The adhesin that has been most closely associated with uropathogenic E. coli is the P fimbria (or pyelonephritis-associated pili [PAP]). The letter designation is derived from the ability of P fimbriae to bind specifically to the P blood group antigen which contains a D-galactose-D-galactose residue. The fimbriae bind not only to red cells but to a specific galactose dissaccharide that is found on the surfaces uroepithelial cells in approximately 99% of the population.

The frequency of the distribution of this host cell receptor plays a role in susceptibility and explains why certain individuals have repeated UTI caused by E. coli. Uncomplicated E. coli UTI virtually never occurs in individuals lacking the receptors.

Uropathogenic strains of E. coli possess other determinants of virulence in addition to P fimbriae. E. coli with P fimbriae also possess the gene for Type 1 fimbriae, and there is evidence that P fimbriae are derived from Type 1 fimbriae by insertion of a new fimbrial tip protein to replace the mannose-binding domain of Type 1 fimbriae. In any case, Type 1 fimbriae could provide a supplementary mechanism of adherence or play a role in aggregating the bacteria to a specific manosyl-glycoprotein that occurs in urine.

Uropathogenic strains of E. coli usually produce siderophores that probably play an essential role in iron acquisition for the bacteria during or after colonization. They also produce hemolysins which are cytotoxic due to formation of transmembranous pores in host cell membranes. One strategy for obtaining iron and other nutrients for bacterial growth may involve the lysis of host cells to release these substances. The activity of hemolysins is not limited to red cells since the alpha-hemolysins of E. coli also lyse lymphocytes, and the beta-hemolysins inhibit phagocytosis and chemotaxis of neutrophils.

Another factor thought to be involved in the pathogenicity of the uropathogenic strains of E. coli is their resistance to the complement-dependent bactericidal effect of serum. The presence of K antigens is associated with upper urinary tract infections, and antibody to the K antigen has been shown to afford some degree of protection in experimental infections. The K antigens of E. coli are "capsular" antigens that may be composed of proteinaceous organelles associated with colonization (e.g., CFA antigens), or made of polysaccharides. Regardless of their chemistry, these capsules may be able to promote bacterial virulence by decreasing the ability of antibodies and/or complement to bind to the bacterial surface, and the ability of phagocytes to recognize and engulf the bacterial cells. The best studied K antigen, K-1, is composed of a polymer of N-acetyl neuraminic acid (sialic acid), which besides being antiphagocytic, has the additional property of being an antigenic disguise.

E. coli strains invade the blood stream of infants from the nasopharynx or GI tract and are carried to the meninges.

The K-1 antigen is considered the major determinant of virulence among strains of E. coli that cause neonatal meningitis. K-1 is a homopolymer of sialic acid. It inhibits phagocytosis, complement, and responses from the host's immunological mechanisms. K-1 may not be the only determinant of virulence, however, as siderophore production and endotoxin are also likely to be involved.

Epidemiologic studies have shown that pregnancy is associated with increased rates of colonization by K-1 strains and that these strains become involved in the subsequent cases of meningitis in the newborn. Probably, the infant GI tract is the portal of entry into the bloodstream. Fortunately, although colonization is fairly common, invasion and the catastrophic sequelae are rare.

Neonatal meningitis requires antibiotic therapy that usually includes ampicillin and a third-generation cephalosporin.

Lysis of a dividing pair of E. coli cells in the presence of a beta-lactam antibiotic. Some beta lactam antibiotics, such as  ampicillin and cephalosporin, are effective in the treatment of meningitis caused by strains of E. coli (above). The beta lactam antibiotics prevent cell wall synthesis and assembly in the bacterium. When the bacterium grows in the presence of the antibiotic, the cell wall becomes progressively weaker and weaker, so the the organism eventually ruptures or "lyses", pouring out its cytoplasmic contents as shown here.