Pathogenic E. coli (page 3)
(This chapter has 4 pages)
© Kenneth Todar, PhD
Urinary Tract Infections
Uropathogenic E. coli (UPEC)
cause 90% of the urinary tract
(UTI) in anatomically-normal, unobstructed urinary tracts. The bacteria
colonize from the feces or perineal region and ascend the urinary tract
to the bladder. Bladder infections are 14-times more common in females
than males by virtue of the shortened urethra. The typical patient with
uncomplicated cystitis is a sexually-active female who was first
in the intestine with a uropathogenic E. coli strain. The
are propelled into the bladder from the periurethral region during
intercourse. With the aid of specific adhesins they are able to
The adhesin that has been most closely associated with uropathogenic
coli is the P fimbria (or pyelonephritis-associated
[PAP]). The letter designation is derived from the ability of
P fimbriae to bind specifically to the P blood group antigen which
a D-galactose-D-galactose residue. The fimbriae bind not only to red
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
UTI caused by E. coli. Uncomplicated E. coli UTI
never occurs in individuals lacking the receptors.
Uropathogenic strains of E. coli possess other determinants
virulence in addition to P fimbriae. E. coli with P fimbriae
possess the gene for Type 1 fimbriae, and there is evidence that P
are derived from Type 1 fimbriae by insertion of a new fimbrial tip
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
that occurs in urine.
Uropathogenic strains of E. coli usually produce siderophores
that probably play an essential role in iron acquisition for the
during or after colonization. They also produce hemolysins which are
due to formation of transmembranous pores in host cell membranes. One
obtaining iron and other nutrients for bacterial growth may involve the
lysis of host cells to release these substances. The activity of
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
strains of E. coli is their resistance to the
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
The K antigens of E. coli are "capsular" antigens that may be
of proteinaceous organelles associated with colonization (e.g., CFA
or made of polysaccharides. Regardless of their chemistry, these
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
acid (sialic acid), which besides being antiphagocytic, has the
property of being an antigenic disguise.
Neonatal meningitis affects 1/2,000-4,000 infants. Eighty
of E. coli strains involved synthesize K-1 capsular antigens
is only present 20-40% of the time in intestinal isolates).
E. coli strains invade the blood stream of infants from the
or GI tract and are carried to the meninges.
The K-1 antigen is considered the major determinant of
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
and endotoxin are also likely to be involved.
Epidemiologic studies have shown that pregnancy is associated with
rates of colonization by K-1 strains and that these strains become
in the subsequent cases of meningitis in the newborn. Probably, the
GI tract is the portal of entry into the bloodstream. Fortunately,
colonization is fairly common, invasion and the catastrophic sequelae
Neonatal meningitis requires antibiotic therapy that usually
ampicillin and a third-generation cephalosporin.
Lysis of a dividing pair of E.
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.