Genome-wide screening of E. coli for bacteremia

描述（由申请方提供）：下呼吸道感染是HIV-1感染儿童发病和死亡的主要原因。E.大肠杆菌是导致严重下呼吸道感染并伴有菌血症的常见病原体之一。最近的一份报告也表明，社区获得性菌血症是造成撒哈拉以南非洲和东非至少三分之一婴儿和儿童死亡的原因。大肠杆菌是婴儿菌血症的最常见原因。与社区获得性菌血症相关的相当大的死亡率以及住院和死亡之间的短间隔突出了预防的必要性，例如疫苗。目前尚无有效的预防措施。大肠杆菌等菌血症疫苗。对大肠杆菌的微生物决定因素的认识不完全。大肠杆菌菌血症限制了我们对大肠杆菌新的预防措施的发展。大肠杆菌菌血症。我们进行了一个原型E。coliK 1菌株RS 218基因组，鉴定出22株E.大肠杆菌RS 218特异性基因组岛，大于10 kb，并且在实验室大肠杆菌中不存在。coli K-12菌株MG 1655。使用岛缺失突变体，我们确定了三个新的RS 218特定的岛屿有助于诱导高度的菌血症。我们假设这些RS 218特异性岛屿含有导致菌血症的新微生物决定因素。我们还表明，这些岛屿普遍存在（80-100%），在代表E。大肠杆菌菌株与菌血症患者常见的血清型。本申请旨在确定这些RS 218特异性岛中导致菌血症的新型微生物结构。具体目标如下：1.鉴定和表征RSI 4和RSI 7中影响菌血症的微生物决定因素。2.研究导致菌血症的RSI 21的微生物基础。进一步鉴定和表征有助于E.大肠杆菌菌血症应有助于开发预防措施，如针对大肠杆菌的疫苗。大肠杆菌菌血症。

DESCRIPTION (provided by applicant): Lower respiratory tract infections are a major cause of morbidity and mortality in HIV-1 -infected children. E. coli is one of the common agents responsible for severe lower respiratory tract infections with bacteremia. A recent report has also shown that community-acquired bacteremia is responsible for at least one third of deaths in infants and children in sub-Saharan Africa and E. coli was the most common cause for bacteremia in infants. The considerable mortality associated with community-acquired bacteremia and the short-interval between hospitalization and death highlight the need for prevention such as vaccines. At present, there are no preventive measures available for E. coli bacteremia such as vaccine. Incomplete understanding of microbial determinants contributing to E. coli bacteremia has limited our development for new preventive measures against E. coli bacteremia. We conducted a comprehensive analysis of a prototypic E. coli K1 strain RS 218 genome and identified 22 E. coli RS 218-specific genomic islands that are larger than 10 kb and are absent in laboratory E. coli K-12 strain MG 1655. Using island deletion mutants, we identified that three novel RS 218- specific islands contribute to induction of a high-degree of bacteremia. We hypothesize that these RS 218 - specific islands contain novel microbial determinants contributing to bacteremia. We also showed that these islands are prevalent (80-100%) in representative E. coli strains with serotypes common in patients with bacteremia. This application is to determine the novel microbial structures from these RS 218-specific islands that contribute to bacteremia. Specific aims are as follows: 1. To identify and characterize microbial determinants in RSI 4 and RSI 7 that affect bacteremia. 2. To investigate the microbial basis of RSI 21 that contributes to bacteremia. Further identification and characterization of microbial determinants contributing to E. coli bacteremia should help in development of preventive measures such as vaccines against E. coli bacteremia.