Escherichia Coli – Enteric Bacteria

00:01 Let's now look at E. coli in terms of its causing enteric disease.

00:05 E. coli, Escherichia coli, very famous bacteria, is a member of the human gut microbiota.

00:12 Most of the strains are avirulent.

00:14 All the strains that we have in us as long as they stay in the gut, they're okay.

00:19 Now occasionally, E. coli escapes the gut and causes other infections.

00:25 You know, the way we are built is not ideal.

00:27 We have our anus right next to our genitals so bacteria come out in feces, it's easy to contaminate the genitals and this is what happens in many people.

00:37 They get urinary tract infections where E. coli escapes from the intestine and infects the urinary tract, can go all the way up to the kidneys, and even spread beyond that.

00:49 So, these E. coli are just normal flora which aren't in the right place in the urinary tract and elsewhere and they can cause serious infections.

00:57 We're not gonna talk about these today but I want you to know that the E. coli within you can sometimes cause problems within you and those can spread to other people as well.

01:07 What I'm talking about today are E. coli that come from other sources, either humans or animals that are special strains that now have the ability to cause enteric infections. Alright? Other E. coli strains -- that's a picture of E. coli by the way. They're rods, beautiful rods.

01:24 Other E.coli strains not from you, from other people or other animals can be pathogenic.

01:30 So, these are spread by fecal-oral contamination and this can happen during food preparation if a food preparer has this E. coli in them.

01:39 Perhaps they have asymptomatic enteric infection with the strain that they acquired from somewhere else.

01:44 They can contaminate the food and you will get it.

01:46 Manure contamination is a big one.

01:49 Cows have lots of E. coli strains in them which don't hurt the cows at all but if they get into people, they cause diarrhea.

01:58 And often, cow manure contaminates food of various sources.

02:03 So, for example, crops are often irrigated with gray water that isn't so clean.

02:07 It has cow manure in it and it contaminates the crops and they're not washed properly, you eat them, and you get infection.

02:15 So, washing crops with contaminated water or just consumption of contaminated water that somehow contains manure from cows or even human feces again, from people who are infected with these unusual strains of E. coli.

02:28 So the first strain we'll talk about--and there are several--is called Enterotoxigenic E. coli or ETEC.

02:35 There are lots of abbreviations we're gonna be hitting here.

02:38 We'll show you a table at the end so you can remember them all.

02:41 ETEC causes Travelers diarrhea. Why does it cause that? You go to another country, within a day or two you get diarrhea.

02:48 Watery diarrhea after you've eaten some local food. That's Travelers diarrhea.

02:54 It's annoying but it happens. It affects children and adults all over the world.

02:58 You've probably heard of it. It's caused by ETEC strains of E. coli.

03:03 These use fimbriae or pili adhesins to bind to enterocytes in the small intestine.

03:10 Very much like the fimbria that we've talked about.

03:13 And these strains, the ETEC strains, make two enterotoxins.

03:18 An enterotoxin is simply a toxin produced by the bacteria that affects your enteric tract.

03:25 The ETEC strains of E. coli produce an LT enterotoxin.

03:30 This is very much like a cholera toxin.

03:32 It gets into the cell, causes increased amounts of cyclic AMP.

03:37 And what does it do to sodium levels? Pumps it into the cell, pumps out chloride, there you go.

03:44 You get your watery diarrhea as the cell then pumps out water to try and compensate.

03:48 LT enterotoxin. The other toxin is called ST.

03:51 This causes cyclic GMP accumulation in cells which also results in secretion of fluid and electrolytes contributing to the watery diarrhea.

04:01 So two enterotoxins, both of their effect is to cause imbalance in the ion makeup of the cell and the cell excretes water and you get watery diarrhea.

04:12 ETEC E. coli, two enterotoxins.

04:16 These bacteria are not invasive. They sit on the surface of your epithelial cells in your gut.

04:23 They attach to the gut surface by the pilli and they sit there and make toxins and you have diarrhea.

04:29 They don't go in, they're not invasive.

04:31 So important distinction, these are simply bacteria very much like the cholera, vibrio cholerae, sits on the surface, they do not invade.

04:40 Let's look at another type of E. coli. These are Enteropathogenic E. coli or EPEC.

04:46 Hard to remember ETEC, EPEC now.

04:49 Enteropathogenic, these also cause watery diarrhea but these bacteria are slightly different.

04:56 They do not have fimbriae to attach. They have other things.

05:01 They have no ST and they have no LT toxins.

05:05 Remember, those are two toxins produced by the ETEC strains which are important for causing the watery diarrhea but the EPEC strains of E. coli do not produce those toxins.

05:16 So how do they produce diarrhea? These EPEC strains of E. coli adhere to the intestinal cells via two proteins.

05:27 One is shown as a helical protein in the first panel of the illustration and the second is via an intimin adhesion which is the small blue box and these cause the bacteria to adhere very tightly to the epithelial surface and we think that binding changes the surface and that causes the diarrhea.

05:47 We call this adhesion inephasement and it's the deformation of the villi caused by bacterial attachment and that causes the diarrhea.

05:56 Not the elaboration of toxins as with the ETEC strains, alright? So those are Enteropathogenic E. coli.

06:04 The next strain that we'd like to talk about are called Enteroaggregative E. coli or EAggEC.

06:13 These are strains only found in people and I mentioned this because these are frequently seen in AIDS patients.

06:21 So, these kinds of diarrheal diseases are associated with immunosuppression.

06:26 Enteroaggregative E. coli have fimbriae as you can see in this picture which aggregate cells in culture and that's why they are called enteroaggregative strains.

06:40 They bind to the intestinal mucosa, they cause watery diarrhea without fever, they are non-invasive as are the other strains.

06:48 They do produce a number of toxins.

06:50 One of them is alpha-hemolysis and they produce an ST enterotoxin similar to that of the ETEC strains.

06:59 The ST enterotoxins cause an increase in cellular cyclic GMP and this results in ion imbalances leading to watery diarrhea.

07:11 Okay, so those bacteria, the vibrio and the various strains of E. coli cause watery, non-invasive diarrhea.

07:21 Let's now turn to enteric bacteria that are invasive.

07:26 They go beyond the surface of the epithelial cells, they invade the sub-mucosa and they become systemic, and they also cause bloody diarrhea which is also known as dysentery.

07:38 So, when you have blood in your diarrhea, it's no longer watery diarrhea. It is dysentery.

07:43 The intestinal pathogens, they do this structurally damage the large intestine and they invade the mucosa and that damage and invasion leads to bloody diarrhea or dysentery.

08:00 So bloody diarrhea or dysentery, 30 passages a day.

08:05 Not as much as cholera but 30 a day is still a lot.

08:09 So, it is stools with blood, mucus, and puss in them. That's the definition of the dysentery.

08:17 These are life-threatening infections. They require treatment with antibiotics.

08:22 It's not sufficient to provide water rehydration because here the bacteria are in your bloodstream and you can have all the water in the world, you're not gonna get rid of those bacteria unless you take antibiotics.

08:36 They need serious treatment.

08:38 And we're gonna talk about two different genre of bacteria that cause bloody diarrhea and dysentery.

08:44 First, we're back to E. coli but these are again, different strains of E. coli that cause invasive diarrhea.

08:51 So, you see, E. coli can be very different depending on what genes it has.

08:55 The first is the enterohemorrhagic or EHEC strains of E. coli and the second, the enteroinvasive strains or EIEC strains of E. coli, and the Shigella.

09:09 Let's move to E. coli. One kind of E. coli, enterohemorrhagic E. coli or EHEC.

09:16 These are strains of E. coli that are frequently in the news so you may have heard of them.

09:21 EHEC E. coli they cause nonfebrile, no fever, bloody diarrhea, and hemorrhagic colitis is the name of this syndrome when caused by EHEC strains.

09:33 So how does this work? These are strains of E. coli that produce toxin.

09:39 They produce a Shiga toxin which we've heard about before.

09:43 It can cause ion imbalances leading to water secretion and there are several names for these strains as a consequence besides EHEC.

09:50 They're also called STEC which means Shiga toxin-producing E. coli or HUSEC, hemolytic uremic syndrome-associated enterohemorrhagic E. coli.

10:02 As well see, that's one of the syndromes associated with infection or verocytotoxin-producing E. coli, VTEC strains.

10:10 All these are the same name for EHEC-type strains.

10:13 They are often classified according to the O-antigen.

10:18 Here we're showing lipopolysaccharide which is a component of the outer membrane of these gram negatives.

10:23 You may remember this. If not, you can go back to one of the earlier lectures in which we talked about this in detail.

10:29 One of the components of LPS is the O-antigen which you can see at the top there and the O-antigen is how we categorize many of these strains.

10:38 And so for example, you probably have heard of E. coli O157:H7.

10:46 This is a strain that's caused many outbreaks of dysentery and it's often acquired from cows.

10:54 If you eat undercooked hamburger, you can be infected with an O157 strain.

11:00 The cows have this bacterium in their intestines. It does not harm them whatsoever but if it gets to you somehow via the meat, the meat can easily been contaminated with cow feces during the preparation.

11:13 If you don't cook it enough, you don't kill the organism, you'll get infected, you will get the diarrheal disease from it. You can also get it from contaminated water.

11:22 Again, if the water is contaminated with manure in some way by improper preparation, you will get this disease. O157 is a specific kind of O-antigen so now you know what this means.

11:35 The lipopolysaccharide, those O-antigens at the very top in the previous slide, that's what it's categorizing this as O157. And if you're interested, the H7 is a flagellar antigen.

11:48 The flagellum is the molecule that propels these bacteria around to move.

11:53 This is one of the proteins of the flagellum, the H protein.

11:56 So now you know that these EHEC strains are categorized by lipopolysaccharide and flagellar antigens.

12:04 These bacterium may cause something called Hemolytic-uremic syndrome and this is accompanied by hemolytic anemia.

12:13 The red blood cells are lysing so you become anemic.

12:17 You have not enough red blood cells. Thrombocytopenia and kidney failure.

12:21 These are all associated with these EHEC infections.

12:25 A very large outbreak of an EHEC strain occurred a number of years ago in Germany and these were caused by a slightly different strain.

12:35 A brand new one that hadn't been seen before: O104:H4.

12:39 Now you know exactly what the O and the H-antigens are.

12:44 This caused a big outbreak in Germany of food-born disease and it was traced to contaminated vegetables.

12:51 It was actually an EaggregateEC strain.

12:54 Now, we talked about the EAggEC strain is causing diarrhea in AIDS patients.

12:58 Somehow, this EAggEC strain acquired a gene for the Shiga toxin which causes the watery diarrhea producing this new strain O104:H4.

13:10 It was present on vegetables probably via contamination with dirty water and it wasn't washed properly and if you eat uncooked vegetables and you know, people do like to eat their carrots uncooked and even cucumbers and sprouts.

13:24 Particularly sprouts are never cooked and so these are common ways to get this infection.

13:30 But this is an interesting case where the Shiga toxin had been newly acquired by one of these other strains.

13:37 In the bowel, these EHEC strains produce proteins that allow them to attach and efface like the EPEC strains so not all of them produce toxins.

13:48 This particular strain in the German outbreak had acquired a Shiga-like toxin but most of the EHEC strains simply attach and efface the face of the surface of the villi and that causes the diarrhea.

14:00 The production of a Shiga toxin if it's present may be responsible for a cytokine response in the mucosa.

14:07 You can get profuse bleeding and this is caused by interaction of the cytokines that we produce with the Shiga toxins which damages the blood vessel and a major complication as I mentioned is this hemolytic-euremic syndrome.

14:20 This is a combination of damage to small blood vessels. If this happens in the kidney, you have kidney problems and if you have extensive lysis of red blood cells, the remaining pieces of the red blood cells get hung up in the kidney, further complicating kidney function.

14:37 These strains can also invade the brain where it can cause thrombocytopenic purpura and the Shiga toxins are on phages.

14:47 And again, the Shiga toxin originally seen in Shigella causing the loss of water from the intestine.

14:54 These are on phages so they're mobile.

14:56 These toxins can spread from bacteria to bacteria and that's presumably why the E104 German strain arose by infection with the phage that delivered the Shiga toxin gene at some point.

15:07 These toxins are taken into cells and inhibit protein synthesis.