Escherichia coli K1 is a major gram-negative organism causing neonatal meningitis. E. coli K1 binding to and invasion of human brain microvascular endothelial cells (HBMEC) are a prerequisite for E. coli penetration into the central nervous system in vivo. In the present study, we showed using DNA microarray analysis that E. coli K1 associated with HBMEC expressed significantly higher levels of the fim genes compared to nonassociated bacteria. We also showed that E. coli K1 binding to and invasion of HBMEC were significantly decreased with its fimH deletion mutant and type 1 fimbria locked-off mutant, while they were significantly increased with its type 1 fimbria locked-on mutant. E. coli K1 strains associated with HBMEC were predominantly type 1 fimbria phase-on (i.e., fimbriated) bacteria. Taken together, we showed for the first time that type 1 fimbriae play an important role in E. coli K1 binding to and invasion of HBMEC and that type 1 fimbria phase-on E. coli is the major population interacting with HBMEC.The mortality and morbidity associated with neonatal gramnegative bacterial meningitis have remained significant despite advances in antimicrobial chemotherapy. This is mainly attributed to inadequate knowledge of the pathogenesis and pathophysiology of this disease. Escherichia coli K1 is the most common gram-negative bacterium that causes meningitis during the neonatal period (26).E. coli meningitis develops as a result of hematogenous spread, but it is not clear how circulating bacteria cross the blood-brain barrier. Our laboratory has successfully isolated and cultivated human brain microvascular endothelial cells (HBMEC), which constitute the blood-brain barrier (9, 10). We showed that E. coli invasion of HBMEC is a prerequisite for E. coli penetration into the central nervous system in vivo. However, the basis of E. coli-HBMEC interactions involved in binding to HBMEC is incompletely understood.Adherence of bacteria to their host cells is considered the initial step of the pathogenesis of infectious diseases including meningitis. To date OmpA is the only identified determinant that is involved in E. coli K 1 binding to HBMEC (8, 10). Previous reports have implied that S fimbriae might be another potential E. coli K1 factor involved in adherence to HBMEC (3,16,24,32). However, according to our recent data, S fimbriae do not play a significant role in binding of E. coli K1 to HBMEC (35).Type 1 fimbriae are filamentous surface organelles produced by E. coli and mediate mannose-sensitive adhesion of E. coli to various eukaryotic cells. In E. coli K1, type 1 fimbriae have been shown to be important for oropharyngeal colonization in a neonatal rat model (4). Type 1 fimbriae are encoded by a fim gene cluster, including at least nine genes required for their biosynthesis (20). The fimbriae are composed primarily of the major FimA protein and a small tip structure containing FimF, FimG, and FimH (12). The lectin-like adhesin, FimH, located at the tip of the fimbrial shaft is responsible for the mannosesens...

Tularemia is a zoonotic infectious disease caused by the facultative intracellular bacterium Francisella tularensis. The initial clinical presentation and dominant features of this condition reflect the mode of transmission and the route of infection. The ulceroglandular form, most frequently acquired from bites of arthropods, is characterized by an initial papular skin lesion that can progress to an eschar or ulcer with regional lymphadenopathy. Inhalation of aerosolized bacteria or secondary hematogenous dissemination of infection to the lungs results in pneumonic tularemia characterized by fever, a broad range in the severity of respiratory symptoms, and a high mortality rate. In the so-called "typhoidal" form of tularemia, patients present with similar systemic symptoms without a clear focus of primary infection. They may show sepsis and rhabdomyolysis with multiorgan system failure, including renal impairment. Following pulmonary and gastrointestinal infection, systemic dissemination of the pathogen leads to the colonization of the liver, where organisms infect both macrophages and hepatocytes (4, 6). At autopsy, the livers of infected human beings often show areas of focal coagulation necrosis throughout the parenchyma of the organ (18).The infection of mice with the live vaccine strain (LVS) of F. tularensis subsp. holarctica is a commonly used animal model and is associated with the formation of multifocal hepatic microgranluomas containing CD11b ϩ macrophages and Gr-1 ϩ