Fundamental Concepts of Microorganisms

00:01 Hi. And welcome.

00:02 This next series of talks is going to be talking about microorganisms, how they cause disease.

00:09 We're not going to go into excruciating detail about each microbe, that's the province of a microbiology course.

00:17 What we are most interested in here is learning about how pathogens and host interact with each other and how it causes disease, so that's where we're going.

00:28 And this first part is just the fundamental concepts of thinking about microorganism.

00:33 So a very important point, just because you have an infections, just because there is a bacteria within you or a fungus or a virus, does not equal disease.

00:45 In fact, you're all abundantly aware that there is a whole microbiome of microorganism in your GI tract.

00:52 There are more of them inside your GI tract than you have cells.

00:57 Technically, you're infected with all of them and yet, most of the time, they don't cause disease.

01:03 So, important point, infection does not equal disease.

01:06 Instead, the way to think about this is that infectious disease, pathology associated with an infection, is due to a combination of the microbial virulence, things that they do that make them particularly injurious, and there's a big plus there, and the host's response.

01:25 So if we, in many cases leave a microbe alone, it causes no pathology.

01:31 But, if instead we have a very aggressive host response, we can get a lot of collateral damage from all those inflammatory mediators.

01:41 Okay, so, if you keep this in mind, the rest of this is just details. Cool details, but just details.

01:48 Alright, so where we're going the road map for this talk is, this series of talks, is that we're going to be doing fundamental concepts of microorganisms, then we'll do an overview of the different classes.

02:00 Then we'll talk about how microbes get transmitted and the barriers that the host erects to keep them away.

02:08 And then, we'll talk about host pathogen interactions, the pathogenic pathways in infectious disease.

02:14 That's how we're going to generally organize a bit, first, the first topic is fundamental concepts of microorganisms.

02:21 Okay. Well, I'm going to divide the world into nonpathogens and in fact, the vast majority of what's out there, in terms of fungus, bacteria, virus, etcetera; etcetera; etcetera, are nonpathogens.

02:35 So we and them, we go about our daily lives in close proximity to one another, even sometimes, within us, no problems, so they are nonpathogens. And then, clearly, there are pathogens.

02:47 Okay, the pathogens. I'm going to divide it into three. One is high virulent.

02:52 These are guys, these are microbes, bacteria, fungus, whatever, that cause a disease in a normally resistant population.

03:02 So, you and me, healthy individuals without any comorbidities, without anything else going on, and if we get exposed to it, we are going to have a disease in many cases.

03:14 So, influenza, Corona virus, hepatitis, those are all reasonably high virulence pathogens.

03:22 Okay, then there's low virulence.

03:24 And this - these are pathogens, microbes, viruses, etcetera, that will cause a disease only in the susceptible population, that is to say someone who has a incomplete or a none well-functioning immune systems.

03:39 So the very young and the very old.

03:41 You can also have a low virulence streptococcal bacteria that only binds to previously injured heart valves, so the strep virulence, streptococcus virulence, very low virulence, but it has one trick that it knows how to do really well, which is to stick to a diseased valve.

04:00 So that's a low virulence microorganism.

04:03 And, then, there are opportunistic.

04:06 An the opportunistic organisms are those that cause disease in immunocompromised host, so it could be someone who has gotten chemotherapy for cancer or has gotten HIV-AIDS and doesn't have a good CD4 for helper T cell response.

04:21 Or is a transplant recipient and is getting immunosuppression.

04:25 So these are microorganisms that you and I laugh at, you can't do anything to me, they're everywhere and we very easily laugh them away.

04:34 But, in the appropriate host, who's immunocompromised, they can do a world of hurt, and we will talk about that.

04:43 An important concept to think about with pathogens, with microbes that are coming in, is that they all have their favored site of activity or their favored place to go.

04:57 So they have what is called a tissue tropism or a cellular tropism within a particular tissue.

05:03 So, for example, just to make this topic all in current, the Corona virus, only binds to the Ace receptor and it's only expressed at high levels in certain tissues such as lung, that's why it is a predominantly respiratory disease.

05:18 So every organism has a tropism.

05:21 The tropism is about a number of things.

05:25 One, it's kind of the site where it accesses the host, so what barrier does it get across first? So, things that are - do very well at degrading basement membrane, might be able to get in through skin.

05:38 If you have a host, trauma in the GI tract, then we may have tropisms because of the microbes that are in that location, so site of how the bacteria or the virus or the fungus gets into the host is important.

05:58 There are going to be specific receptor expressions.

06:01 I've already talked about the Ace receptor for Corona virus, but certain receptors, such as this surface molecule necessary for hepatitis B to get into a podocytes, only really expressed on hepatocytes and that's why the virus causes hepatitis.

06:16 There's also going to be site specific activation.

06:20 So, what do we mean by that? Well, it turns out the JC virus, the papovavirus that causes a form of demyelinating disease in the brain will only have the appropriate factor for its transcription, the appropriate promoter expressed in the oligodendroglial cells within the brain, and that's the only place that it will set up shop, is in the oligodendroglial cells in the brain.

06:48 And then, there are just favorable growth conditions, so certain fungi like a warm moist place like between your toes, athletes foot.

06:57 Other organisms like a slightly microaerophilic environment, tuberculosis, so it only goes to certain parts of the lungs typically.

07:07 So all of these various components will kind of be the reasons why certain bugs have a particular tropism.

07:15 Why do we care about this? Why do we care about these tropisms? Well, in fact if the bug is extracellular with like many bacteria and fungi, protozoans, and helminths, worms, they're going to be amenable to being regulated, defeated by things like antibodies and by neutrophils.

07:41 Whereas if something is an obligate intracellular pathogen, like viruses like Chlamydia, Rickettsia, like some protozoans and some helminths; antibodies, macrophages, neutrophils are not going to be very effective against that, so the tropism, just at the cellular level is going to be important.

08:04 Important to also know that there are certain organisms that can be switch-hitters, there can be extracellular or they can be intracellular, and these are so called facultative intracellular pathogens and these tend to be the most difficult to clear because they can kind of hide out when they're not in the other environment.

08:22 And certain bacterias such as tuberculosis, certain fungi, certain protozoans, can be facultative either way.

08:29 So other significance of tropisms and the locations, so it's how effective are the bugs going to be in getting to their preferred tissue? Their preferred site? So, if it requires that you have breakage in the skin before you get in, then that will impact infectivity.

08:55 It's also the ability to exit the host and get on into the new host.

09:00 So if you have a tropism, and you're a bug and you happen to live exclusively in skeletal muscle, and the only way that you can get out and get to your next host is through the fecal route, you have to have a way, a connection between the two.

09:17 So the tropism will also impact the ability to get out of the host.

09:22 The nature of the host response is we've already talked about, so if you have an extracellular pathogen, antibody and complements are going to be effective and neutrophils will be effective. But if it's something that's intracellular pathogen, that's going to require the activity of cytotoxic T-lymphocytes or natural killer cells, and in some cases macrophages.

09:42 So, again, what kind of host response were going to have, is another kind of consequence of the tropism.

09:48 And, then, finally, diagnosis.

09:50 If we're - if a bug is in a particular location, we need to actually go to that location to make the appropriate diagnosis, so we need that tissue for sampling.

10:01 We need to be able to culture and to identify the microorganism.

10:07 And, again, if a bug prefers to be in a intracellular environment, wants all the machinery of a cell, that's going to be pretty hard to duplicate in a tissue Petri dish, so that may affect your ability to make the appropriate diagnosis.

10:22 And then, finally, depending on where the bug is hanging out, whether it's in the brain or in the GI tract or in the skin, it's the ability to, for us to deliver therapy to the right location and not all drugs are going to be equally distributed in all of the tissues and we need to think about ways to get therapy appropriately in highest concentration in the right tissue to go after the microbe depending out where it's hiding out.

10:51 And with that, we kind of have a general overview of microorganisms.