Vibrio Cholerae – Enteric Bacteria

00:01 Let's talk about vibrio first. Vibrio cholerae, a cause of watery diarrhea, this bacterium is never a member of the human microbiome. It is not part of our normal flora. It is a normal inhabitant of the environment, in particular, coastal estuarine waters. They live in close association with phytoplankton in the waters and so they're living there and they're very happy to be living there, so why do they infect us? Well, sometimes we enter this ecosystem, or the organisms contaminate our drinking water or food. Somehow they can get into our food or drinking water, typically when sewage systems aren't working properly, vibrio can get into our water supply and then they infect us and cause problems.

00:55 Cholera is the disease caused by vibrio cholerae. It is the paradigm for secretory diarrhea. It is upon which everything is based our knowledge understanding this condition. Vibrio cholerae encodes two toxins that are important for causing watery diarrhea. Once you ingest the bacteria, they get into your small intestine, they make cholera toxin, which is shown on the right of the slide there, CTX, and it's composed of an A subunit, which is the effector part and the five B subunits, we talked about this in a previous lecture, and a toxin-coregulated pilus, that means the other toxin, the toxin-coregulated piluses made at the same time as the cholera toxin and this pilus allows the cholera to adhere to the surface of the mucosal epithelium, which is shown in the diagram on the right. So you have vibrios, which are curved bacteria with a flagellum, they enter the intestinal tract, they make this pilus to adhere and they produce cholera toxin at the same time. What does cholera toxin do? It binds to a receptor on the surface via the B subunits to internalize and the A subunit is released into the cytoplasm of the cell, this A subunit causes an increase in intracellular cyclic AMP, it raises the levels. This causes the imbalance in sodium absorption; so it inhibits sodium absorption, increases chloride secretion, as a consequence, the cells try and adjust, they get rid of water, bingo, watery diarrhea. So cholera toxin is what does this by messing up the sodium chloride balance, there you get your watery diarrhea. Very simple straightforward fact. Now this watery diarrhea is a consequence of the toxin, what it does, of course, it washes the cholera bacteria out of your intestine and that helps to spread the infection. If you happen to be in a place where the sewage treatment isn't very good, you will excrete cholera bacteria into the sewage and it will then infect someone else via contaminated food or water.

03:19 The challenge with cholera is to prevent dehydration. We say the watery diarrhea associated with cholera is a prodigious diarrhea. When you have cholera, you constantly excrete watery diarrhea. It's not like once an hour or once every two hours, it's continuously, prodigious, and if you didn't take in water or electrolytes, you would die of dehydration and many people do, especially young kids who can't take in enough fluids. So preventing dehydration is how you treat this, you don't use antibiotics, you just give people lots and lots of fluids and you have to give them a lot, because as you give them a glass of water, it comes right out again, and you got to keep doing this over and over to prevent them from dying. In some countries they've made a marvelous invention called a cholera bed, they're shown here. I probably don't have to describe them to you, it is a bed covered with a sheet of plastic. You lie on the bed, you're sick with cholera. There is a hole in the middle of the bed, you just lie there with continuous watery diarrhea, there is no point getting up and going to the toilet. In a facility like this, there are many many people with diarrhea, they couldn't have enough toilets anyway, but you would just sit on the toilet all day because you have constant diarrhea. Instead you lie in bed and watery diarrhea comes out of you, goes into this hole and underneath is a bucket that catches the watery diarrhea. Modern medicine, cholera beds. It's actually just a way to collect the diarrhea of course, what you really need to do is give people oral rehydration therapy, it's very effective and you might think, well, isn't that the solution? Well it's not always available, when there are so many people have cholera in a given region that may be economically depressed, it's not easy to find therapy to give people, in particular water or water with electrolytes in it. So you have to give this to people and you have to make great efforts to get it and deliver it to people, otherwise people die. But if you supply oral rehydration therapy, you save their lives. Now not every infection with vibrio cholera is symptomatic, not every infection causes watery diarrhea. You may ingest some vibrios with contaminated water or food and you may be fine, and you could be infected for a couple of weeks and be shedding the organism, potentially infecting someone else, that's called an asymptomatic infection. This is exactly what happened in 2010, you may remember, there was a big earthquake in Haiti.

05:58 The earthquake wrecked the sewage system and so it wrecked many things of course, and the United Nations decided to bring in workers from other countries to help out which was a good thing. They brought in some workers from Nepal, turns out these workers, or a good fraction of them had asymptomatic cholera, they were shedding cholera in their feces. So they went to Haiti and they defecated into the toilet, but the sewage system was broken, so their cholera contaminated the water supply, people in Haiti drank this contaminated water. There was a huge outbreak of cholera, as if they needed that in the midst of the earthquake, now they had cholera. We didn't find this out until a bit after the incident occurred that it was caused by these individuals from Nepal, of course they didn't do it on purpose, but many people were very upset about this and they were mad at the United Nations, but it wasn't their fault.