Transcribed by Kevin Lin Lecture Date: July 16, 2014

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[Microbiology] [10] [Finish Viruses & Fungi] by [Dr. Boylan]

[10] [Classification of viruses genome]
[Dr. Boylan] So were going to complete the discussion of viruses. Weve already
talked about bacteriophages, the viruses that infect bacteria. Now were talking
about the majority of viruses. Those that infect us, humans, animals, plants, in their
different and many respects (as you have seen already and youll see more today)
than bacteriophage are. One of the big differences of course is, with viruses that
infect our cells, the whole virus gets inside of our cell, gets to the interior. Whereas
the phage, only the nucleic acid gets inside. A big difference between the two. We
talked about how we classify the viruses. Not just teeny-tiny and small as can be,
but we have different properties we use to characterize and put into different
families of different viruses. One of the ways we do this is first looking at the type of
genome that it has. Is it RNA or DNA? Then single-stranded RNA/DNA or double-
stranded? Both types occur. Molecular weight of the genome. Smallpox virus and
herpes virus. Youll hear all about herpes viral infections that cause herpes labialis.
Recurrent herpes infections. Thats a very large virus. It has a very large genome.
And then the parvoviruses has a much, much smaller genome, being a smaller virus.
So we characterize viruses on the molecular weight of their genome. Is it linear or
circular genome? Is it a continuous, it is a one piece of DNA/RNA or is it a
segmented genome. So one genome, but up to 8 different genomes. An example of
that is the influenza virus that has 8 separate segments that are all different from
each other, even though they appear to be just one genome. I think I mentioned,
HIV, they have two strands of single-stranded, positive polarity RNA. The polarity,
positive or negative, for single-stranded genomes only, not for double-stranded. For
the RNA viruses said to have a positive polarity, that means its single-stranded, it
injects its RNA into the cell, and the RNA goes right into the ribosome and directs
translations from the ribosomes of the cell. So thats the definition of positive
polarity with RNA. Recognized as mRNA. If the negative polarity RNA virus,
genome gets in, but it cannot be recognized as mRNA, so it cant do anything
initially. It kind of has to carry its only enzyme with it to begin and eventually cause
the reproduction of new viruses. Well talk about synthesis in more detail in the
course Infectious Diseases. How for DNA, positive polarity versus negative. Once
again, some viruses have single-stranded DNA, positive or negative polarity. That
means that the. Well, if its a positive polarity DNA virus, that means the DNA can
be used for transcription. You know how double helix has two strands of DNA? But
at any one time, only one of the two strands of DNA, or different segments of the
DNA can be transcribed into RNA? So if the DNA of a positive polarity virus is
injected into a cell, theyll be recognized as DNA that can be transcribed. If its a
negative polarity DNA virus, the DNA gets in, it cannot be used for transcription.
More stuff has to go on inside of the cell to enable that to survive and grow and
replicate inside of the cell.

[11] [untitled figure]
[Dr. Boylan] The important part of this slide is shown in the middle. We have all
these different types of viruses. Well talk about them later. You can forget about
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most of those. All they want to point out here is that no matter what the virus is
double-stranded, single-stranded, linear, circular, polarity every virus, when it
undergoes replication inside the cells, has to eventually produce mRNA, messenger
RNA. They all go through that step. So we have RNA viruses, single-stranded, other
positive polarity DNA viruses, double-stranded, single-stranded RNA viruses. They
all go through, they all have to eventually synthesize their own viral mRNA. Without
mRNA, they cannot go on and copy information into proteins, translation. So there
are RNA viruses that dont even need DNA to replicate. Many of them. They dont
need DNA. They already have the information for protein synthesis, which produce
the enzymes that are needed for nucleic acid and protein replication inside of the
cell. So RNA virus can go right to the ribosome. No need for DNA at all. Thats why
for a long time they thought the central dogma was DNA, RNA, protein. Can you
have an RNA virus? No way. It doesnt have DNA . Theres no such thing as an RNA
virus, they thought maybe 30 years ago. Now we know of course there are many
RNA viruses. Some very important ones that cause HIV and other serious infections
in humans. They dont need DNA. The RNA goes right to the ribosome. DNA has the
message in our cells, but the message is carried by the RNA to the ribosome. These
RNA viruses, they already have the message there and they can go right to the
ribosome and direct protein synthesis for the virus itself. But they all have to go
through the stage where viral mRNA is produced.

[12] [Capsid]
[Dr. Boylan] The capsid. All viruses have one. The genome and capsid together are
called nucleocapsid. The capsomeres once again are the different protein subunits
that form capsid. Theyre produced inside of a cell when the virus is replicating.
Different capsid, different proteins. They come together. They self-aggregate and
the capsomeres form the capsid. You can characterize viruses by the number of
capsomeres they have. Some only have about a dozen capsomeres in their capsid.
Others have well over 250 capsomeres. The point being heres another way to
characterize viruses. Number of capsomeres in their capsid.
Capsids role, to protect the genome. DNA or RNA, thats the central part of
any cell as you know. Thats what makes us who we are. So protect that RNA or
DNA from being digested by nucleases or harsh chemicals or other harsh agents
inside the cell that might destroy it. So protect it as long as it can from destruction
by environmental factors. Surround that genome, protect it.
Its a vehicle also for transmission. To get from one cell to another. The
genome is inside the capsid and these viruses replicate inside a cell, are release from
that cell. They infect other cells. So the capsid is the car and the genome is inside of
it and goes from one cell to the other. The vehicle for transmission.
And then adsorption as well. The capsid, the proteins in the capsid help the
virus adsorb or stick to or adhere to our tissue cells, particularly tissue cells. These
are called Viral Attachment Proteins (VAPs), other names given to the proteins used
for adsorption are spikes, peplomers, they bind and these are the ones that
determine the host range. We talked about this before. What is the range of
infection by a particular virus? Is it only humans? Is it humans and dogs only? Or
is it humans and all animals? Thats the host range the virus can infect. Some are
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particular, and only infect humans, and some only infect certain animals. Some
infect many animals, so theyre a bit broader host range.

[screen messing up]
Okay, lets make sure we got this the right way. Okay. This is the next sidelets see if
we have this right. I dont know why its not moving. Maybe Dr. Li can look at it. In
the meantime, Ill look at the slide. Something funny. You got it? Ya. Okay, thanks.

[13] [Classification of Viruses morphology]
[Dr. Boylan] More on the classification of viruses. Morphology. Weve already gone
through some of this. We were talking about phage. The symmetry. The
morphology, the shape or symmetry. Those three terms youll see in literature.
They all refer to the same thing. The shape of the virus. And basically, all viruses
have one or two shapes, with one exception of course. And that exception is the pox
viruses such as the smallpox. Were not gonna say much about smallpox. Anybody
know when the last case of smallpox was in the world? Smallpox has been as you
know eradicated. One of the deadliest killers of all time. Maybe the deadliest killer
of all time. Killed more humans than anything else perhaps in the history of time.
Smallpox virus. But its been eradicated. Hasnt been one case in many, many years.
Actually you dont have to answer that question. It was 1978-1979, the last case in
the world of smallpox. We were able to wipe that out. And well be able to see later
on why that is the case. But only this one viral infection of man, smallpox. And it
was the worst infection of man. One of the worst, anyhow. Top three for sure.
Number one killer probably, of man in the history of time. But we were able to
eradicate it. And there are many very good sound reasons why we could only get to
that of course in infectious diseases. But were not gonna say too much about the
pox virus. The other two morphologies are shown here. Here is we talked about
last week icosahedral or cubicle symmetry. Remember 20 different triangular
surfaces. Its kind of like a soccer ball. When you look at the head or capsid of these
viruses that have an icosahedral or cubic symmetry, morphology, and shape. Once
again, the genome is inside. Its like a sphere or shell.
Then the other morphology is the helical morphology and here you have a
round--. Uhh. The proteins are attached end to end and go around and around and
around and for this helix. Capsomeres joined end to end, spiral staircase. Its just
like a helix, like DNA, only single helix. Or its like a slinky. Have you ever worked
with a slinky when you were a kid? You know those things you put on the steps?
Theyre helix. Anybody have one on them? I do. Heres a slinky right here. Its
really a helix. A single helix. And this is the morphology of this other type of virus.
Helical. So the proteins are end to end around these circumference and they wind
around like that. Another analogy is your telephone cord. Same type of thing.
Thats the way, thats the function, thats the shape of these viruses that are called
helical.
Complex are the pox viruses, shown here.

[14] [Classification of Viruses envelope]
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[Dr. Boylan] The envelope. Some viruses have one more important feature that
others do not. And that is called the envelope. Not found in all viruses, and viruses
that lack an envelope are said to be naked. They do not have an envelope and well
discuss what that is coming up. What is the envelope? A cell membrane-like lipid
bilayer with viral encoded proteins and host cell-derived lipids. The acquired
envelope, well talk about how viruses acquire it. So look at that second sentence
there. The envelop itself. A cell membrane-like lipid bilayer. A lipid bilayer, where
have we seen that before? The cell membrane, of course, is a phospholipid bilayer.
We havent talked much about the nucleus because thats not found in bacteria, but
the nuclear membrane is also a phospholipid bilayer, with proteins and other things.
So the membrane-- the envelope itself has a phospholipid bilayer, derived from the
host cell. The cell this virus is growing in or replicating in gets its envelope, if it has
one, from the host cell. Either the cell membrane of the host cell or the nuclear
membrane of the host cell depending upon the type of virus it is. As well see later
on. Okay so we have the envelope with the cell membrane derived from the host
cell membrane. And then in the membrane itself, this envelope are proteins as well.
And the proteins that are found in the envelope of an enveloped virus are directed,
produced by virally encoded genes. So the genesthe proteins themselves in the
envelope are directed, not by the host cell, but by the viral genes themselves. So
specific to the virus. So envelope has two parts. A membrane thats derived from
the host membrane, nuclear or cell membrane, and proteins embedded in it that are
there because of the genes in the virus itself. Virally encoded proteins.

[15] [Envelope composition]
[Dr. Boylan] Lipids, proteins. So here we have an envelope. This shell, this circle
outside is the envelope of the virus. Inside, we have the nucleocapsid. Heres the
capsid in there, inside of that of course is the genome. But were looking at this
envelope and you dont get too good of an idea, but this is sort of the bluish-area
here that would be a phospholipid bilayer thats produced around the nucleocapsid
of the virus that has an envelope and youll see these other components, the white
stuff or tan, yellowish are the proteins. Are the proteins found in the envelope, so
once again, this blue stuff here, the phospholipid bilayer of the envelope comes from
the host. These proteins are virally encoded. Not host encoded, not from the host
cell thats infected by the virus.
The matrix proteins are proteins that help the capsid bind to the envelope.
Matrix proteins. So thats there in there somewhere. The external proteins that we
see here. Here, and here. Are outer proteins and they are glycoproteins. They have
sugar residues in them. They are the spikes. And those are the proteins, these spike
proteins, the peplomers, the VAPs. Those are the, these proteins in the envelope, are
the ones in these viruses that determine what cells the viruses will attach to. So
these are the proteins that look for receptors on our cells. The herpes viruses, they
detect receptors on our tissue cells in our oral cavity, on our lip, etc. and bind to
them. So when you have an enveloped virus, the adhesion of the enveloped virus to
our cells is mediated by the proteins in the envelope. When you have cells sorry,
viruses without an envelope, the proteins that mediate attachment are in the capsid
itself. Theres no envelope. So once again, naked viruses the proteins in the capsid
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determine adhesion to ourselves. Enveloped viruses, the proteins in the envelope
determine the cells that the virus will attach to. Embedded lipid bilayer. Peplomers
are the names for spikes. Hemagglutinin spikes of flu virus. Were gonna talk a lot
about the flu virus in the next course. Influenza virus and the two types of spikes it
has. Hemagglutinin spike is one. Thats the one involved in adhesin of the flu virus to
ourselves. And another important spike, once again glycoprotein (spike are
protein), is called Neuraminidase of influenza virus. These are the two important
spikes of the flu virus and youll see the importance of them in influenza and
pandemics and epidemics. This is one of the most unusual viruses in a way, it can
undergo changes that cause these worldwide pandemics and outbreaks of
epidemics. It can change its hemagglutinins and neuraminidase and other proteins
in it. And that enables us, it to spread worldwide sometimes. And of course, these
outer proteins, spikes would be antigenic. And they have a little about immunology
-- that means that these spikes, these proteins out here are the ones that initiate an
immune response to them. One of the host defenses are antibodies, will be
produced against these antigens of the surface of these virus if they have an
envelope.

[16] [Is virus enveloped?]
[Dr. Boylan] How do you determine if the virus is enveloped or not? Okay, heres
the key. Youre given an example, sorry. Youre given an unknown test tube with
viruses in it that youre told. And you asked the question is it an enveloped virus
or it is not? That is, does it have an envelope of phospholipid bilayer? Or is it just a
virus that has the capsid, no envelope? So can you determine easily which one it is?
Well, the way we do this iswell, once again, think of the envelope. Thats the
envelope thatphospholipid bilayer, proteins, spikes. Lipid. What we do is we use
things to try to dissolve the lipid in the lab. So we have these viruses in a test tube.
Add a little something, we often use chloroform. That will dissolve the lipid in the
membrane. These viruses will lose their envelopes because of solubilization of the
envelope. Whereas this chloroform will not have any effect on the naked viruses
because the capsid is a nice, hardy proteins surface only. So then you, lets say-- the
enveloped virus you add chloroform. You then clear them of the chloroform, purify
them, separate them from the chloroform and see if they will now still infect the
cells they did before. So in other words, you know with the envelope, they will
infect certain cells. The mouse cells. You treat them with chloroform. They can still
infect-- Can still infect mouse cells? If they cannot, well that means their envelope
has been digested away, along with their spikes and that was an enveloped virus. If
it was a capsid-only virus, no envelope. You treat them with chloroform, wash away
the chloroform, add those viruses to the same cells they infected before, they will
still infect those cells. So thats one of the ways we, among other ways, can easily
distinguish between enveloped and naked viruses in the lab. Fairly easy anyhow.
Once again, just think about the envelope. Its lipid. Dissolve it away. All these
hemagglutinins and neuraminidase and other spikes will be lost. These are spikes
that are used for determining of the host range and the adhesins to our cells.

[17] [Naked Viruses - properties]
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[Dr. Boylan] So naked viruses. Just once again, think of the difference between the
two types of viruses. Viruses that are naked, that have only a capsid surrounding
their nucleic acid, so theyre hardy proteins. All those capsomeres. Tightly bunched
capsomeres. Whereas an enveloped viruses has the flimsy phospholipid bilayer.
Much more sensitive to environmental factors that want to destroy it. So lets say
some differences between these two types of viruses. Naked virus, the protein is the
component of the capsid. It is stable to the follow conditions. Naked viruses will not
be destroyed by temperature, acids, proteases, detergents, and drying. Well
sometimes, there may be some proteases of course, but since it is protein thats
much more resistant to proteases and these other environmental factors shown
here than our enveloped viruses. When theyre released from cells, when they
replicate inside of cells, these naked viruses lyse the cell. So they grow inside the
cell, like the lytic bacteriophage. They grow inside the cell and then they destroy the
cell. They dissolve the host cell and they are released by-- when they lyse the cell.
So these types of viruses are called cytolytic viruses. And well see with the
envelope, thats not the case. Enveloped viruses kind of bleb out one at a time. They
dont destroy the whole cell in a second. As we do see with these types of virsues
here that just explode out of the cell.
Consequences. Can be easily spread. Hardy capsid covering. On fomites,
that is, inanimate objects. Everything except for all of us who are sitting here, we
can say are inanimate objects. The desk, the paper, so if theyre lodge if you cough
them up or touch these inanimate objects, the fomites. They can stay there in this
environment for a longer period of time than enveloped viruses because they dont
dry up as fast. Theyre hardier. Hand to hand, by dust. And well see that later on
when we talk about transmission of viruses, that these naked viruses are much
more readily transmitted because theyre hardier and theyre more stable to
environmental factors shown under properties there, than the enveloped viruses
are.
Can dry out and retain infectivity. Can survive the adverse conditions of the
gut. Can be resistant to detergents and poor sewage treatment. So sometimes they
survive in even when you try to destroy them by sewage treatment plans.

[18] [Enveloped viruses - properties]
[Dr. Boylan] In contrast, enveloped viruses have lipids, membranes, proteins,
glycoproteins. Environmentally labile. Sensitive. So theyre easily destroyed by
acids, detergents, drying, heat. Modifies cell membrane of host during replication,
we talked about that. And they are released by budding. Well see examples of that
later, too. They bud out. Here, theyre formed inside of a cell. Maybe 50 to a 100,
200 viruses. And instead of lysing the cell, they kind of push their way out of the
cell, like a little bud. And when they push their way out of a cell, they take along
with itthats when they pick up the cell membrane of the host cell theyre
infecting. How do they get the phospholipid bilayers in their envelope? When they
push out gradually, easily out of a cell. They take out with them that phospholipid
bilayer of the cell membrane of our cells. It surrounds them. Are re-embedded with
these protein spikes we talked about before. So they dont destroy the cell in the
way that naked viruses do.
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So the lipid, they must stay wet to survive outside. Drying is-- theyre very
sensitive to drying and desiccation. They dont survive well in the GI tract, where
there are a lot of enzymes and lipases and bile and other things that can easily
dissolve the membrane, so they dont survive there long. They spread in large
droplets, secretions, organ transplants, and blood transfusions. Do not need to kill
the cell to spread. So once again, they dont have to lyse the cell as we saw with the
naked. They can spread, they can come out one at a time, or 20 at a time. Different
sites of the cell and infect other cells over and over and over again without killing
the cells.

[19] [Additional information about viruses]
[Dr. Boylan] Additional information about viruses. The three big properties. If you
want to identify-- we talked about up to this point, about how we classify viruses
according to their genome properties and whats found in their capsid or their
envelope. The three big properties of viruses are the type of nucleic acid. It is a
DNA virus or is it a RNA virus. Thats the first main question you would ask about a
virus. Then, is it enveloped or is it naked? Thats the next big question about all
viruses. And the third is the morphology, the symmetry. Is it icosahedral or helical?
So among other properties we already discussed the viruses have to help classify
them, these are the big three. Is it DNA or RNA? Naked or enveloped? What kind of
morphology, icosahedral or helical? Later on well talk about herpes and hepatitis
and we will ask you to remember for not all of them, but certain ones, the big three
properties, at least of these viruses that cause infections that are much more
important to you in your practice.
Cytolytic viruses, once again, those are the ones that are ordinarily-- are
naked. Lyse the cell, cytolytic. And I know next week when Dr. Tierno comes here
to talk about antibiotics, he will say that some of these are cytocidal. Bacteriocidal
means these are antibiotics that actually kill bacteria. Whereas others are
bacteriostatic and dont kill, but stop the growth of bacteria. So he uses -cidal.
Hes gonna talk about the fact that those are antibiotics like penicillin and others
that destroy the bacteria. And not just stop it from growing. So some are cytolytic,
those are the naked ones. And the budding ones, the ones that bleb out are the
viruses that have the envelope. And we already talked about some of these, the
temperature, salt, pH. Viruses are sensitive to low pH, the extremes of pH, radiation,
ether - that would say envelope viruses would be sensitive to ether, that dissolves
lipids. Not to antibiotics though. Not to antibiotics. Antibiotics are drugs that are
used for treatment of bacterial infections. Now Id like to contrast those antibiotics
to antiviral agents, well talk about also later. These are chemicals that we use to
treat viral infections. I dont like to call them antibiotics. I dont like to call them
antibiotics. I think that term should be used just for those agents used to kill
bacteria. Whereas antiviral agents are used to treat infections like herpes, acyclovir,
HIV, AZT, and many, many others well talk later on. There are indeed antiviral
agents that inhibit the replication of the virus inside of our cells at different stages of
viral replication. I like to call them antiviral agents and not antibiotics. Detergents,
once again, those viruses that have an envelope would be much more sensitive to
detergents that would solubilize them. Bleach is good for all viruses. Formalin also
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very good virucides as well, kill viruses. Bleach is good. 0.5% bleach will destroy
even capsid, even naked viruses.

[20] [untitled figure]
[Dr. Boylan] So in summary, you can look this over. Ill go through it rapidly
because I think weve already gone through most of these points. Viruses are
obligate intracelleular parasites, which are metabolically inert, can replicate only
within living cells. Genome DNA or RNA, protected by the capsid. Nucleocapsid is
one of three is one of three, icosahedral, helical, or complex. Complex, only pox have
that symmetry or morphology. The enveloped viruses. No envelope, naked. The
peplomers or spikes are glycoprotein extensions from the envelope or capsid that
play a role in adhesion or attachment, once again. Theyre important for that
purpose. They determine the host range, what host a virus will infect. Its got to
find something on the surface of our cell. Every microbial agent, viral, bacterial,
fungal, has to find something in our body to adhere to, to initiate an infection.
Otherwise, its gonna be washed through our body and be lost from our body. So
eventually they got to find the right receptors on the right tissues in our body that
they can adhere to. Then they can infect the cell and replicate. And I mentioned the
big three. Were not going to go through all the families and genera and species of
common names are routinely used when describing viruses. What I mean by that is
you get herpes viruses. There are hepatitis viruses. There are neurotropic viruses,
things like that. Were not going to go through all the different genus and species
names of viruses as we will with some of the bacteria later on that cause infections.
And okay, I think thats about it. So thats about the big overview of viruses. Youll
see a little more about them in the course Infectious Diseases.

[21] [untitled figure]
~note: virus names in the [brackets] is the one he is pointing at.
[Dr. Boylan] Once again, here you see here, DNA viruses. Heres the pox virus,
unusual virus. Heres a herpes virus. Causes herpes labialis, cold sores. You have to
be careful you dont get them from your patients, of course, by wearing gloves. So
heres one, this virus [herpesvirus] would have an icosahedral symmetry, and it has
an envelope around it. Heres one that haspapovavirus, well talk about thatyou
dont have to remember this now, but just know there are indeed differences in this
case, the morphology of viruses. Heres papova, its a naked virus. Heres a naked
virus [adenovirus] that has, well see later on, some unusual protein spikes in its
capsid. Adenovirus. Adenoids. Can cause common cold, conjunctivitis, and some
other infections. And here we have some RNA viruses. You see some unusualthey
call this [filovirus] a helical morphology, essentially, but this here [paramyxovirus]
is a helical here. Something like this [orthomyxovirus] represents a helical
morphology. Whereas here [retrovirus] we have icosahedral morphology. An
envelope virus. Here [reovirus] is an RNA virus that does not have an envelope.
And here [rhabdovirus] is an unusual one. Couple unusual ones, rhabdovirus that
causes rabies. Its said to be bullet-shaped. So some do have indeed unusual
variations of those two basic structures of viruses. But even these shown here,
either icosahedral or helical. So well talk about most of these later on. You dont
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have to remember them now, but there are variations in size, shape, and nucleic acid
content, and naked or enveloped viruses. General properties of viruses.

[FUNGI]
[1] [Fungi - Properties]
[Dr. Boylan] Any questions on viruses?
Lets a take a two second break. And okay well talk about[laughs]. I think Ill
finally be able to finish a particular topic on the day Im supposed to. If I goI wont
go too fast. So, well talk about--. influenza, mono, hepatitis, common cold, all these
are really interesting viruses, why do they call them different infections? They have
different adhesins, they replicate slightly differently in cells, HIV, different, what we
call, replication cycles. So all that, well go into more detail later on. But one again
they infect the cell, they infect the cell, the inject the whole virus-- uncoating has to
occur to release the genome of the virus and then it takes over the cell. It takes over
the whole metabolic machinery of the host cell. Everything that host cell was doing,
our cells, stops. And the virus begins to direct the production of more viral enzymes
for nucleic acid and protein production. And eventually replicates itself to hundreds
of progeny inside the cell and either lyses the cell and is released, or blebs out or
buds out one after another to pick up the envelope, if theyre an enveloped virus.

So fungi, third type of microbe. Weve talked about bacteria and viruses. The fungi.
And just briefly talk about the properties of them.

[2] [Mycology]
[Dr. Boylan] The study of fungi is called mycology. Study of myco-, of fungi. And
I remember I was waiting on a train platform, coming in to school one day, and I had
my briefcase in a binder. And on the binder, it had the word, mycology. So some
guy was standing next to me, mycology. So what is that? And I said thats the study
of fungi. He said, why dont they called it fungiology? I thought, I think I would have
laughed too if I had to say I study fungiology, but they call it mycology. It means
the same thing. Study of fungi. Singular, fungus. Fungi, some people say fun-guy.
Im a fun guy. Youre fun guys. But these are Fungi [fuhn-jahy]. But both work. I
guess I dont [dislike] anybody if they pronounce it fun-guy.
There are well over 100,000 species. Only about 100 are pathogenic for man. And
12 cause most of human infections. We have two great lectures in the course
Infectious Diseases by guest lecturer on these infections. Lets get an overview of
types of infections and the properties of fungi. They have a nucleus and other
cellular components. So these are indeed eukaryotes. Yes, they are microbes, not
like bacteria, not like viruses, they are true eukaryotes. They have nuclear
membranes, they have mitochondria. They have all the intracellular components
that our cells have because we are eukaryotes, too. But they are microbes.

[3] [General properties of Fungi]
[Dr. Boylan] Theyre eukaryotes . The cell membrane is called the plasmalemma.
The cytoplasmic or cell membrane of fungi is given that term. Plasmalemma. And it
does have ergosterol, a sterol, in it. Remember, bacteria dont have sterols in their
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cell membrane except for Mycoplasma. But other bacteria do not have sterols in
their cell membrane, but fungi do. They have one called ergosterol, shown here.
And thats very important because thats going to be, as well see, one of the targets
that were going to attack with our antifungal agents to treat fungal infections. This
unusally sterol found, not in our membranes, but only in the membrane, the
plasmalemma, of fungi. Unique to fungi. And well see later on it binds these
antifungal agents that are used to treat certain fungal infections. So the fact that this
plasmalemma here, this membrane, phospholipid bilayer that fungi have has an
unusual sterol, ergosterol. The site of attack for many antifungal agents, agents used
to treat fungal infections. No cholesterol though, only ergosterol. And no other
living cells, except for fungi have this unusual sterol, ergosterol.
The cell wall is made up of chitin. And the chitin in the cell wall has our
friend N-acetylglucosamine, which is also found in peptidoglycan. But as we know
peptidoglycan has this sugar, we well as muramic acid. In the cell wall of fungi, they
have N-acetylglucosamine, but they also have glucans. Glucans are large polymers
of glucose. And well see, thats anotherglucans are another target (we wont
discuss in this course) for antifungal agents. These glucans. We dont have them in
our cell. We dont have cell walls. So whenever youre trying to treat a viral,
bacterial, or fungal infection, what is unique about these microbes? What is
something we dont have in our cells? And then that might be an Achilles heel for us
to try to find something to attack that unusual feature. Stop them from growing or
stop them from replicating and do that without harming our cells because we dont
have that component in our cells. Cant always do it 100%, but thats one of our
goals.
Some have a capsule, both antigenic and antiphagocytic. Thats the most
important role of any capsule, bacterial or fungal. Antiphagocytic. Protects them
from being phagocytized by our phagocytes and our macrophages and our
monocytes, dendritic cells. Protects them from that. The capsule that surrounds
them helps them slip away from these phagocytes. So they are not digested and
destroyed. Antiphagocytic. The most important role of a capsule.
Microtubules and microvesicles are found--. The microtubules shown here
are kind of like the cytoskeleton of the cell. We have a skeleton, bacteria do not.
Kind of like the cytoskeleton, help them maintain their shape. And microvesicles are
fragments of cell membrane, actually, that bleb off from their actual membrane and
are found throughout the cytoplasm of the fungal cell itself.

[3] [General properties of Fungi-growth]
[Dr. Boylan] Theyre aerobic. Fungi are easy to grow in the lab. The term we use
for bacteria that do not grow easily in the lab, they require a lot of supplements like
vitamins, sometimes, and serum, and a lot of good nutrients we call those types of
microbes fastidious. Fungi are not fastidious. They grow very readily as shown
here. Here you see them growing on a Petri plate. And here we see well isolated
colonies of a fungus. And on this simple, this very simple medium, called
Sabourauds medium to grow almost all the fungi. And all it is is just one sugar,
glucose, and peptones. And peptones are digestive proteins, so amino acids. If you
look at the formula of other media used to grow bacteria, say theres a list of maybe
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10, 12, Dr. Li works with some with 25 ingredients in them. You dont need that for
fungi. Simple medium. Glucose, peptones, thats enough. But also anotherthis
medium, Sabourauds, has a low pH. pH is about 5. And yeast will grow very well at
this acidic pH of 5. Most bacteria do not grow well at this acidic pH of 5. There are a
couple exceptions. So this pH, this low pH of this medium, fungi can still grow at
that pH. Bacteria are inhibited from growing. Most bacteria. So its kind of what we
call a selective agent. Youll hear that term more when Dr. Saxena gives his lectures.
Its a selective agent in the medium itself, the low pH. It selects for the growth of
fungi that can grow at pH 5, but it selects against the growth of bacteria. Thats the
advantage there? Well if you have a fungal infection, here and there in your body.
And you get a sample of there are going to be these fungi, but also bacteria. They
get to the scraping of that lesion, you streak on this plate, Sabourauds media. If
there are bacteria there, they wont grow well. Whereas yeast will grow well. It
helps to identify them that much readily because you select for their growth by the
low pH and select against the growth of bacteria that might be there.

[5] [Comparison of fungi and bacteria]
[Dr. Boylan] Some differences between the two types of microbes. Fungi are
larger. Fungi are eukaryotes. Cytoplasm, once again, eukaryotes, mitochondria, and
ER, all those other things we saw on the previous slide. Sterols are present in fungi,
absent in bacteria except for Mycoplasma. Chitin is the component of the cell wall.
N-acetylglucosamine and glucans. Peptidoglycan, you know that upside down,
inside out because we discussed that many times in previous lectures. And spores.
Sexual and asexual spores are used for reproduction in fungi. Remember I made the
point over and over again that in bacteria that are spore-formers, the Bacillus that
aerobe, and Clostridium, that anaerobic bacterium, those are the two Gram-positive
rods that form spores. They are spore-formers. They do that for survival. They can
sense theyre running out of nutrients so they form a spore, an endospore for
survival that will [help them] survive under very harsh conditions. Whereas with
fungi, they produce spores one after another and another spore. More and more
and more numerous spores to reproduce, not for survival, as in bacteria.

[6] [General characteristics of fungi]
[Dr. Boylan] They love humidity. And if you ever have a damp basement or a damp
room, its humid, get a dehumidifier. Itll save you conditions such as this because
fungi can grow on almost anything. And once again, to grow in the lab, we use sugar
and peptone. They can grow probably here on wallpaper or maybe the glue. A very
humid environment enables them to grow on almost anything. And thats why
many people have spent thousands of dollars trying to get rid of mold and infections
in their homes because parts of their homes were very humid for a long period of
time. Especially in the summer, and these fungi just loves to grow. I have two
dehumidifiers in my basement, one of them in my tool room. I dont want my toys to
get moldy. So I have two of them going all the time in the summer. It makes a big
difference in the humidity in the room. I remember when my daughter had to-- one
of my daughters used to do her laundry. And shed get her jeans. And she didnt
want to put them in the dryer, so she would leave them out, put them on the ironing
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board and couple days later and they would finally be dry. And I remember a
dehumidifier one time, and the first time she came down about two hours later and
her jeans were already dry. And she was amazed that it didnt take two days
because the humidity in the environment have kept her jeans from drying up. So the
dehumidifier is a great thing to have. And she told her friends what had happened
and they all told their parents to get dehumidifiers, too.

Another property about fungi is theyre dimorphic. They grow and appear in two
different shapes as either yeast or mold.

[7] [Yeast form]
[Dr. Boylan] Heres a yeast form. Single cells, unicellular growth. Theyre
spherical. Larger than bacteria. Theyre about 4 micrometers. Even larger than
that. The ones I have grown are 8 orlarge diameter. In other words, larger than
bacteria. They divide, the yeast divide by budding. And here we see one cell. This is
the one yeast cell going to divide into two. And rather than binary fission, growing
larger and dividing right in the middle, it sort of blebs out a bud. And thats gonna
be, its called a bud. Another name for it is a blastospore. This newly forming cell
here. A bud or blastospore. Thats the yeast form. Single cell.

[8] [Mold form]
[Dr. Boylan] The mold form is multicellular. These are hyphae, we call them.
Filamentous stuff. What you see here on lower part [picture] heres a tomato. What
you see here on bread these are harmless fungi, but these are indeed fungi. These
are the mycelium of the fungi, up in the air, whereas some of the mycelia, of course,
are anchored in the tomato, anchored in the bread for the nutrients, but then they
start to grow and they form these spores that project up in a filamentous form
shown here. And they all mingle with each other to form what is called a mycelium.
So here you see on these tomato and bread you see mycelium of fungi. Aerial
mycelium are the ones you see. The Vegetative mycelium are the ones that are
embedded into the food to get the nutrients for the fungus to grow.
Pathogenic fungi in general they grow in yeast form in tissues when theyre
causing infections in us. They all have these two morphologies. When theyre
causing infections in us, and well see many of those infections later on, they are
usually in the yeast form. When theyre out in the environment, out in the air, out in
the deserts, out in the soil, they are usually in the mycelial form. In the mold or
mycelial form. Now we get exposed to the mold, then they change their shape to the
yeast form inside of us, and then they cause infections.

[9] [Histoplasma capsulatum]
[Dr. Boylan] Just an example of one type of fungus well get to later on. Mold and
yeast form. Heres the yeast form of it. Heres the mold form, parts of the
filamentous. Well talk about the saprobic phase, that means outside, living in the
wild, in wood or soil. It forms these. Were infected with these disease phases,
the mold form, which converts to the parasitic phase, the yeast form, in us and
begins to replicate in our lungs and cause serious pneumonias.
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[10] [Fungal reproduction -Asexual]
[Dr. Boylan] Reproduce sexually or asexually. Asexual by asexual spores called
conidia. Asexual spores, some are large, some are small. Named according to how
these spores develop in the fungal cells. Chlamydospores, weve already seen.
Thick, swollen, roundIm sorry. Chlamydospores are thick, swollen, round cells
well see in the next slide. Blastospores youve seen before. These are the buds.
Arthrospores are thick, rectangular cells. So those are different types of asexual
spores called conidia. If theyre large, theyre called macro-, if theyre small theyre
called micro-. Okay.

[11] [Asexual spores]
[Dr. Boylan] Heres just examples of some of them. Heres for example, the
rectangular cells, spherical cells. Macroconidia, microconidia. This is blastoconidia,
youll see these words here. Pseudohyphae, forget about that now. Well get back to
that pseudohyphae because that occurs in only one type of fungus, which is
important. Candida. Forms oral infections. So these are just examples of many,
many, many morphologies of fungi.

[12] [Fungal reproduction - Sexual]
[Dr. Boylan] They can undergo sexual reproduction where they actually mate.
They can mate. Male, female, they exchange genes. They come up with new spores.
So both sexual and asexual reproduction can occur in their eukaryotic cells, fungi.
Fungi Imperfecti, you may have heard that term. Only asexual reproduction has
been observed. So as far as we know, some fungi, we have not been able to see
whether or not they undergo sexual reproduction, shown on the top of this slide. So
these are called Fungi Imperfecti. We know they undergo asexual reproduction. We
have never been able to detect sexual reproduction.

[13] [Antifungal agents]
[Dr. Boylan] Antifungal agents work by either affecting the fungal membrane or
attacking, affecting the fungal processes. And Ill wind of with this slide and thats as
far as we have to go

[14] [Antifungal agents]
[Dr. Boylan] And this slide hereits as far as we have to go. Forget about the rest.
I know were going to cover the other few slides in the next course. So I want to
focus on this as being the last slide youre responsible for, in the lecture on fungi.
Antifungal agents. One class its a class, and so examples of it class and
the mechanism. How do these agents kill fungi. One class youre gonna use these a
lot. Amphotericin B and nystatin to treat your patients fungal infections like thrush
and oral infections. Polyenes such as these two shown here, nystatin, remember
that particularly, bind to ergosterol. Remember this is the component, sterol found
only in the plasmalemma. Not found in our cells. So polyenes antifungal agents find
to ergosterol. Upsetting the cell membrane, of the fungi, leading to its destruction.
And stuff just begins to flow in and out without any direction at all. So just binding
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to the ergosterol. It doesnt bind anything in our cells because were not affected by
the nystatin, amphotericin. But it binds to ergosterol, upsetting the metabolism,
functioning of the membrane, leading to the cells death.
Azoles inhibit ergosterol synthesis. So no ergosterol being synthesized by
fungi, theyre not going to produce the usual plasmalemma, theyre going to die. 5
flucytosine as well, inhibits DNA and RNA synthesis. Particularly in fungi, although
in some other cells, too. And griseofluvin inhibit microtubule assembly. So
microtubules, remember the sort of cytoskeleton of fungi needed for the fungi to
maintain their shape. If the skeleton, the microtubules are not produced, theyre
going to collapse and theyre going to die. So we hone in on particular components
of a microbe to try to disrupt them, prevent their synthesis, and leading therefore to
a good treatment of the microbes to try to cure infections they cause.
So well just stop here as far as fungi go because I know were going to cover
the rest of it in Infectious Disease. Okay. Thank you.