The unique genetic determinant that confers upon E. coli K1 the ability to enter both intestinal epithelial and brain endothelial cells is encoded in a genetic island (GimA) located at the 98 min region of the bacterial chromosome. The four major phylogenetic clusters of meningitic E. coli have been identified by molecular genetic analysis of cerebrospinal fluid isolates from infants with neonatal E. coli meningitis. GimA is predominantly present in the phylogenetic group B2. GimA consists of four operons, ptnIPKC, cglDTEC, gcxKRCI and ibeRAT. The G+C content (46.2%) of the island is substantially different from that (50.8%) of the rest of the E. coli chromosome. As suggested by computer-assisted analysis of the sequences and experimental studies, GimA contributes to carbon source metabolism and substrate transportation. E. coli penetration of human brain microvascular endothelial cells (BMEC) is stimulated by glucose. The stimulating effect of glucose is blocked by exogenous cAMP. It suggests that catabolic regulation may play a role in control of E. coli K1 invasion gene expression and that GimA may contribute to E. coli invasion of the blood-brain barrier through a carbon-source-regulated process. The full understanding of GimA’s functions will provide novel insights into the pathogenesis of E. coli meningitis and suggest new potential targets for preventive interventions against this disease.