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Transcribed by Amit Amin November 11th, 2014

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[Infectious Diseases] [4] [Streptococcus] by [Dr. Boylan]

[13] [Deep Abscesses]

[Dr. Boylan]OkGood afternoon. So we are going start back talking about the

Staph Cocci, remember we said were are going to begin infection diseases by talking

about gram positive cocci. The staphylococci, we have already started that and nextwill be the streptococci. They say you will see more of these types of infections

when you practice after dental school. Maybe a lot of patients here you will see in

the next couple years as well. In the VA I know they have a lot of patients with staph

and strep and skin infections and other types of infection so its good to be familiar

with them. Talking about S. aureus, is the microphone ok? Its little high. S. aureus 2

types of infections generally: abscesses, which we have already gone through, and

toxemia or toxicosis. More due to the toxins produced inside or outside the body,

growing somewhere outside the body. They can form toxins that can make us sick

and they call them toxications. We were finishing up taking about the abscesses and

once again I have something highlighted in red an italicized and underlined so its

probably pretty important for you to remember. Any access in any organ or tissueshould make you think of S. aureus. Its not always the case but staph is not just on

the skin, but also internally. If it gets into the blood stream it can bind to bone, brain,

other organ and cause serious abscesses and destroy those organs and lead to death.

Osteomyelitis, build of the bone can be cause by S. aureus. Arthritis can be causes by

S. aureus. Endocarditis, heart infects, and brain infections also can be caused by S.

aureus. Endocarditis, acute endocarditis, rapid onset infection of the endocardium of

the heart is found in IV drug users people who share needles when the inject

themselves with drug. They wipe of the tip of the needle but there is a little bit of

blood there, and if they have S. aureus even in small amount on the tip of the needle

they can transmit it to the next person who uses the needle so we see that quite a it

today. IV drug abuse can cause endocarditis due to S. aureus.

[14] [Other virulence]

[Dr. Boylan]We talked about various others factors of Staph. The toxins, the

cytolytic toxins are obviously meany. Hemolysins as you know are toxins that

destroy red blood cells, but these hemolysins they lyse blood cells hemo-lysin, but

they can also lyse other cells in out body like epithelial cells and due a lot of damage

that way. Membrane damage, they form pores in the cell membranes of epithelial

cells and RBC. Pores, and as a result everything in the cell can leak out, there is no

control of what gets into the cell or out of the cell when pores are formed when

these toxins bind to membrane components leading to lysis of the cells. Leukocidins

lyse white blood cells.

[15] [Toxin Diseases]

[Dr. Boylan]Lets talk about the so called toxemias or toxicosis or toxic diseases.

The diseases caused by S. aureus because of the toxins they produce. Scalded skin

syndrome or sss, toxic shock syndrome, and food poisoning. These three toxemias

are a result of production of super antigens. Actually what it is, is the toxins these

infection caused by different strains of s.aureus not every s. aureus can cause all of

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these things we have talked about up to this point, but different strain we come in

contact with. We harbor different strains of s. aureus in our body and they have the

ability to produce different types of toxins. So these toxins that cause toxemias act as

super antigens, and we discussed this in immunology what super antigens are as

opposed to just regular antigens?

[16] [Super antigens]

[Dr. Boylan]We will se that here. As you know most antigens when our phagocytes

our macrophages our neutrophils engulf bacteria and they take them in form the

phagolysesome and then they are lysed, these cells are called APC. They then show

the bits and pieces of the bacteria they just digested on the surface of the cells right?

So they present the antigen on the surface of the cells are called APC, and they notify

the rest of our immunes system to come into action to come irradiate these cells and

bacteria. So most of the time antigens are presented on the surface of neutrophils or

macrophages, but these super antigens don't act that way. These super antigens

these exotoxins produced by S. areas are not presented on the surface of these cells,

but what they do is they bind surface components of the APC, I wont go into MHCnow, but the surface components of the APC to t-cell receptors on t cells. So they act

as kind of a bridge these super antigens produced by s. aureus. This is the way they

work rather than being digested cleaved and presented, they bind right away these

two types of cells. So they are not processed by the APC they bind to the APC and T-

cell as a result there is non-specific activation of t-cells. This is where the danger is

in many of these antigen especially the toxic shock syndrome. They cause the

production or they activate up to 20 percent of our t cells. Ordinarily in the course of

an infection 0.01% of our t cells are activated come into action and use cytokines,

but up to 20% and this cell has a massive pouring of cytokines in the blood stream

as a result of this super antigen activity. The cytokine release how they will circulate

and we will see that that can cause a lot of damage especially with toxic shocksyndrome but also with other toxemias caused by s. aureus when these super

antigens enter the blood stream. DIC- disseminated intravascular coagulation. Blood

clots form interrupting the flow blood, hypotension, and shock and even death and

organ failure. So these can be very potent toxins these super antigens.

[17] [Staph toexmias-1]

[Dr. Boylan]Here is one that is not quite as dangerous as the others that we will

mention, but this SSS toxemia I mentioned before caused by s. aureus. The primary

host are young children who some how come in contact with strain of s. aureus that

produces exfoliation. SO the super antigen is called exfoliation and what it does is

exfoliate the epidermis dead skin from living tissue. What also this enzyme does isseparate the layers of the skin and causes this blistering (Bulla). Thatsthe way this

exotoxin works separate the layers of the skin. About 20yrs ago about a mother who

brought her son into a hospital in Westchester because he looked similar to this

child here, he had blisters all over his body. When they saw this child they called the

police and had the mother arrested. They thought the mother had poured scalding

hot water on this child and thatswhat lead to these blisters that you see here, thats

why its called SSS, it looks like hot water was poured on skin leading to this

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condition. She was in jail for one night if I recall and then somebody figured that no

it was not the result of child abuse , but due to the child having this toxemia cause by

s. aureus.

[18] [Staph toexmias-2]

[Dr. Boylan]Another one produced by s. aureus strains is toxic shock syndrome.The toxin itself is called toxic shock syndrome toxin (TSST-1). Symptoms, I want you

to remember these thatswhy I spelled them out here. Fever and rash are

characteristic of this toxemia. Rash especially on the hands an feet. Toxic shock

syndrome manifests itself with a sudden onset of fever, chills, vomiting, diarrhea,

muscle pains and body-wide rash. Why a body-wide rash? Well we will see other

toxemia as well have body wide rash, and its because all these cytokines are in the

blood stream throughout the whole body and they are doing damage, disrupting the

blood vessel activity causing rash to occur. Hypotension and mucous membrane,

multi-system involvement, and later desquamation also like we see with SSS are a

result. This is not as prevalent now as it was second half of the seventies, all of a

sudden this particular infection which was always around, but in very smallnumbers seemed to come out of nowhere and cause TSS cause these symptoms and

particularly in women of child bearing age. It was mystery as to why this particular

group were susceptible to this terrible infection which had a fairly high mortality

rate from shock. It was a result of these women using Rely tampon, which was super

absorbent so it could remain in place for longer than a regular tampon, and now

they now that the material in these tampons actually stimulated the s. areas in the

vaginal tract to produce TSST-1. Not only that, blood was actually food for the

bacteria. So they grew well and produce more of this toxin as a result of this tampon

and this incidence of TSS went way down. It can still occur today not just in women

but also in men, once again it depend on the strain. Does it have the gene for the

production of that particular toxin? If you are infected with this particular strain youcould get TSS male or female and it can be life threatening infection. So today its not

as common but they are still a couple 100 cases every year in this country.

[19] [Staph Toexmias-3]

[Dr. Boylan]The third one staph food poisoning. A toxin is ingested. So I also

mentioned before these toxemias have a very short incubation period, a matter

often of hours, especially this one. Its a toxemia and incubation period might only be

3-5 hours because as opposed to an infection if you are infected with a bacteria or

virus you are not infected with a large enough number to cause the signs and

symptoms of the disease it takes a few days for the microbe to build up to critical

mass and all of a sudden you have the symptoms of the infection. If you have alreadyingested the preformed toxin that the bacteria produced its not going to be very

long before you start to feel sick. SO toxemia have a shorter incubation periods than

infections. With s. aureus the infection is ingested. The story I like to talk about is

that its summer and you go out to picnic. Sandwiches with mayo, deviled eggs and

ham. You leave your basket on the table its a hot day, and bacteria there like s.

areaus are incubating there in the food that you prepared. After a few hours you

come back to have lunch. Well you know maybe to be safe I could heat it up to make

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the food safer, but the problem with s. aureus that produces this toxin is very heat

resistant. So anyhow you have incubated the bacteria in your food, they are

producing the potent toxin in the food that you left on the table, you then eat that

food and take in that toxin and in a matter of 3-5 hours you are going to get very

sick. You don't have to have the bacteria grow in your body at all toxin does the

work. As you saw before toxin is a super antigen just like the other examples,release of cytokines. The toxin is very heat resistant it survives cooking your food.

SO even if you are bale to cook your food as you recall in the first or second lecture

about bacterial pathogenesis we talked about the differences of exotoxins and

endotoxins. Exotoxins like the one we are talking about here they are generally heat

sensitive. You heat them at 60 degrees for maybe 1/2 hour you can destroy the

exotoxin not an exotoxin. This particular exotoxin is very heat resistant, it is hardy

and very tough to destroy. It is a exotoxin, a super antigen, an another name is

enterotoxin because it works in the gut. So why are people so sick? The symptoms

are intense pain, vomiting and diarrhea. Projectile vomiting and diarrhea you got to

watch out for that too because your body is trying to get rid of this toxin, and any

orifice it can possibly use. This enterotoxin binds to cells in the gut that control thevomiting reflex signals to the brain. Get this stuff out vomit it out also diarrhea. So

the person feels very sick. There is cramping a lot of gasses produced as well and

you want to die you want someone to put you out of your misery its a painful

episode. The good thing is you always recover a day or so later when the toxin is

washed out of your system you will feel better in a couple days, mainly due to

cramping and gas produced. Treatment, you really cannot due to much, no abx

because its only a toxin bacteria may or may not be there but the toxin certainly is.

So bed rest maybe replenish fluid being lost, but just wait it out till the toxin is

diluted from the body.

[20] [Recent news][Dr. Boylan]Recent news, well flu in children going back to staph in general, s.

aureus we talked about primary and secondary infections sometimes one infection

will damage so much tissue that it will lead to an infection by another microbe. Well

we know now that these flu epidemics that due so much damage to our respiratory

tissue and children come down with secondary bacterial infection. So they were

harboring some staph which they were keeping under control whatever the normal

levels are of this bacteria, but with this damage done by the flue the s. aureus has

caused serious secondary infections leading to pneumonias and these children have

lung disease and need a ventilator to help them breath. Not only that but these staph

that cause secondary infection (flu is the primary infection) the staphs are MRSA:

methocyline resistant s. aureus. SO we know that MRSA are out there we will talkabout that next. These children have been infected by MRSA and it can be very

dangerous. Lets talk about MTSA

[21] [MRSA-1]

[Dr. Boylan]Methicillin is a abx and in works very similarly to penicillin it is a beta-

lactam, it inhibits cell wall synthesis, the peptidoglycan synthesis, but it is resistant

to penicillinase. So you have a patient that has a staph infection, you find out that the

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staph is resistant to penicillin you would switch to methicillin. Methicillin would

work and destroy the s. aureus. Even though the were resistant to penicillin they

were sensitive to methicillin ok great we found an ax that worked. Well guess what

happened? The bacteria found a way to become to both methicillin and penicillin.

The bacteria became resistant o penicillin because of the plasmid, and now the

found that they are resistant to methicillin. How are the resistant it methicillin? Dothey produce an enzyme like penicillinase? No its completely different way that

MRSA become resistant to methicillin. Now just a little bit of chemistry the cell wall

synthesis we talked about a few months ago. Remember when we had the cell wall

synthesis the peptidoglycan strands have to be interconnected a bridge has to be

formed between the separate strand of peptidoglycan so a rigid cell wall can be

formed. There is an enzyme that forms that bridge called transpeptidase. The

peptidoglycan has amino acid and a peptide bond forms. SO the enzyme is called

transpeptidase. Penicillin binds to transpeptidase thatshow it works and

transpeptidase cannot form the bridges between the strands and eventually the cell

gets so large that it burst it lyses. Ok so methicillin what happens when it becomes

resistant the bacteria find a way to form a different transpeptidase they alter thatenzyme just a little bit make it a different target for methicillin and now the continue

to form peptidoglycan. Point being its not an enzyme that make it resistant but a

changing of the target of the abx the enzyme changes a little so the methicillin can

no longer bind to it so the abx is not effective and the bacteria can grow. A

transpeptidase another name for it PBP, penicillin binding protein. It is the exact

same things as transpeptidase it binds the penicillin. Its normal fountain is to form

that bridge but it also binds to penicillin

[22] [MRSA-2]

[Dr. Boylan]A transpeptidase another name for it PBP, penicillin binding protein. It

is the exact same things as transpeptidase it binds the penicillin. Its normal fountainis to form that bridge but it also binds to penicillin. So how does s. aureus become

resistant to methicillin? It has a gene called the mech A gene in it chromosome not in

plasmid or phage gene. It is found in more and more s. aureus, and this mech A gene

allows for the production of the altered transpeptidase. So this transpeptidase is

PBP as a result of the mech gene coding for another transpeptidase that will not

bind methicillin and will survive. Unfortunately these MRSA strains you think ok we

will find something else we have tons of other abx, we may be lucky and find

something that does work, but for some reason these MRSA become resistant to a

lot of abx, not just cell wall abx but others too, others that act on cell membrane or

protein synthesis. On of these superbugs I guess you would say they really are

resistant to a variety of abx. They are not sure why but MRSA these strains areresistant to methicillin and others as well. Ok so thatsit for MRSA

[23] [S. epidermis]

[Dr. Boylan]Another staph that we are going to mentions is staphylococcus

epidermidis and guess where it resides? We all have this one it is part of normal

microbiota it is all over every skin cell is teeming with this particular bacterium.

Unlike S. aureus which some may carry but some may not. S. aureus found on skin

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but also on tip of the nose. Anyhow, staph epidermis is common skin commensal. It

colonizes in implanted devices especially prosthetic heart valves, and native valves,

artificial joints, and IV catheters. So imagine giving an iv catheter the do it all the

time s. epidermidis is always there right there at the site of injection, and what if you

don't disinfect or use and antiseptic on that area and some of the staph on that site

get into the skin and go to underlying tissue and even to the blood stream, and thathappens a lot. These formerly thought to be innocuous bacteria have an opportunity

to cause an infection inside the body. Inside the body they can colonize our tissues

under the skin, and grow in the bloodstream. They look for prosthetic devices they

look for heart valves or hip replacements and stick to them. So what is the main

virulence factor of these bacteria? it is the capsule. This is a large capsule and as you

know and you can quote me you can never underestimate the power of the capsule

because it plays such a major role in many infections. The capsule protects against

phagocytosis, it helps them survive longer outside of the body, it also helps them

grow and stick to prosthetic devices. Once they stick it helps them grow and form

more capsular material that lets them adhere more tenaciously thatswhen they

start to do there damage. Danger of course is that they can cause septicemia, theycan multiply in the blood. Hopefully, bacteremia when bacteria get into the blood we

hope that phagocytes an neutrophils come into play and come and destroy these

foreign invaders. Well if bacteria begin to grow in overwhelming numbers is called

septicemia and it causes orang failure an can lead to death. On test that can be done

is there is an abx called novobiocin, and this particular species of staph is sensitive

to novobiocin. I mention it now because the one will talk about next is resistant to

novobiocin so in the lab it is hard to tell what species you are working with so you

make up Petri dish with nice rich growth medium and you add novobiocin and see if

it will grow or not grow. If it does not grow it means the bacteria is sensitive to

novobiocin. SO this particular species is novobiocin sensitive. The next one we will

talk about is novobiocin resistant. So they do this a lot to differentiate between theseto species

[24] [S. Saprohyticus]

[Dr. Boylan]Saprohyticus causes urinary tract infections- cystitis, bladder

infections. It is the number 2 cause of UTI in women. E.coli is 1 in all age groups men

and women. Population at risk, mainly, well women are more prone to these

infection caused by this bacteria because its part of normal vaginal flora. The

infection caused by this bacteria is also know as, lovingly, as honeymoon cystitis

because they find it most commonly occurs in females on there honeymoon. Here

the bacteria are already there, and as a result of sexual activity they are stirred up I

guess you could say and they multiply. I think the main virulence factor well talkabout next is its ability to adhere it forms and adhesionn that really sticks to vaginal

tissue and even after urination it holds on and colonizes and multiplies and get to

the bladder to cause cystitis. The symptoms of all UTIs are similar, a burning

sensation upon urination, and urge to go more frequently. Treatment, you usually

let it run its course. Let me see if they have an abx. Yah there is one, sulfa drugs like

trimethoprine sulfa drugs in general, but thatsthe best. And once again you try to

grow on a medium with novobiocin it will grow so its novibiocin resistant.

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Begins streptococcus lecture[1] [The Streptococci]

[Dr. Boylan]Streptococci. Remember staph like S. Aureus, gram-positive cocci that

grow in grape like clusters.

[2] [Streptococci]

[Dr. Boylan]Strep grow in chains, like pearl necklaces. A string of cocci. Properties,

they grow in chains, non-motile, catalase negative. This is a very simple test to do in

the lab and itsa very powerful test b/c it will distinguish b/w the staph and strep.

Remember staph is catalase positive and strep is catalase negative, yea gram-

positive cocci should be in chains but sometimes microscopically you cant tell. They

dont always grow likethey do in the textbooks. Sometimes youre confused. Is thisstaph or strep. You get a sample of the bacteria. You put it on a glass slide, let it dry,

add a drop of hydrogen peroxide. If it begins to bubble up immediately it is catalase

positive. It produces an enzyme catalase that is breaking down hydrogen peroxide.

They are catalase positive. Strep are catalase negative. At least you will know which

of the two genera you are working w/ the test. Its a facultative anaerobe. It grows

anaerobically or aerobically.

[3] [Streptococci]

[Dr. Boylan]Here are the main culprits of the strep genus, S. Pyogenes. Youll see a

lot of these infections too. I want to go back to a point I made last time when a lot of

these bacteria are part of our normal microbiota of 20-30% of us. They are onlyfound in humans. They are not always causing infection or strep throat. They dont

always make themselves known but they have to continue exist somewhere in the

human population b/c they dont exist in animals. This is another one, S. Pyogenes.

Can cause infection of the throat, strep throat, skin, (some word) we saw before,

where the skin becomes very red and has a rash. It is also known as the flesh-eating

bacteria. Heres one genus and species, S. Pyogenes, different types/ strains of it like

there are different strains of human strains of the human race, but different strains

have different virulence factors able to cause one infection or the other. Strep throat,

skin infections, etc. We will mention briefly S. agalactiae, which indicates a bacteria

thats in the bloodstream of newborn, and now there is a vaccine/ treatment that

you give to expecting mothers during the time of delivery to prevent this type ofinfection. S. pneumoiae, that causes pneumonia. Dont limit yourself to thinking that

this bacteria is only the cause of pneumonia, it can cause Otis media (middle ear

infections) and most common reason in children, and also meningitis. E. Faaecalis,

also a strep. Use to be S. Faecalis. A few prosperities made it differentiate it from the

other group. So-called Viridians group that cause caries and endocarditis. What does

viridians mean? Green. I always thinking of (some name), Joe Green. Viridians, are

green. These are the bacteria that in our oral cavity. Bacteria that cause caries, other

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infections, other strep that are routinely that dont seem to do much damage. They

are all viridians streptococci. Which means when they grow on media w/ blood in it,

they will partially hemolyze the red blood cells and when they form colonies there is

a green zone around them. These bacteria grow, from colonies, partially hemolysis

the red blood cells, lead to the green/yellow appearance.

[1] [Classification]

[Dr. Boylan]How do you classify the strep? You have the brown classification and

hemolysis (we just mentioned that). There are three kinds of hemolysis that can be

shown by strep: alpha, beta, and gamma. All bacteria are one of these 3 but only the

strep use this system to identify these species. This brown classification. Hemolysis

of blood agar. All bacteria are one of the 3 w/ strep. Thats one of the properties we

use to identify them. Groups called Lancefield group. Well talk about that. Types of

strep called M protein. Getting back to the hemolysis. Alpha, beta, gamma. We just

talked about viridians hemolysis where those caries bacteria and they grow colonies

and partially hemolyze RBCs and form green. Thats called alpha hemolysis. Where

they partially lyse the red blood cells in the media they are growing on to form thatgreen color. Other bacteria like S. Pyogenes are beta hemolytic that means when

they are growing from colonies on a blood agar medium they will completely

hemolyze the blood cells, and lead to a clear zone. Not green or yellow. Its just clear.

You see it through. You see right through the plate. It completely destroys the RBCs.

The third is gamma hemolysis which mean those are strep that cannot hemolyze the

blood agar. They dont have the enzymes, they dont cause green/ clear hemolysis.

No hemolysis. The strep are gamma hemolytic.

[1] [The Streptococci]

[Dr. Boylan]Lets look at the groups. Well finish up talking about the group and

type. Lancefield classification. Rebecca Lancefield. Has everyone ever heard of herand her work in an immunology lab? She was a pioneer in immunology and worked

in Rockefeller University. She found a way and everybody heard of Rockefeller

University up the street on 1stavenue? Its the top places in the world for her

research. It was started in the 1900s by Rockefeller b/c one of this grandchildren

died from S. pneumonia. Even today its a very serious infection. Many people die

from it. He went on to set up an institution where they would do the most of the

effort towards solving infectious diseases. This was the time before antibiotics.

Thats how this started and Rebecca Lancefield was one of the people who started

director in the 20s. How do you classify strep in different ways. We can group them,

the various species of strep in different groups based on their cell wall composition.

Especially the C-carbohydrate. Its a carbohydrate found in the cell wall of strep. Itsantigenic. It will illicit an antibody response. She found over a period of time, that

most of them can be put into groups AU. A large number of groups based on this

C-carbohydrate cell wall component. She called S. Pyogenes the major pathogen of

this strep in addition to S. Pneumoniae as group A. Group A strep. That refers only to

S. Pyogenes. It has a C-carbohydrate. Every group has its own C-carb composite that

makes it a member of that particular group. In group A, this group A carb in S.

Pyogenes is composed of rhamnose and GluNAc. Every group, has their own unusual

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combination of sugars. In group A its that. Group A strep means S. Pyogenes. Its

called a group b/c of its sugar. Group B- S. agalactiae, Group D- endococcus. There

are also some species of strep that they are not able to put into groups. It doesnt

have an unique carb in their cell wall. One of them is S. Pnuemoiae. They are called

non-groupable. They dont have a recognizable C-carb. Even S. Mutans, the culprit of

caries, is a nongroupable strep. They have not identified a particular sugar in the cellwall.


[Dr. Boylan]S. Pyogenes, is group A. Its B-hemolytic. It has a capsule and its non-

antigenic. So thats happened w/ some bacteria that have a capsule. Most of the time

capsules are antigenic. Were going to see w/ the S. Penumoiae that the capsules are

very antigenic. The capsule, polysaccharide found are extremely antigenic. They

illicit an immune response. This particular one doesnt. What would it be a reason it

wouldnt cause an antibody response? Maybe our immune system does not

recognize this capsule as being foreign. Oh heres a strep thats covered w/ a capsule

that we think we shouldnt attack or destroy or interact w/. Thats mainlyhyaluronic acid. The point being, the composition of the capsule of these bacteria is

not an antigen b/c its not recognized by our immune system as being a foreign

material so it doesnt try to do what antibodies do, bind to the capsule and lead to

the death of the bacteria. Thats unusual. We talked about C-carbohydrate. Its

habitat is intact skin, mucous membranes, it can progress rapidly to cause serous

infections. Transmission aerosol and direct contact. Heres another one S. Pyogenes

only found in humans. Part of our normal microbiota but it can cause life

threatening infections when it has the opportunity or when it has the trigger to

emerge from this quiescence state on the skin/ mucous membrane of the throat and

turn on its virulence properties and do damage. Maybe same more infection, stress,

malnourishment can trigger this bacteria to do damage. Well continue w/ infectionsand strep throat tomorrow.


[Dr. Boylan]


[Dr. Boylan]


[Dr. Boylan]


[Dr. Boylan]

[1] [The Streptococci][Dr. Boylan]


[Dr. Boylan]

04: strep

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