The Enterics

 The enterics: are gram-negative bacteria that are part of the normal intestinal flora or cause gastrointestinal disease.  Many of these bacteria are referred to simply by their genus name because there are so many different species in some groups.  The main groups are Enterobacteriaceae, Vibrionaceae, Pseudomonadaceae and Bateroidaceae.  These organisms are also divided into groups based upon biochemical and antigenic properties  These organisms are also divided into groups based upon biochemical and antigenic properties.

Biochemical Classification Biochemical Classification The ability to ferment lactose and convert it into gas and acid. Escherichia coli and most of the enterobacteriaceae ferment lactose while Salmonella, Shigella and Pseudomonas aeruginosa do not. 1) The ability to ferment lactose and convert it into gas and acid. Escherichia coli and most of the enterobacteriaceae ferment lactose while Salmonella, Shigella and Pseudomonas aeruginosa do not. 2) The production of H2S, ability to hydrolyze urea, liquefy gelatin, and decarboxylate specific amino acids.

Some growth media do 2 things at once: 1)They contain chemicals that inhibit the growth of gram-positive bacteria. 2) They have indicators that change colour in the presence of lactose fermentation. A) EMB agar (Eosine Methylene Blue): Methylene blue inhibits gram-positive bacteria, and colonies of lactose fermenters become deep purple to black in this medium. Escherichia coli colonies take on a metallic green sheen in this medium. 2) MacConkey agar: Bile salts in the medium inhibit gram-positive bacteria, and lactose fermenters develop a pink-purple coloration. Biochemical Classification Biochemical Classification

Antigenic Classification  The enterics have 3 major surface antigens: 1) O antigen: This is the most external component of the lipopolysaccharide (LPS) of gram-negative bacteria. The O antigen differs from organism to organism, depending on different sugars and different side-chain substitutions. 2) K antigen: This is a capsule that covers the O antigen. 3) H antigen: This antigenic determinant makes up the subunits of the bacterial flagella, so only bacteria that are motile will possess this antigen. Shigella does not have an H antigen. Salmonella has H antigens that change periodically, protecting it from our antibodies.

The O antigen forms the outer part of the cell membrane, the K antigen wraps around the cell like a capsule, and the arms of the H antigen become wavy flagella The O antigen forms the outer part of the cell membrane, the K antigen wraps around the cell like a capsule, and the arms of the H antigen become wavy flagella Antigenic Classification

Pathogenesis The organisms produce 2 types of disease: 1) Diarrhea with or without systemic invasion. 2) Various other infections including urinary tract infections, pneumonia, bacteremia, and sepsis, especially in debilitated hospitalized patients. Diarrhea 1)No cell invasion:  The bacteria bind to the intestinal epithelial cells but do not enter the cell.  Diarrhea is caused by the release of exotoxins which causes electrolyte and fluid loss from intestinal epithelial cells or epithelial cell death. Watery diarrhea without systemic symptoms (such as fever). Enterotoxigenic Escherichia coli and Vibrio cholera are examples.

2) Invasion of the intestinal epithelial cells:  The bacteria invade the cells. Toxins are then released that destroy the cells.  The cell penetration results in leukocytes in the stool as well as fever. The cell death results in red blood cell leakage into the stool. Examples: Enteroinvasive Escherichia coli, Shigella, and Salmonella enteritidis 3) Invasion of the lymph nodes and bloodstream:  Along with abdominal pain and diarrhea containing white and red cells, this deeper invasion results in systemic symptoms of fever, headache, and white blood cell count elevation.  The deeper invasion can also result in mesenteric lymph node enlargement, bacteremia, and sepsis. Examples: Salmonella typhi, Yersinia enterocolitica, and Campylobacter jejuni. Pathogenesis

Various Other Infections  The enterics are normal intestinal inhabitants and usually live with us in peaceful harmony. In the hospital and nursing homes, however, some bad things happen. They acquire antibiotic resistance and can cause disease in debilitated patients.  They can invade the debilitated patients when Foley catheters are in the urethra or when a patient aspirates vomitus that has been colonized by the enterics.  Because of hospital acquisition, they described as the hospital-acquired gram-negatives or nosocomial gram- negatives. Examples: Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter, Serratia, and Pseudomonas aeruginosa. Pathogenesis

Family Entrobacteriaceae Escherichia coli  Escherichia coli normally resides in the colon without causing disease. Nonpathogenic Escherichia coli (normal flora) + Virulence factors = DISEASE. Virulence factors include the following: 1) Mucosal interaction: a) Mucosal adherence with pili (colonization factor). b) Ability to invade intestinal epithelial cells. 2) Exotoxin production: a) Heat-labile and stable toxin (LT and ST). b) Shiga-like toxin. 3) Endotoxin: Lipid A portion of lipopolysaccharide. 4) Iron-binding siderophore: obtains iron from human transferrin or lactoferrin.

 Diseases caused by Escherichia coli in the presence of virulence factors include the following: 1) Diarrhea. 2) Urinary tract infection. 3) Neonatal meningitis. 4) Gram-negative sepsis, occurring commonly in debilitated hospitalized patients. Diseases

Escherichia coli Diarrhea  Escherichia coli diarrhea may affect infants or adults, death from Escherichia coli diarrhea is usually due to dehydration.  The severity of Escherichia coli diarrhea depends on virulence factors of Escherichia coli. There are 3 groups of diarrhea producing E. coli. 1) Enterotoxigenic Escherichia coli (ETEC):  This Escherichia coli causes traveler's diarrhea. It has pili (colonization factor) that help it bind to intestinal epithelial cells, where it releases exotoxins that are similar to the cholera exotoxins.  The toxins are the heat labile toxin (LT), which is just like the cholera toxin. These exotoxins inhibit the reabsorption of Na and CL and stimulate the secretion of Cl - and HCO3- into the intestinal lumen. Water follows the osmotic pull of these ions, resulting in water and electrolyte loss. This produces a severe watery diarrhea with up to 20 liters being lost a day!!! The stool looks like rice water just like cholera!

2) Enterohemorrhagic Escherichia coli (EHEC):  These Escherichia coli also have a pili colonization factor like the ETEC but differ in that they secrete the powerful Shiga- like toxin ( also called verotoxin) that has the same mechanism of action as the Shigella toxin.  They both inhibit protein synthesis by inhibiting the 60S ribosome, which results in intestinal epithelial cell death.  The diarrhea is bloody (hemorrhagic), accompanied by severe abdominal cramps, and is called hemorrhagic colitis. Hemolytic uremic syndrome (HUS) with anemia, thrombocytopenia (decrease in platelets), and renal failure (thus uremia), is associated with infection by a strain of EHEC, called Escherichia coli 0157:H7.  Numerous outbreaks have occurred secondary to infected hamburger meat served at fast food chains, suggesting that cattle may be a reservoir for EHEC.

3) Enteroinvasive Escherichia coli (EIEC):  This disease is the same as that caused by Shigella.  In fact, the main virulence factor is encoded in a plasmid shared by Shigella and Escherichia coli.  This plasmid gives the bacteria the ability to actually invade the epithelial cells.  EIEC also produces small amounts of Shiga-like toxin. The host tries to get rid of the invading bacteria, and this results in an immune-mediated inflammatory reaction with fever.  White blood cells invade the intestinal wall, and the diarrhea is bloody with white blood cells. Like shigellosis!

Escherichia coli Urinary Tract Infections (UTIs)  The acquisition of a pili virulence factor allows E. coli to travel up the urethra and infect the bladder (cystitis) and sometimes move further up to infect the kidney itself (pyelonephritis).  E. coli is the most common cause of urinary tract infections, which usually occur in women and hospitalized patients with catheters in the urethra.  Symptoms include burning on urination (dysuria), having to pee frequently (frequency), and a feeling of fullness over the bladder.  Culture of greater than 100,000 colonies of bacteria from the urine establishes the diagnosis of a urinary tract infection.

Escherichia coli Meningitis  E. coli is the second most common cause of neonatal meningitis (group B streptococcus is first). During the first month of life, the neonate is especially susceptible. Escherichia coli Sepsis  E. coli is also the most common cause of gram- negative sepsis.  This usually occurs in debilitated hospitalized patients. Septic shock due to the lipid A component of the LPS is usually the cause of death. Escherichia coli Pneumonia  E. coli is a common cause of hospital-acquired pneumonia.