All right, welcome back to the microbiology series. In this video, we will be concluding the conversation about the different types of clostridium by talking about clostridium botulinum. Brief overview: here's where we are in the course of our discussion. So, we've already concluded talking about gram-positive cocci, and more recently, if you're going in order, I've been going through the gram-positive bacilli. The first major sub-category of gram-positive bacilli I break down into clostridium, and I've already gone through c. diff, c. perfringens, c. tetani, and now I'm wrapping up the clostridium by talking about clostridium botulinum. So, let's get right into it. Clostridium botulinum is a gram-positive rod. It's an obligate anaerobe. It's spore-forming, which is very important for the diseases that it causes, and it's classically associated with, as the name implies, botulism, and more on that in just a moment. Briefly, here's what it looks like under

a microscope. You can see very clearly delineated rods. These are the gram-positive rods of Clostridium botulinum. Now, by far the highest yield part of today's video, and what I think you need to know for the purposes of in-class exams, USMLE, and COMLEX, or whatever other exam you're going to take, are both the virulence factors, which I'll start with here, but then also the clinical factors, which I'll touch on after we talk about virulence factors. And this is really important to understand because the pathophysiology of Clostridium botulinum is a little bit complex, but once you take a moment and really think about it, all this stuff makes perfect sense, and it's very high yield for exams. So, the major virulence factor of Clostridium botulinum is the botulinum toxin. Now, to be clear, this toxin is a protease, which cleaves SNARE proteins. Now, recall from a previous video, we've already talked about SNARE proteins and how they have a

very important accessory role in neurotransmission, and in the case of Clostridium botulinum, when they cleave these SNARE proteins, what they're effectively doing is preventing the ability of acetylcholine to go from the presynaptic axon terminal into that synapse, right? It's preventing the exocytosis of acetylcholine in the synapse, and when it does that, if acetylcholine cannot go through the neuromuscular synapse, it's inhibiting or preventing the release of acetylcholine, meaning that neurotransmission in these neuromuscular junctions is altered. And so, it shouldn't surprise you to think about this, that if I'm telling you pathophysiology here is net result acetylcholine doesn't work and can't undergo neuromuscular neurotransmission, it shouldn't surprise you to hear that the symptoms of botulism tend to have to do with muscles, right? If acetylcholine plays a key role in

neurotransmission of neuromuscular synapses, but acetylcholine can't work because this toxin cleaves the snare protein that allows it to work. It should make sense to you clinically, the symptoms that we'll talk about in a few slides from now. And so, to really drive this home, what I have here on the slide is a very crude drawing of a synapse. In the synapse, we have acetylcholine stored in a vesicle, and under normal situations, what you have, normal physiology, is what I'm talking about here. The vesicle containing acetylcholine will move into the synapse at the end of that presynaptic axon terminal, and it'll undergo basically exocytosis, in which the acetylcholine gets to the end of the synapse in the vesicle, and then it gets released from the vesicle. And so, what botulinum toxin is doing is it's coming and it's inhibiting that process. It's inhibiting and cleaving snare proteins, which are

accessory in allowing this vesicle to move forward. And so, when we introduce botulinum toxin, we never get the vesicle containing the acetylcholine to the synapse, and therefore we never get the release of it, and we never get neuromuscular neurotransmission. So, that is how the pathophysiology of this toxin connects to the clinical features, which I want to talk about now. Now, I don't want you to overreact. I'm about to put a lot of symptoms on the slide, but this will all make a lot of sense. So, the main clinical features are autonomic symptoms such as xerostomia, which is a fancy way of saying dry mouth, and dysautonomia. There are bulbar symptoms like dysarthria, dysphagia, cranial nerve palsy such as diplopia, mydriasis, lack of the pupils' ability to undergo accommodation. You tend to see a descending flaccid paralysis, descending meaning it starts at the top or the cephalad portion of

muscles that we tend to use more often, and it works its way down. Eyelid drooping, floppy baby syndrome, which is a layperson's way of describing neonatal hypotonia, and GI symptoms. Normally, they start with constipation, can also include nausea and vomiting, and could progress from there. Now, look at these symptoms. There are a lot of symptoms here, but the common theme is that they tend to be neuromuscular. These tend to be connected neuromuscularly because acetylcholine, after all, is what's not working here. And so, if you're thinking about how am I going to remember all these symptoms, one of the stupid ways that I've remembered this is A, B, C, D, E, F, G. So, clostridium botulinum, I think of the alphabet A, B, C, D, E, F, G. So, I know that that might feel a bit overwhelming. Again, there are a lot of symptoms on the slide here, but I want you to take a deep breath because the way that this is going to show up on

exams is usually, I think, usually the test writer is going to go after one of the three subtypes of botulism because although all of these symptoms could technically be present in the various types of botulism. And if you're wondering what I mean when I say types, just hang on, we'll get there in a sec. But there are three subtypes of botulism, and all of these symptoms could technically be present. But depending on whether we're talking about one type versus another versus another, you want to look out for certain symptoms and even more high yield, the treatment is different. And so that's where I think the test writers are going to go because they know that medical students and other graduate health professionals do tend to know the larger symptoms of botulism. So they're going to go after the subtypes and the specific treatments, and that's what I want to talk about now. Now, I've color-coded this for your studying pleasure, but there are three different subtypes.

of botulism. So, when we say botulism, what we're really referring to is the all-encompassing disease, which then gets further broken down and delineated based on the cause. Pathophysiology stays the same, but the cause is different, and the treatment is different. So, we've got infant botulism, we have wound botulism, and we have food-borne botulism. And just as these names imply, infant botulism occurs in infants, wound botulism occurs through this bacteria getting through a contaminated wound, and food-borne botulism is due to the ingestion of the toxin in food. And so, each of these things are classically associated with something which is so high yield for exams. That's what I want to talk about now. So, infant botulism, it's the most common type of botulism, and this is due to ingesting the spores. Now, infant botulism is classically associated with honey or soil, and it's for this reason that you actually are not supposed to give an

infant honey until they're at least one year old. So when you think infant botulism, the first thing you need to know is that cause is spore ingestion, association is honey and soil, and this is really important because when you're taking your exam, if you see honey in the vignette, then they're really pushing you strongly in the direction of infant botulism. Now, like I said, wound botulism is associated with wound infections, so the bacteria gets in a contaminated wound, and this is classically associated with intravenous drug abuse. So just like in your head pairing infant botulism with honey, I want you to pair wound botulism with IV drug abuse because one of the ways that the test writers might hint at this is they'll just tell you patient has a past medical history of A, B, and C, and one of those three things was intravenous drug abuse. And it's something as simple as that that could push you in the direction of choosing wound botulism. And lastly, we have foodborne botulism.

now to be perfectly clear, foodborne botulism is due to pre-formed toxin, which already exists in contaminated food, and then somebody eats the food and swallows pre-formed toxin. So, to be super, super clear, it's not the spore, it's the pre-formed toxin. Usually, the spores get in, and then they germinate and cause the bacteria, which causes the toxin. But in foodborne botulism, pre-formed toxin already exists inside the food, and this is classically associated with canned foods that are poorly pasteurized. So, if you see canned foods on your exam, they're pushing you in the direction of foodborne botulism. So again, I've color-coded all of this for you, but you see honey, it's infant; you see IV drug abuse, it's wound; you see canned foods, it's foodborne. And then as far as the cause, wound obviously is a dirty wound; infant botulism is due to spore ingestion; foodborne botulism is due to pre-formed toxin ingestion; and those

Subtle differences are so important because this is the difference between you getting the question correct and you not getting the question correct. Now, treatment-wise, I told you that there are specific treatments, and I want to take this one step further and just spend 10 seconds on this because it's important. For infant botulism, you would give the botulism immune globulin. For wound botulism, you would give the antitoxin, plus you would do surgical debridement. And for foodborne botulism, you would give the antitoxin, plus you would induce bowel emptying. So, you'd literally give the patient medication that would basically empty their bowels completely so that you could try to get that preformed toxin out. And so, look at these three different types of botulism and appreciate that all of the treatments are different. Infants get the immune globulin, wound gets anti-toxin plus surgery, foodborne gets anti-toxin plus bowel emptying, and it makes a little bit of sense, right?

like if someone has foodborne botulism, you want them to just get it out, so you're going to do bountying. If someone has wound botulism, you're going to do surgery because it came through a contaminated wound. And then infants will need that immune globulin because of their more immature immune system. Stupid mnemonic here, I always remembered that infant equals immune, infant equals immune, and that helped me memorize that that was the one exception where you didn't give the antitoxin and you actually gave the immune globulin. So, that's really it. Here is a summary chart for your studying pleasure. So, your appearance, we're talking about a rod, gram-positive, anaerobic, spore-forming. Virulence factors is the botulinum toxin, which is heat labile. Remember that it cleaves snare proteins, prevents acetylcholine vesicles from undergoing exocytosis and release. If acetylcholine cannot release at the presynaptic terminal, that causes a whole host of different clinical symptoms, which all

tend to be neuromuscular. Remember abcdefg. Those are all of our symptoms. There are three subtypes of botulism that we talked about. Each is due to a different cause, each is classically associated with a different buzzword, and each has a specific treatment. Remember that infant equals immune. All the other ones get antitoxin, and then whether you're talking about wound, you would do surgery, or if you're talking about foodborne, you would have the person empty their bowels. That's it. Good luck.

Clostridium Botulinum

Clostridium Botulinum