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. ? ? ?
| Xie, Yi; Parthasarathy, Geetha; Di Cello, Francescopaolo et al. (2008) Transcriptome of Escherichia coli K1 bound to human brain microvascular endothelial cells. Biochem Biophys Res Commun 365:201-6 |
