1. Microbial Pathogenesis Flashcards
Microbial diseases are also called infectious diseases
These have been the number one cause of ____. In the beginning of 20th century the life span was 47 years in America and other countries were even lower. The majority of deaths were from infectious disease
Slide shows 10 leading causes of death
After 100 yrs the cause is different, first cause is ____ followed by cancer
human suffering
heart disease
This shows Infectious diseases, the death rate has gradually declined
Three things have caused this change
• One is improvement of ____ condition, for ex. we
learn to purify and clean the water by using ____
• Second is the discovery of ____
• Third is ____
The peak is the 1918 ____, it was very scary and hopefully won’t happen again
We have made dramatic improvement in controlling infectious disease, we expected the rate to come down to 0 but it it didn’t happen
human sanitary
chlorine
antibiotics
vaccine
spanish flu
Streptococcus
New diseases are called ____ disease
Picture shows scar left from flesh eating bacteria, this streptococcus pyogenes bacteria is not new it causes a lot of disease all the time e.g. ____, rheumatic fever
20 years ago people noticed very invasive new strain which causes massive destruction of tissue so it’s called ____ bacteria
This boy is lucky to survive because the death rate of the flesh eating infection is ____
emerging
scarlett fever
flesh eating
50%
Normal flora and Pathogenic Bacteria
Normal flora are those microorganisms that are frequently found on or within the body of healthy people.
Pathogenic bacteria are those that are normally not found in ____ individuals and once they enter hosts, regularly cause ____..
Does every bacteria cause disease? The answer is no
Everybody hosts thousands of species of bacteria and hundreds of viruses everyday
healthy
diseases
Some tissue hosts lots of bacteria, like skin, throat, intestines ,and genital system. These usually don’t cause disease.
In each adult you can find at least a trillion bacteria in their skin, 10 billion bacteria in their throat and even more in their intestine, like 100 trillion.
Some tissue should be sterile like the ____, ____, and ____ - any bacteria there has diagnostic significance
blood
brain
urinary tract
Normal flora are important for our health, not only harmless, they protect us from ____ bacteria and ____ disease.
Microbiota is associated with ____
Some therapy will change that microbiota and replace a skinny person’s flora and they will be normal
pathogenic
autoimmune
cancer
This recent Nature paper mentions if you disrupt microbiota by antibiotics it will screw up normal flora in intestine and will cause ____
If you disrupt normal flora bacteria it will lead to ____ cancer. Normal floral organisms are important to our health
adiposity
colon
TWO TYPES OF INFECTIONS
● Primary Infection
caused by ____ pathogens, the organisms normally not found in healthy human bodies. These microorganisms regularly cause diseases when they enter a host. This type of infection is termed primary or exogenous infection.
● Opportunistic Infection
caused by so-called ____ flora microorganisms, the organisms that rarely cause clinical problems under normal conditions and in healthy people but cause diseases in certain circumstances and in ____ individuals. The infection caused by opportunistic pathogen is called ____ infection.
We mentioned ____ which is a perfect example of exogenous pathogen (primary infection).
If you cut your skin and normal flora bacteria gets in your ____ skin where it shouldn’t be, it is called an opportunistic infection
exogenous normal immune-compromised salmonella deep
There are thousands of species of bacteria around us, majority are normal flora but some of them are pathogenic. They have been classified based on ____ and ____ difference which is important for clinician to identify bacteria in association with disease
____ methods have been made to see them
morphological
physiological
staining
The gram staining is very common and easy, you have a smear and have bacteria on a slide, add a die which is called ____. Bacteria absorb the die and make themselves ____, then wash and treat with ____ which can form a complex with the crystal violet in the cell wall
You cannot tell the difference of gram positive and gram negative, so you treat bacteria with alcohol or ____ and the gram positive and negative can be distinguished in this step
For the gram positive, the ____ stays and the gram neg can be ____, so you have to counterstain with red die such as ____,
____ = gram positive, ____ = gram negative
You have to counter stain them with ____
crystal violet purple iodine acetone color decolorized texas red purple pink red die
Gram positive cocci (____)
Gram negative rods (____)
streptococcus pyogenes
e. coli
Major Groups of Microorganisms
- Gram positive cocci
- Gram positive rods
- Gram negative cocci
- Gram negative rods
In nature these are evenly present, but most pathogenic bacteria are ____ and ____ with some exceptions
gram positive cocci
gram negative rods
Typical Bacteria
Gram-positive Cocci – ____, Streptococci.
Gram-negative Cocci – ____, Meningococcus.
Gram-positive Rods – ____.
Gram-negative Rods – ____ and other ____ bacteria.
Not So Typical Bacteria
Acid-fast Bacteria – ____, Mycobacterium leprae.
Spirochetes – ____, Treponema pallidum.
Gram negative cocci are mostly ____, but you do have gonococcus that causes gonorrea and meningococcus
Meningococcus, 10-20 percent of healthy people carry it in their ____
Among college students, there is meningococcus all around and its from ____. For the people who do not carry it in their throat, it is pathogenic. Rants about frat parties at Penn (a girl died at HUP in one day from Meningococcus infection). Some colleges require the vaccine.
____ are most abundant in nature. Most of them are harmless, very few cause disease but one of them is Corynebacyterium diphtheria which was an issue but successful ____ programs reduced them
Gram negative rods have lots of pathogenic bacteria
I will introduce another staining technology, acid fast staining, for tuberculosis
staphylococci gonococcus corynebacyterium dpihtheria e. coli enteric
mycobacterium tuberculosis
borrelia burgdorferi
non-pathogenic
throats
partying
gram positive rods
vaccination
Tuberculosis has a ____ envelope and no ____ so they are resistant to gram staining, and require a special procedure that is ____ staining
Treat the bacteria with die in the presence of ____ and sometimes heat it up to facilitate the process
Then, the unique thing is once they are stained (tuberculosis) they are resistant to ____ by the acid; so treat the smear with ____ acid which removes the die from most bacteria, but in the tuberculosis bacteria, the ____ color stays.
waxy cell wall acid fast detergent decolorization 3% hydrochloric red
Then counterstain with the ____ and then you can see the red box in the blue background
blue die
Before the antibiotic era ____ and ____ were the two bacteria that caused the most deaths in all ages, but now antibiotics can control them well. These reemerged in the 80s causing new disease such as staph-____ and strep-____ bacteria
staph aureus
strep pyogenes
toxic shock syndrome
flesh eating
Gram stain of streptococus pyogenes
You see they are ____, gram positive and you see they grow in ____
purple
strings
Gram stain of Staphylococcus aureus
Also gram positive but they don’t form the chain, instead they ____like grapes
staphylo originally came from greek for “____”
cluster
bunch of grapes
H2O2 > catalase > H2O + O2
They are both gram positive, under the microscope you can tell the difference Staph and Strep can be distinguished by chemical reaction, the catalyst is the enzyme that can convert peroxide to water and O2.
Only staphylococci carry the enzyme and they are ____
Place a drop of hydrogen peroxide and if it is staph the reaction takes place and you will see a ____, if not, it is strep
catalase positive
bubble
Human Staph Species
HUGE LIST!
Staph is a big genus with many species. The most common species is ____ present on everyone’s skin and less pathogenic
Staph aureus is less common but more ____, it causes the majority of staph related diseases
The rest of them are relatively ____ besides staph aureus
Another way to differentiate the bacteria is by enzyme. Only Staph aureus carries the ____ enzyme
staph epidermis
pathogenic
avirulent
coagulase
Colonies of Staphylococcus aureus on an agar plate
staph aureus - the colony is very ____, and the ____ color is from the pigment they produce. Aureus is greek or latin for golden
The rest of staph is ____ and ____, so you can tell the difference between pathogenic staph aureus or avirulent bacteria
big
yellow golden
small
white
Coagulase test: a common test used to distinguish S. aureus from other Staphylococcus species.
The enzyme can induce ____ of serum
The test is easy, in slides you prepare the bacteria cell suspension and place a drop of serum and the enzyme can induce clotting activity if it is staph aeurus, so all the cells ____
The rest of bacteria, if coagulase nega?ve, they remain in suspension, so you can tell the difference
clotting activity
aggregate
Staphylococcal Diseases ● \_\_\_\_ (boils, furuncles) ● Staph Scalded Skin Syndrome (SSSS) ● \_\_\_\_ ● Staph Food Poisoning
• Some diseases are caused by ____ invasion and destruction of
tissue
• Other diseases are caused by ____ the bacteria can release
• Abscess is ____ invasion and destruction of tissues, most of the time it happens at the skin from cuts or ____ and provides opportunity for the bacteria to get into tissue, that’s why in the skin we get ____ (medical term ____)
Staph Scalded Skin Syndrome is old, first report in 1878 in London, 300 infants less than 1 month old developed scarred skin disease. It started from ____ skin infection
abscess toxic shock syndrome (TSS) direct toxin direct burns boils furuncles
minor
An Abscess Case
Mr. S., a pastry chef, cut his left forearm with a knife while working. Over the next week, he noticed swelling, redness and warmth at the site. After four more days, he developed fever of 39OC and came to an emergency room with severe low back pain. Physical examine revealed a swollen left arm with an area of central softness, indicating an abscess. The lab report showed that he had a high white blood count. S. aureus was cultured from the pus aspirated from his arm.
The S. aureus was resistant to ____, but sensitive to ____, which was used to treat Mr. S with good result.
He was treated with oxacillin and recovered, but had a big scar on
his arm. The process is complicated, he got a cut and infection which first induces ____ inflammation and chemotaxis, the white blood cells fight intruding bacteria but some bacteria can get in the neutrophils and kill them, this causes the release of lots of ____ which damage tissue and cause puss
penicillin
oxacillin
acute
lysosomes
Staphylococcal Scalded Skin Syndrome
● Occur mainly in ____ and children.
● Abrupt onset of ____.
● Large bullae or blisters form and are followed by ____ of epithelium.
● Caused by the production of a toxin, known as ____.
Starts with localized erythema but it spreads and the whole body is red followed by blister because bacteria can release toxin in the blood stream to the whole body
infants
erythema
desquamation
exfoliatin
Staph Scalded Skin Disease
You can see blisters and bulla over the body because the toxin can destroy the ____ connection to separate the top layer of skin with dermal layer and create liquid fluid between that looks like a big blister.
Those blisters can be popped and the skin peels off all because of the toxin
Good part is the mortality is ____ so no baby dies and in ____ days the skin peels off and there will be soft skin again
intercellular
low
7-10
Clinical Manifestations of Toxic Shock Syndrome
● High ____, sore throat and ____.
● ____-like rash, followed by skin
desquamation.
● ____.
● Abnormalities in multiple organ system (____, diarrhea, ____ and hepatic damage).
● Severe ____.
● 95% of these cases occurred in ____ aged 20-40. Onset of illness often occurred during ____.
CDC immediately issued research to determine risk factors for this disease and set up nationwide surveillance to estimate magnitude of disease
After only one month and three results pointed to the linkage between the use of ____ (Rely brand) and TSS. This explains why it happened to women especially during their period
fever muscle pain sunburn hypotension vomiting shock women menstruation
tampons
The disease dropped to very low when Procter and Gamble pulled the ____ from the market. That proves tampon was responsible.
tampon
Research found that ____ can grow in the tampon
and release toxin. Vaginal microflora is dominated by other bacteria but using the tampon changed the niche and ____ could not grow so Staph aureus takes the opportunity to grow and release toxin ____ can go in ____ and cause systemic symptoms
How does toxin work to cause the disease? Toxin functions as a ____
staph aureus lactobacilli TSST-1 blood stream super antigen
Normal antigen has to be processed by antigen presenting cell that will present MHC class \_\_\_\_ complex to stimulate CD4 T cell and only a particular T cell with a particular T cell receptor can recognize the antigen presented by MHC Class II. I.e. If you have bacteria A you get a specific T cell for \_\_\_\_
Super antigen by name means not that specific. What they do is, you don’t need any antigen in the middle, the super antigen can at one end interact with ____ on the outside of groove, and at the other end interact with any ____ receptor to make the bridge. This bridge is ____. The bridge is sufficient to activate the T cell. Lots of them can be activated and produce cytokines like ____, IL2, and ____ and those diseases cause ____. Super antigen can deplete all the ____ and this is a strategy bacteria use to destroy the immune system
II
bacteria A
MHC Class II T cell non-specific IL1 TNFalpha shock T cells
The last toxin associated disease is ____, caused by Staph and staph can produce enteric toxic that can cause ____.
food poisoning
diarrhea
Case - continued
The day after Mr. S was admitted to the hospital, the local public health department was notified that eight restaurant customers had developed severe vomiting and diarrhea after eating there. Six of the eight people had eaten cream pie. Cultures of remaining cream pies in the restaurant refrigerator were positive for ____. ____ was detected in the pies.
The most common food that gets contaminated is ____, ____ and ____.
staph aureus, it is not infection it is the ____ that is causing the disease. If you heat up food you may kill all the bacteria but not inactivate the ____
s. aureus enterotoxin A processed meat tomato salad cream dish
toxin
toxin
Treatment of Staphylococcal Diseases
● Penicillinase-resistant Penicillin derivatives,
such as ____, ____.
● ____.
● Combination therapy using ____ drugs and minocycline or ____.
Staph aureus is very easy to develop ____. Penicillin was developed in the 1940s and the next year people already found staph strain that are resistant to penicillin so there is a high tendency to develop resistance
Today there are synthetic compounds derived from penicillin like nafcillin and oxacillin, some of them from community acquired staph infections, such as that of the chef, still work. But for hospital acquired infections the majority of them are resistant to all those derivatives as well so don’t bother to try. Those bacteria we call them ____
nafcillin oxacillin vancomycin sulfa rifampin
drug resistance
MRSA
Treatment of Staph Diseases
So far only one antibiotic is still working, ____, that bacteria are still sensitive to. This is the last drug to treat a very serious staph infection. But, in recent years you heard of news of some strain of Staph aureus with reduced susceptibility to the vancomycin already discovered in japan and later new jersey and Michigan. That suggests theres a possibility of Staph aureus with full resistance to vancomycin maybe already exists so if they jump to humans we will be in big trouble.
vancomycin
Classification of Common Streptococcal Pathogens
S. pyogenes
Serological classification: ____
S. agalactiae
Serological classification: ____
S. aginosus, S. equisimilis
Serological classification: ____
S. bovis
Serological classification: ____
S. anginosus
Serological classification: ____
S. pneumoniae (???)
S. mutans, S. salivarius, S. tanguis, S. mitis, S. milleri
Serological classification: ____
LOOK UP THE HEMOLYTICS MY BOY!
A B C D F G viridans strep
When you grow bacteria in the blood agar -commonly used in microbiology lab-, lots of pathogenic bacteria will only grow in the ____.
The next morning you will see some of the colony are surrounded by a zone of complete hemolysis so the blood cell is lysed by something ____ by bacteria.
This type of Strep we called ____ hemolysis. There are many other types of Strep with no zone surrounding that we call ____ hemolysis, also there is something between that can create the zone but no complete hemolysis only partial lysis of blood cell. The zone is not clear but ____ and those we call ____ hemolysis.
Majority of the pathogenic bacteria belong to the ____ hemolysis
blood agar released beta gamma greenish alpha
beta
Another group of Strep is called Viridans Strep that are ignored in the ____ classification but are important in dentistry.
They belong to the hemolytic ____ or ____ so they are not that virulent.
Important to dentistry because they comprise species inhabiting the ____. In our normal oral microflora they account for 30 to 60 percent of them. Some species like Strep mutans are directly associated with a lot of problems because they can form ____ leading to caries.
lancefield alpha gamma oral cavity plaque
Streptococcal Diseases ● \_\_\_\_ (Strep throat) ● Scarlet Fever ● \_\_\_\_ ● Skin infections (impetigo, \_\_\_\_) ● \_\_\_\_ (flesh eating diseases) ● Delayed Sequelae -- \_\_\_\_, glomerulonephritis
Pharyngitis happens especially to ____ age 5-10. In winter, kids claim they have a sore throats but 70 percent of the time it is the common cold by ____ but 30 percent it can be strep throat.
pharyngitis streptococcal toxic shock syndrome erysipelas necrotizing fasciitis rheumatic fever
kids
viruses
Pharyngitis
This starts from the ____ throat with headache, fever. Looks like not a big deal to kids because that happens often but it is important to distinguish strep throat vs common cold. They need ____ for strep throat and any delay of the treatment may have consequences like ____ or rheumatic heart disease.
inflamed
antibiotics
rheumatic fever
Scarlett fever looks like not a serious disease now but 100 years ago it was a big killer for kids. Even before antibiotics were discovered, scarlett disease became a milder disease. It happens few days after strep throat, number one if the kid is not ____, number two if the bacteria caries a particular ____ that caries toxin that causes scarlett fever.
If you’re lucky a bacteria without the bacteriophage will not cause the disease.
Spread of ____ on the body tells you it is the toxin, it starts with ____ and spreads to extremities like face hands.
treated
toxin
rash
upper chest
Scarlet fever
Color of tongue changes from white to ____ and call it ____ tongue. It used to be a deadly disease but now it is milder and we have ____, not a problem at all.
red
strawberry
antibiotics
It starts with a skin infection and becomes a ____ infection. So the mortality rate is much higher, given the name toxic shock-like syndrome (TSLS) by ____.
The reason the mortality is 10x higher than TSS is because the bacteria can get into the bloodstream and become ____.
The mechanism is very similar to TSS the bacteria cause toxin that functions as a ____ in the blood stream. The two toxins have different ____ sequences but they cause very similar ____.
bloodstream
strep pyogenes
bacteremia
super antigen
amino acids
symptoms
This slide shows you anatomy of the skin, different layers, epidermis, dermis, superficial fascia, and subcutaneous tissue. Depending on the different ____ and side of ____ you get a different type of skin infection.
layer
skin
Impetigo
Infection in the ____, you get Impetigo. It is not very deep and usually the infection is ____ with crusting legion.
epidermis
localized
Group A Streptococcal
Erysipelas
If the infection is deeper, to the ____ layer it becomes ____. Characterized by spreading erythema edema in the ____ and ____.
dermal
erysipelas
feet
face
The infection can be even deeper, and deeper to the superficial ____, and that infection is called ____
fascia
cellulitis
Group A streptococcal cellulitis
Similar to Erysipilas but the differences is cellulitis is ____ because the infection is deep and erythema and edema is spread. This girl got the infection after ____ for small pox (breaking the ____ during vaccination).
painful
vaccination
skin
If the infection can go even deeper, the ____ tissue, can become ____, flesh eating bacteria
subcutaneous
necrotizing fasciitis
Necrotizing Fasciitis
Starts with trivial skin infection but progresses very ____ and skin color changes from purple to ____. Then the skin dies and muscle and ____ is exposed.
fast
blue and black
fat
Necrotizing fasciitis
Flesh eating bacteria is not a ____ term, the media gave it that name
It is very fast process, it happens in one ____
People get a cut with a little bump and very quickly it spreads and by the time they realize it is too late and mortality rate is at least ____ percent. Since the disease is aggressive the treatment is aggressive and ____ are too slow, it requires ____ procedure. Surgical debridement or ____.
scientific/medical day 50 antibiotics surgery amputation
Delayed Sequelae of Streptococcus Infection – Rheumatic Fever and Nephritis
After all the symptoms are gone, the kids have a new problem including ____ and ____ and chorea which suggests the disease affects the ____ and central nervous system.
Rheumatic Fever is only associated with ____ strep throat not other types of infection like impetigo skin infection, but the skin infection can lead to different types of delayed sequelae such as ____ which is auto disease against the kidney.
arthritis
carditis
heart
pharyngitis
nephritis
Rheumatic Fever
● Rheumatic fever is a ____ of strep pharyngitis.
● Certain people have a ____ predisposition.
● In rheumatic fever, damage to heart, kidney is not the result of bacterial infection, but ____.
● Rheumatic fever can be completely prevented by treating strep pharyngitis with ____.
Bacteria can cross react with myocyte in heart so immune system keeps attacking your heart, so this is a bad disease and once you get it, it will stay with you for ____.
Every time you get a strep infection it will trigger the reactivation. It is impossible not to get recurrent infection because ____ is everywhere.
The Rheumatic is not treatable by penicillin because by that point it is the ____ triggered by the bacteria originally
delayed sequela
genetic
autoimmunity
penicillin
life
strep pyogenes
immune sytem
Group A Streptococcus virulence factors ● M protein -- Anti-phagocytic, degrades \_\_\_\_. ● M-like proteins -- Binds \_\_\_\_ and \_\_\_\_. ● F protein -- \_\_\_\_. ● Pyrogenic exotoxin A -- \_\_\_\_. ● Streptolysin -- lyses \_\_\_\_. ● Hyaluronidase -- \_\_\_\_
So many diseases associated with one single species of bacteria. Because the different strain carry different virulence factor this contributes to different disease. For example TSLS, that’s because Strep pyogenes produces ____.
Flesh eating bacteria produces enzyme ____ and this destroys connective tissue and lets bacteria spread fast, they will not spread fast without producing this enzyme.
____ is most important virulent factor because any strain that carries M protein caused disease and ones that did not were ____
C3b IgM IgG adhesin TSLS leukocytes spreading factor
exotoxin A
hyaluronidase
M protein
avirulent
M protein of streptococcus pyogenes
____ protein, fibrillar molecular on the surface of the bacteria ____ group sticks in cell membrane and amino terminal exposed to the outside. Each fibril have two ____ helix molecules around each other on the surface.
People believed the M protein helps bacteria associate with target and tissue but people found it was wrong and the real function is the M protein can protect the bacteria from ____ when bacteria are in bloodstream where macrophages and neutrophils try to destroy them. Function is M protein can recruit serum factor called ____ and complement molecule of innate immunity can send a signal to macrophage/neutrophils. H factor can destroy ____ to make the bacteria invisible to the macrophages/neutrophils. So with ____ factor bacteria can survive and cause disease.
surface carboxy alpha phagocytosis factor H complements H factor
TREATMENT OF STREPTOCOCCAL DISEASES ● \_\_\_\_ ● Erythromycin and \_\_\_\_ in penicillin allergy. ● Vaccine against \_\_\_\_.
Strep is different from Staph. Majority of Strep is still very sensitive to ____ so most kids are given this, it is cheap and effective. Only for kids allergic we use other antibiotics like ____ and cephalosporins.
penicillin cephalosporins s. pneumoniae penicillin erythromycin
