Sunday, August 6, 2017

When good bacteria go bad: Shiga toxin-producing Escherichia coli

Two young children, siblings - brother and little sister, got sick last month. The little girl sadly succumbed and passed away. Her older brother was gravely ill, fighting for his life, slowly recovered, and is now thankfully home. What could have caused this unfathomable tragedy? A strain of normally beneficial bacteria, Escherichia coli, or E. coli (E-coal-I).

E. coli is a kind of bacteria that lives in the guts of mammals, including humans, cows, sheep, and goats. Garden variety E. coli doesn't cause any harm, maybe a little gas. Sometimes it ends up in your urethra and causes a urinary tract infection. No big deal (unless it's resistant to antibiotics, but we've gone there already). Unfortunately, there also exist pathogenic E. coli. These are the strains of E. coli that can make us sick. You can think of different strains of a certain bacteria as flavors of ice cream. Vanilla, chocolate, mint chocolate chip, Rocky Road, whatever you like. It's all ice cream (E. coli), but it comes in many different flavors (strains). There are strains of E. coli that are sticky and adhere to the lining of your intestines more than others. Some of those sticky strains also can cause you to have diarrhea, and a lot of it. As your intestines become a mad torrent of watery contents, many of your normal beneficial bacteria are swept away in the tide. The E. coli strains that are more sticky are able to hang on tight. Then once the rest of your bacteria are gone, they can take over the area without any competition. There are several different groupings of pathogenic E. coli and to talk about them there's going to be a lot of long words that are hard to pronounce and lots of abbreviations. Hang on tight. First thing to note: the prefix "entero" refers to the intestine. 

Enterotoxigenic E. coli, or ETEC,
Enteropathogenic E. coli, or EPEC,
Enteroaggregative E. coli, or EAEC,
Enteroinvasive E. coli, or EIEC,
Diffusely adherent E. coli, or DAEC,
and Shiga toxin-producing E. coli, or STEC. Also known as Enterohemorrhagic (EHEC), or Verocytotoxin-producing (VTEC). 

The groups listed above all have varying abilities to stick to your intestinal wall, to resist your stomach acids, and to cause you to have diarrhea that can be bloody. STEC (S-teck) is what you hear about in the news, mostly when there is an outbreak of illness caused by contaminated food. STEC is a bad guy, a really bad, bad bacteria. STEC is what we're talking about here. 

The kind of STEC that you've probably heard of is called E. coli O157:H7, sometimes referred to as E. coli O157 or simply as O157. The "O" number refers to an antigen on the surface of the bacterial cell wall. The "H" number is an antigen on the flagella (whip-like appendages that allow the bacteria to swim around). I don't want to get too into the weeds about bacterial cell wall structures and whatnot. What's important is there is tremendous variability of "O" and "H" antigens among bacteria like E. coli and so we use them in microbiology to separate, categorize, and name. This is called serotyping. E. coli O157:H7 is a serotype of STEC. There are many other serotypes of STEC besides O157. We have O111, O26, O104, O121, and O145 to name a handful; there are a lot more. Last year there was a multi-state outbreak of STEC infections caused by O121 and O26 that was associated with consuming raw flour, like eating undercooked baked goods or pizza dough, or licking the spoon when you make cookies. In 2011, there was a massive outbreak of STEC infections caused by O104:H4 associated with eating contaminated raw fenugreek sprouts: 4,075 cases and 50 deaths in 16 countries.

Why does STEC cause so many illnesses? Why do people get so sick? STEC produces toxins called Shiga toxins, named after Dr. Kiyoshi Shiga - the doctor who discovered the bacteria responsible for dysentery. Those of you old enough, and young enough, and Minnesotan enough, to have played the game Oregon Trail may recall members of your caravan dying of dysentery on the long journey west. 
(Image: MECC)

Dysentery is a diarrheal illness caused by bacteria called Shigella which are very similar to E. coli, and produce the same kind of toxin. 80 years after the discovery of the Shiga toxin that causes dysentery, researchers discovered the toxins in certain strains of E. coli, the STECs. Shiga toxins are toxic to the kinds of cells that line the intestines, causing damage to the lining. In the grand scheme of things, having a damaged intestinal wall doesn't seem all that terrible. You'll probably have a "stomach ache" and some diarrhea, albeit bloody which is not awesome. But you'll probably get better in a few days and be back to somewhat normal. But remember I said the STECs are the really bad guys. Sometimes an infection with STEC can lead to a complication called hemolytic uremic syndrome, or HUS. 

HUS is a disease that involves the kidneys, red blood cells, and platelets (cells that clot your blood). It most often affects young children and can cause severe illness and death. The two siblings I told you about at the beginning both developed HUS. This disease can also be caused by other bacterial infections, some viruses, medications, and other reasons. HUS occurs in about 5-10% of STEC infections. 

Somehow (researchers are still working this out), the toxins get out of the intestines where they are drawn to cells that produce what are called Gb3 receptors. A receptor is defined as "a region of tissue, or a molecule in a cell membrane, that responds specifically to a particular neurotransmitter, hormone, antigen, or other substance." Which I suppose is a fancy way of saying it's like an iPhone charger port. Your charger cord (Shiga toxin) only works for an iPhone port, and only a specific version of the iPhone port. Shiga toxins are able to bind (plug in) to Gb3 receptors. Kidneys have more Gb3 receptors than any other part of your body and kids' kidneys have more Gb3 receptors than adults. This is likely why kids are more likely to develop HUS due to an STEC infection than are adults. And also why HUS leads to kidney failure in up to 70% of patients. Some patients also have neurological symptoms like altered consciousness and seizures. The processes by which HUS causes kidney failure and other organ damage are complicated and I've already gone on for quite a long time spewing technical medical jargon so I'll spare you. Wikipedia has a pretty good page on HUS, as does Medscape, if you're so inclined. 

Treatment for HUS is largely supportive and may include dialysis while the kidneys recover. Treatment of the STEC infection with antibiotics is not generally recommended; there is some evidence to suggest that the bacteria release more toxins, leading to increased risk of HUS. Other evidence shows certain antibiotics may prevent HUS. More studies are needed. What we do know is that antibiotic treatment has little effect on the duration or severity of the gastrointestinal infection symptoms.

So what can you do? 
I talked about how STEC infections end up in the news when there is an outbreak of illness associated with contaminated food. I think most people of a certain age associate O157 with undercooked hamburger because of a large outbreak associated with eating hamburgers from a popular fast food restaurant called Jack In The Box. We know that undercooked meat can make us sick and we take steps to ensure that doesn't happen. What many people don't realize, however, is that cooking meat properly does nothing to stop contamination of the side salad from using the same cutting board or utensils for handling both raw meat and vegetables. 

People may also not be aware the same bacteria that can be found in hamburger meat can also be found in other foods like raw flour, lettuce and other leafy greens, sprouts, raw (unpasteurized) milk, and pretty much anything else that has come into contact with poop contaminated with STEC. STECs are found in the guts of ruminants like goats, sheep, deer, and cattle. These animals don't have any of the Gb3 receptors we talked about earlier, so they don't show symptoms. The bacteria are just living in the gut and hitch a ride out of the body on occasion in the animal's poop. You may have noticed cattle, goats, and others don't concern themselves with hygiene the way we humans do. They just poop and walk away. Sometimes the poop is a little loose and runs down a leg or splatters on an utter; sometimes they walk in it and spread it around on their hooves. Animals in fields, barns, large-scale feed lots, and petting zoos may take a snooze on a hot day and lay down in their own feces and the poo of their pals. The bacteria in the poop get transferred to the animal's hide. Then we head to the petting zoo and give that cute little animal a hug or a pet or a scratch. And if we're a little kid, we pretty much instantly put our hand in our mouth. Animals carrying STEC may graze near a field of lettuce, or that field of lettuce may be fertilized with cattle feces that hasn't been properly composted to reduce the numbers of bacteria. Insects, birds, and rodents can pick up STEC on their feet and transfer those bacteria to a field of wheat. 

I don't want to make it seem like there isn't anything you can do. There is! Following safe food handling guidelines and hand hygiene are the best ways to protect yourself and your family.
  • Never eat raw or undercooked ground beef and cook all meat thoroughly according to guidelines
  • Dedicate one cutting board and utensils for handling meat and another for vegetables
  • Wash cutting boards, utensils, and counters after handling raw meat
  • Don't eat raw or undercooked dough
  • Wash your hands before cooking, after handling raw meat, and before you eat
  • Wash your hands and your children's hands when at a petting zoo or fair or carnival or any other place where you have encountered and touched animals and their surroundings
  • Wash your hands after handling dirty diapers and helping kids use the bathroom
  • Avoid swallowing water in lakes, streams, ponds, swimming pools, and splash pads
I hope I didn't freak you out too much. Be safe and have a happy summer!