to represent an important emerging health threat in urgent need of study. Therefore, we propose to test the following Hypotheses by accomplishing the following Specific Aims: 1. ST131 has emerged in the past ten years as the predominant FQ-R E. coli clonal group in the US, including among veterans. Aim 1. Assess the annual prevalence of ST131 in the US among FQ-R and FQ-S E. coli in the SENTRY and TRUST collections (1999-2009) and from VA medical centers nationwide (2009). 2. ST131 is more fit than other E. coli in the pathogenic and commensal niches, and is present in foods. 2.a. In humans, ST131 causes more severe infections, in less compromised hosts, than other E. coli. Aim 2.a. Compare clinical presentation (syndrome and severity), illness outcome, and host compromise status among veterans with ST131 vs. non-ST131 E. coli clinical isolates. 2.b. In mice, ST131 is more virulent (UTI, sepsis) than other E. coli, including classic ExPEC strains. Aim 2.b. Compare the virulence of ST131 isolates, non-ST131 clinical isolates, and classic ExPEC strains. 2.c. ST131 exhibits enhanced intestinal colonization and host-to-host transmission, vs. other E. coli Aim 2.c.1. In humans, assess the prevalence of intestinal co-colonization among household members of index patients with ST131 vs. non-ST131 FQ-R E. coli clinical isolates. Aim 2.c.2. In mice, compare ST131 with non-ST131 E. coli for establishment of intestinal colonization after direct challenge or indirect exposure. 2.d. ST131 is present in retail foods, consistent with foodborne transmission. Aim 2.d.1. Determine the prevalence of ST131 in diverse retail foods. Aim 2.d.2. Assess the similarity of food-source versus human-source ST131 isolates according to genomic background, virulence genotype, and resistance profile. 3. Specific host characteristics predict ST131 infection. Aim 3. Compare demographics and exposures among veterans with ST131 infection versus concurrent controls with non-ST131 E. coli infection. 4. ST131 is more receptive to CTX-M-15-encoding genetic elements than are other E. coli. Aim 4. Compare transfer frequencies for CTX-M-15 (vs. other ESBL)-encoding elements from ST131 (vs. non-ST131) donors to ST131 (vs. non-ST131) recipients. PUBLIC HEALTH RELEVANCE: Relevance to Veterans Health. Veterans commonly suffer from UTI and diverse other E. coli infections (e.g. of lung, abdomen, and wounds) [16]. Emerging antimicrobial resistance in E. coli increases the risk that veterans will receive inappropriate initial antimicrobial therapy, and makes appropriate therapy more expensive, potentially toxic, and difficult to administer.

描述(由申请人提供)： 肠外多药耐药(MDR)肠外感染是一种新发现的广泛传播的多重耐药(MDR)肠外感染，是一种新发现的、急需研究的新出现的健康威胁。因此，我们建议通过实现以下特定目标来检验以下假设：1.在过去的十年中，ST131已经成为美国主要的FQ-R大肠杆菌克隆群，包括在退伍军人中。目的1.评估1999年至2009年哨兵和托管所收集的FQ-R和FQ-S大肠埃希菌以及2009年全国退伍军人管理局医疗中心FQ-R和FQ-S的ST131感染率。2.ST131在致病生态位和共生生态位上比其他大肠杆菌更适合，并存在于食品中。2.a.在人类中，与其他大肠杆菌相比，ST131在受感染较少的宿主中会引起更严重的感染。目标2.a.比较患有ST131和非ST131临床分离株的退伍军人的临床表现(症状和严重程度)、疾病结局和宿主妥协状态。2.B.在小鼠中，ST131比其他大肠杆菌(包括经典的ExPEC菌株)毒力更强(尿路感染、败血症)。目标2.b.比较ST131分离株、非ST131临床分离株和ExPEC经典株的毒力。2.C.与其他大肠杆菌Aim 2.c.1相比，ST131表现出更强的肠道定植和宿主到宿主的传播。在人类中，评估具有ST131与非ST131 FQ-R大肠杆菌临床分离株的索引患者家庭成员之间肠道共定植的流行率。目标2.c.2。在小鼠中，比较ST131和非ST131大肠杆菌在直接攻击或间接暴露后建立肠道定植的情况。2.D.ST131存在于零售食品中，与食源性传播一致。目标2.d.1。确定不同零售食品中ST131的流行率。目标2.d2。根据基因组背景、毒力基因和耐药性图谱，评估食物来源和人源ST131分离株的相似性。3.特定宿主特性可预测ST131的感染。目的3.比较患有ST131感染的退伍军人和同期对照的非ST131感染的退伍军人的人口统计学和暴露情况。4.ST131对CTX-M-15编码的基因元件的接受性强于其他大肠杆菌。目的4.比较CTX-M-15(与其他ESBL编码元件相比)从ST131(与非ST131)供体到ST131(与非ST131)受体的转移频率。 公共卫生相关性： 与退伍军人健康的相关性。退伍军人通常患有尿路感染和各种其他大肠杆菌感染(例如肺、腹部和伤口)[16]。在大肠杆菌中出现的抗菌素耐药性增加了退伍军人接受不适当的初始抗菌治疗的风险，并使适当的治疗更加昂贵、潜在的毒性和难以管理。