The OmpA outer membrane protein of Escherichia coli and other enterobacteria is a multifaceted protein. This protein is expressed to very high levels and ompA is tightly regulated at the posttranscriptional level. It can function as an adhesin and invasin, participate in biofilm formation, act as both an immune target and evasin, and serves as a receptor for several bacteriophages. Many of these properties are due to four short protein loops that emanate from the protein to the outside of the cell. Herein it is described how the structure of this protein relates to its many functions.

Cystic fibrosis (CF) is a genetic disease characterized by severe neutrophil-dominated airway inflammation. An important cause of inflammation in CF is Pseudomonas aeruginosa infection. We have evaluated the importance of a number of P. aeruginosa components, namely lipopeptides, LPS, and unmethylated CpG DNA, as proinflammatory stimuli in CF by characterizing the expression and functional activity of their cognate receptors, TLR2/6 or TLR2/1, TLR4, and TLR9, respectively, in a human tracheal epithelial line, CFTE29o−, which is homozygous for the ΔF508 CF transmembrane conductance regulator mutation. We also characterized TLR expression and function in a non-CF airway epithelial cell line 16HBE14o−. Using RT-PCR, we demonstrated TLR mRNA expression. TLR cell surface expression was assessed by fluorescence microscopy. Lipopeptides, LPS, and unmethylated CpG DNA induced IL-8 and IL-6 protein production in a time- and dose-dependent manner. The CF and non-CF cell lines were largely similar in their TLR expression and relative TLR responses. ICAM-1 expression was also up-regulated in CFTE29o− cells following stimulation with each agonist. CF bronchoalveolar lavage fluid, which contains LPS, bacterial DNA, and neutrophil elastase (a neutrophil-derived protease that can activate TLR4), up-regulated an NF-κB-linked reporter gene and increased IL-8 protein production in CFTE29o− cells. This effect was abrogated by expression of dominant-negative versions of MyD88 or Mal, key signal transducers for TLRs, thereby implicating them as potential anti-inflammatory agents for CF.

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In most cases, Escherichia coli exists as a harmless commensal organism, but it may on occasion cause intestinal and/or extraintestinal disease. Enterotoxigenic E. coli (ETEC) is the predominant cause of E. coli-mediated diarrhea in the developing world and is responsible for a significant portion of pediatric deaths. In this study, we determined the complete genomic sequence of E. coli H10407, a prototypical strain of enterotoxigenic E. coli, which reproducibly elicits diarrhea in human volunteer studies. We performed genomic and phylogenetic comparisons with other E. coli strains, revealing that the chromosome is closely related to that of the nonpathogenic commensal strain E. coli HS and to those of the laboratory strains E. coli K-12 and C. Furthermore, these analyses demonstrated that there were no chromosomally encoded factors unique to any sequenced ETEC strains. Comparison of the E. coli H10407 plasmids with those from several ETEC strains revealed that the plasmids had a mosaic structure but that several loci were conserved among ETEC strains. This study provides a genetic context for the vast amount of experimental and epidemiological data that have been published.Current dogma suggests the Gram-negative motile bacterium Escherichia coli colonizes the infant gut within hours of birth and establishes itself as the predominant facultative anaerobe of the colon for the remainder of life (3, 59). While the majority of E. coli strains maintain this harmless existence, some strains have adopted a pathogenic lifestyle. Contemporary tenets suggest that pathogenic strains of E. coli have acquired genetic elements that encode virulence factors and enable the organism to cause disease (12). The large repertoire of virulence factors enables E. coli to cause a variety of clinical manifestations, including intestinal infections mediating diarrhea and extraintestinal infections, such as urinary tract infections, septicemia, and meningitis. Based on clinical manifestation of disease, the repertoire of virulence factors, epidemiology, and phylogenetic profiles, the strains causing intestinal infections can be divided into six separate pathotypes, viz., enteroaggregative E. coli (EAEC), enteroinvasive E. coli (EIEC), enteropathogenic E. coli (EPEC), enterohemorrhagic E. coli (EHEC), diffuse adhering E. coli (DAEC), and enterotoxigenic E. coli (ETEC) (33,35,39).ETEC is responsible for the majority of E. coli-mediated cases of human diarrhea worldwide. It is particularly prevalent among children in developing countries, where sanitation and clean supplies of drinking water are inadequate, and in travelers to such regions. It is estimated that there are 200 million incidences of ETEC infection annually, resulting in hundreds of thousands of deaths in children under the age of 5 (55, 64). The essential determinants of ETEC virulence are traditionally considered to be colonization of the host small-intestinal epithelium via plasmid-encoded colonization factors (CFs) and subsequent release of plasmid-encoded heat-stable (ST) ...