Emergence of E. coli sequence type ST131

描述（由申请人提供）： 一组特定的大肠杆菌，序列型ST 131是一个新认识的，广泛传播的多药耐药（MDR）肠外感染的原因，似乎代表了一个重要的新兴的健康威胁，迫切需要研究。因此，我们建议通过实现以下具体目标来测试以下假设：1。ST 131在过去的十年中已经成为主要的抗-RE。大肠杆菌克隆组在美国，包括退伍军人。 目标1.评估ST 131在美国的年患病率，包括EST-R和EST-SE。大肠杆菌在SENTRY和TRUST收藏（1999-2009）和全国VA医疗中心（2009）。2. ST 131比其它E.大肠杆菌的致病性和寄生性，并存在于食物中。 2.a.在人类中，ST 131比其他E.杆菌 目标2.a.比较ST 131与非ST 131 E退伍军人的临床表现（综合征和严重程度）、疾病结局和宿主受损状态。大肠杆菌临床分离株。 2.b.在小鼠中，ST 131比其他E.大肠杆菌，包括经典的ExPEC菌株。 目标2.b.比较ST 131分离株、非ST 131临床分离株和经典ExPEC菌株的毒力。2.c. ST 131与其他E. coli Aim 2.c.1.在人类中，评估ST 131与非ST 131 EST-RE索引患者家庭成员中肠道共定植的患病率。大肠杆菌临床分离株。 目标2.c.2。在小鼠中，比较ST 131与非ST 131 E。大肠杆菌直接攻击或间接暴露后建立肠道定植。2.d. ST 131存在于零售食品中，与食源性传播一致。 目标2.d.1.确定ST 131在不同零售食品中的流行率。 目标2.d.2.根据基因组背景、毒力基因型和耐药性特征，评估食物来源与人源ST 131分离株的相似性。3.特异性宿主特征预测ST 131感染。 目标3.比较ST 131感染的退伍军人与非ST 131 E的同期对照之间的人口统计学和暴露。大肠杆菌感染。4. ST 131比其它E.杆菌 目标4。比较CTX-M-15（与其他ESBL）编码元件从ST 131（与非ST 131）供体到ST 131（与非ST 131）受体的转移频率。 公共卫生相关性： 与退伍军人健康相关。退伍军人通常患有UTI和各种其他E。大肠杆菌感染（如肺部、腹部和伤口）[16]。大肠杆菌耐药性的出现。大肠杆菌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，可能有毒，难以管理。

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.