D1 - Micp Exam #3

Front 1

Characteristics of Streptococcus

Back 1

- Gram positive
- Arranged in pairs or chains
- Non-motile
- Non-spore forming
- Most are facultative anaerobes
- Many are part of the normal flora
- Complex nutritional requirements
- Catalase negative (Differentiates them from Staphylococcus)

Front 2

Strep Group A and B are both __ hemolytic

Back 2

Beta

Front 3

Strep. pneumoniae is __ hemolytic

Back 3

Alpha

Front 4

Alpha hemolytic

Back 4

Have a green hue around the colonies. Essentially partial hemolysis. RBCs leak.

Front 5

Beta hemolytic

Back 5

RBCs completely lysed

Front 6

Gamma hemolytic

Back 6

RBCs not lysed at all.

Front 7

Group A Strep is normally found where?

Back 7

on skin and mucous membranes

Front 8

Diseases caused by Group A Strep:

*(Consists of a single species: Strep. pyogenes)

Back 8

- Pharyngitis: Strep throat

- Skin Infections: Pyoderma, Cellulitis

- Necrotizing fascitis

- Toxic shock syndrome

Front 9

Scarlet Fever

Back 9

the erythrogenic toxin of GAS causes generalized erythematous rash beginning on face and spreading to the rest of the body

Front 10

Acute glomerulonephritis

Back 10

Ab against Protein M form Ab complexes that deposit in glomeruli

Front 11

Major Complications of Strep. throat

Back 11

- Otitis media and sinusitis

- Scarlet Fever

- Rheumatic Fever

- Acute glomerulonephritis

Front 12

GAS is primarily a disease of children between the ages of...

Back 12

5 and 15 years

Front 13

Virulence factors of GAS

Back 13

- Adherence Factors:
Protein F binds fibronectin.
Lipoteichoic acid (LTA) – mediates attachment to epithelial cells

- Immunoavoidance Factors:
M protein, an antiphagocytic factor that binds Factor H = degradation of C3b = prevents opsonization by C3b and formation of C3bBb convertase (contains epitopes in common with some human tissue).
C5a peptidase - Prevents chemotaxis of phagocytes.
M-like Proteins - Bind to Fc portion of IgG AND IgG and Coats cell in host proteins.
Hyaluronic Acid Capsule - helps prevents phagocytosis

- Toxins:
Streptolysins - hemolytic and leukotoxic. O is antigenic, S is not.
SpeA, B, and C Exotoxins - superantigens, Able to activate large number of Tcells, Interacts directly with MHC class II. pyrogenic, mitogenic for lymphocytes, enhances susceptibility to endotoxins, produce rash.
Erythrogenic toxin - phage-mediated (lysogenic conversion). responsible for scarlet fever.
Streptodornase (DNase) - breaks DNA reducing the viscosity of the pus.
Hyaluronidase - spreading factor.
Streptokinase - lyse blood clots, responsible for rapid spread of GAS.

Front 14

Treatment of GAS

Back 14

- Highly susceptible to Penicillin G
- Aminoglycosides–ineffective
- Adequate treatment of S. pharyngitis within 10 days of onset will prevent rheumatic fever

Front 15

Virdans Streptococci

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- Large group of heterogeneous a hemolytic and g or non hemolytic streptococci

- S. pneumoniae – part of the S. mitis subgroup is the most virulent member

- Groups include:
Mitis.
Mutans.
Salivarius.
Anginosus
Bovis

Front 16

Local distribution of oral Streptococci

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- S. mitis: Buccal mucosal membrane

- S. salivarius: Tongue, salivary secretion

- S. sanguis, S. mutans, S. sobrinus: Dental plaque

Front 17

Streptococcus pneumoniae

Back 17

- Encapsulated Gram positive coccus

- Arranged in pairs or short chains

- a hemolytic if grown aerobically

- Colonies undergo autolysis (Central portion of the colony dissolves causing a dimpled appearance)

- Common inhabitant of the throat and nasopharynx

- Disease occurs when organisms spread: Pneumonia, Sinusitis, Otitis media, Meningitis

Front 18

Strep. pneumoniae Virulence Factors

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- Capsule: antiphagocytic. without capsule it loses pathogenicity

- Pneumolysin: alveolar necrosis and hemolysin.
slows cilia, reduces clearance

- Secreted IgA protease

- Neuraminidase: decreases mucus viscosity. exposes receptors

Front 19

Treatment of Pneumococcal

Back 19

- fluoroquinolones or vancomycin

- Vaccination of high-risk patients

Front 20

Group B Streptococci:

(Streptococcus agalactiae is only species)

Back 20

- Colonize the lower gastrointestinal tract and the genitourinary tract

- Primarily known as a pathogen of neonates: Causes septicemia, pneumonia and meningitis in newborns

- Most important virulence factor is the polysaccharide capsule

Front 21

Properties of S. aureus

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- G+ cocci with low G+C content

- grows in clusters, pairs, short chains

- yellow CFU on blood agar, β hemolytic. aureus = golden

- heat resistant

- non-spore forming, non-motile

- Catalase and coagulase +

- facultative anaerobe

- normal resident of nares

- produces numerous types of virulence factors and antibiotic resistant strains have emerged

Front 22

Virulence Factors of S. aureus

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- Adherence:
Polysaccharide A (ribitol teichoic acid) - binds to fibronectin.

MSCRAMMS - Recognize host proteins - collagen, elastin, osteopontin, etc

Coagulase - converts fibrinogen to fibrin leading to clumping of bacteria


- Toxins:
5 major cytotoxins (alpha, beta, delta, gamam and leukocidin) that lyse RBCs, PMN, macrophages and platelets, and are necrotic. Gamma targets lymphoblastic cells. Leukocidin only targets PMNs.

Exfoliative toxin - splits desmosomes in stratum granolosum epidermis. Responsible for staph scalded skin syndrome (SSSS) and bullous impetigo.

Enterotoxins - heat-stable proteins. A and D are responsible for food poisoning.inhibit water absorption from intestinal lumen, leading to watery diarrhea. B damages intestinal epithelia and produces colitis
B also implicated in some cases of TSS.

Toxic Shock Syndrome Toxin - superantigen. Able to activate 20%r of Tcells at one time. Interacts directly with MHC Class II. pyrogenic, mitogenic for lymphocytes, enhances susceptibility to endotoxins, produce rash


- Immunoavoidance:
Leukocidin and gamma hemolysin

Capsule

Protein A - binds to Fc portion of IgG. can interfere with phagocytosis

- Extracellular Enzymes:
coagulase - converts fibrinogen into fibrin (plasma clots)

lipase - splits fats and oils on skin, helps bacteria invade cutaneous and subcutaneous tissue

hyaluronidase - helps bacteria spread through tissues

staphylokinase (fibrinolysin) - dissolves fibrin clots

Front 23

Treatment of S. aureus Infections

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- Adequate drainage of abscess

- Initiate broad spectrum antibiotic

- Change antibiotic dependent upon antibiotic sensitivity (e.g. vancomycin for methicillin resistant strains).

Front 24

S. aureus Diseases

Back 24

Skin infections
Impetigo
SSSS
Nectrotizing fasciitis
Osteomyelitis
Endocarditis
Keratitis
Indwelling medical device infection
Toxic shock syndrome
Food poisoning
Pneumonia
Septicemia
Pyopneumothorax
Empyema

Kills 40,000 people/yr. in USA

Front 25

Staphylococcus epidermidis

Back 25

- Normal flora of skin, nose, and throat.
- Non-hemolytic, coagulase-negative, gram-positive cocci
- Can produce polysaccharide slime – facilitates adherence to catheters and prosthetic devices
- Causes opportunistic nosocomial infections
- Produces disseminated disease with multiple abscesses.
- Vancomycin is drug of choice.

Front 26

Staphylococcus saprophyticus

Back 26

- Occasionally found on skin or gastrointestinal and genitourinary tracts.
- Non-hemolytic, coagulase-negative; novobiocin resistant (unlike other staphylococci)
- Very common cause of urinary tract infection in adolescent females.
- Norfloxacin effective treatment.

Front 27

Enterobacteriaceae - Microbial Physiology and Structure

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- Gram negative rods
- All are motile (with peritrichous flagella) except Shigella, Klebsiella, and Yersinia)
- All are facultative anaerobes
- Simple nutritional requirements

Front 28

Distinguishing Characteristics of Enterobacteriaceae

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- Oxidase negative
- Lactose fermentation
(Separate Escherichia, Klebsiella, Enterobacter from other lactose negative Enterobacteriaceae)
- Resistance to bile salts (Separate Shigella and Salmonella from normal flora in this group)
-

Front 29

Types of enteric infections

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- Gastrointestinal infections
- Dysentery
- Skin and wound infections
- Enteric fever
- Septicemia
- Meningitis
- UTIs

Front 30

The Coliforms

Back 30

Escherichia sp. (E. coli)

Klebsiella sp. (K. pneumoniae)

Enterobacter sp. (E. aerogenes)

Serratia sp. (S. marcescens)

Citrobacter sp.

Front 31

Pathogenesis of Escherichia

Back 31

- Neonatal meningitis

- Urinary tract infections: Originate from gastrointestinal tract

- Diarrheagenic E. coli: Category B Pathogen. Causes ~300,000 deaths each year.

- Gastroenteritis:

Enterotoxigenic (ETEC): Mediated by heat-labile and heat-stable exotoxins, activates guanylate cyclase and stimulates secretion of fluid.

Enterohemorrhagic (EHEC): Produces cytotoxin (verotoxin) called shiga-like toxin.
Severe abdominal pain, bloody diarrhea, little or no fever.
< 100 viable bacteria can cause disease. Can lead to acute renal failure (Hemolytic Uremic Syndrome). HEC does not produce fever, which is fairly unique. Antibiotics make the bacteria produce more toxins, so they should never be administered to EHEC infections. uses type 3 secretion system to secrete proteins directly into epithelial cells. Cause rearrangement of actin in the cell to create pedestal. Cell can't regulate water as a result.

Enteropathogenic (EPEC; childhood diarrhea): Organism adheres to enterocyte plasma membrane and causes destruction of microvilli producing watery diarrhea. Infants< 1 year affected

Enteroaggregative (EaggEC; watery diarrhea): Infants < 6 months and AIDS patients

Enteroinvasive (EIEC): Invade and destroy colonic epithelium. Fever and cramps with blood and leukocytes in stool
Uncommon; often food-borne

Front 32

Properties of Shigella

Back 32

- aerobic
- non-motile
- gram-negative rods
- Small inoculum (~10 bacteria)
- Spread by fecal-oral contact
- Invade colonic epithelium
- Diarrheal disease is 2nd leading cause of mortality in <5yo population in the world (600,000 deaths/year)
- Most common cause of dysentery and persistent diarrhea
- Produce enterotoxins (e.g. Serine Protease Autotransporters)
- Clinical syndromes (1-3 days after ingestion): Cramps, Diarrhea, FEVER, bloody stools.
- Pathogenesis: Colonize small intestine and multiply during first 12 hours. Invasion of colonic epithelium results in lower abdominal cramps, difficulty defecating, abundant pus and blood in stool

Front 33

Important species of Shigella

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- Shigella sonnei (industrial countries)
- Shigella flexneri (underdeveloped countries, no Shiga toxin)
- Shigella boydii (Rare, mostly industrialized)
- Shigella dysentaeriae (Most severe, episodic outbreaks in developing world every 10 years or so)

Front 34

Shiga toxin

Back 34

Produced by S. dysenterieae

Irreversibly inactivates mammalian 60S ribosomal SU; stops protein synthesis

Targets sodium absorptive villus cell; produces decrease in Na+ absorption; more fluid accumulates in lumen

Toxin affects mucosal epithelial cells yielding bloody diarrhea

Front 35

Salmonella

Back 35

- Gram negative rod
- Motile
- Pathogenesis: Ingestion of contaminated water, food or by fecal-oral contact in children.

Enteric Fever (S. typhi, typhoid; S. paratyphi, paratyphoid): 10-14 day incubation period. Gradually increasing fever. Headache, muscle aches, malaise, and decreased appetite; gastrointestinal symptoms occur. Carriers (“Typhoid Mary”)

Gastroenteritis (most common): Symptoms 6-48 hours after ingestion. Nausea, vomiting, non-bloody diarrhea, fever, cramps, headache. Symptoms persist for 2 days to a week before abating. Infect patients with decreased stomach acid. Large inoculum needed (usually >100,000 viable bacteria).

Septicemia: In 10% of cases can lead to osteomyelitis, endocarditis or arthritis.

Front 36

Diseases caused by Proteus mirabilis

Back 36

Causes catheter associated urinary tract infections and recurrent kidney stones.

Front 37

Pathogenesis of Yersinia pestis

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- Bubonic plague (incubation period-7 days after bite from infected flea): High fever and inflammation of lymph nodes in groin or armpit. Without treatment, 75% die of bacteremia. 200 million killed in pandemic of 1300’s

- Pneumonic plague (incubation 2-3 days): Fever and malaise. Develop pulmonary symptoms within 1 day. Untreated >90% die

Front 38

Pathogenesis of Yersinia enterocolitica

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- Associated with contaminated meat or milk during winter months

- Gastroenteritis: Diarrhea, fever, abdominal pain lasting for 1-2 weeks. Chronic form can persist years. Can mimic appendicitis. May lead to septicemia, arthritis, intrabdominal abscess, hepatitis, and osteomyelitis

Front 39

Vibrio cholerae

Back 39

- Gram negative curved rod
- Facultative anaerobe
- Transmission via infected water and shellfish
- ID is HIGH (10^8)
- Cholera toxin responsible for symptoms: 2-3 days post exposure, diarrhea and vomiting. Massive fluid loss (up to 14 L/day) = rice water stool
Dehydration, metabolic acidosis (bicarbonate loss), hypovolemic shock (K loss), cardiac arrhythmia, renal failure

Front 40

Campylobacter

Back 40

- C. jejuni & C. coli
- Gram negative spiral rod
- Motile
- Thermophile
- Survives > 1 hour on hands & moist surfaces
- Survives refrigeration
- Sources: raw meat, raw milk, feces from animals contaminate water.
- Pathogenesis: incubation – 2 to 5 days. Febrile. Watery/bloody diarrhea, abdominal pain and nausea.

Front 41

Helicobacter pylori

Back 41

- Gram negative spiral rod
- Pathogen responsible for >90% of gastric and esophageal ulcers
- Detected via urease test and treated with acid stable antibiotic TMP-SXT

Front 42

Diseases caused by Pasteurellaceae

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- Meningitis: 2 months and three years of age. Long term sequelae such as deafness, speech impairment, and behavior abnormalities may occur following infection.

- Epiglottitis: occurs in 2-4 year olds with mostly boys being affected.

- Pneumonia: frequently associated with otitis media, meningitis, and septicemia

Front 43

General Characteristics of Mycobacterium

Back 43

- Gram positive rods
- Acid fast
- Lipid-rich cell walls
- Slow growing
- Species: M. leprae, Mycobacterium tuberculosis complex, non-tuberculosis species (M. fortuitum, M. avium, M. marinum, M. ulcerans)

Front 44

Non-tuberculosis Mycobacterium species

Back 44

- Rapid growers:
M. fortuitum - skin abscesses

- Slow growers:
Mycobacterium avium complex - fever, night sweats, weight loss, abdominal pain, tiredness, and diarrhea. About 20 to 30 percent of people with AIDS get MAC.
M. marinum - skin granuloma
M. ulcerans - severe skin ulcers

Front 45

Mycobacterium leprae

Back 45

- Causative agent of leprosy
- Leprosy is an infection of the skin, peripheral nerves, and mucous membranes, leading to lesions, hypopigmentation, and loss of sensation.
- requires prolonged contact and occurs directly through intact skin, mucous membranes, or penetrating wounds
- M. leprae Can Not be cultivated outside of a host

Front 46

Lepromatous vs Tuberculoid Leprosy

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Tuberculoid leprosy: strong cellular immune response, few bacteria, few skin lesions, low infectivity

Lepromatous leprosy: strong antibody response, weak cellular response, skin lesions, extensive tissue destruction, nerve involvement, high infectivity

Front 47

The Mycobacterium tuberculosis complex (MTC) includes five species:

Back 47

1. M. tuberculosis
2. M. bovis
3. M. africanum
4. M. canetti
5. M. microti

Front 48

The greatest killer of all time

Back 48

TUBERCULOSIS


It kills more adults each year than AIDS, diarrhea, malaria, and other tropical diseases combined

Front 49

What are Mycolic acids?

Back 49

beta-hydroxy fatty acids with a long a-alkyl side chain

mycobacteria have the longest side chains

Front 50

Number of people in the world infected with M. tuberculosis

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2 billion people or 1/3 of the world’s population

Front 51

annual number of deaths that are attributed worldwide to tuberculosis

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3 million

Front 52

M. tuberculosis pathogenicity

Back 52

1. phagocytized by aveolar macrophages
2. prevents fusion of phagosome with lysosome
3. Phagosome can fuse with other intracellular vesicles to gain nutrients and replicate
4. inactivates reactive oxygen and nitrogen species to evade killing
5. Tissue necrosis due to host cellular immune response

M. tuberculosis does NOT express toxins, its virulence comes from the ability to survive and replicate intra-cellularly

Front 53

miliary TB

Back 53

a form of tuberculous infection in the lung that is the result of erosion of the infection into a pulmonary vein, and the resulting spread of infection to the liver, spleen, etc

Front 54

The classic symptoms of pulmonary TB are...

Back 54

chronic cough with blood-tinged sputum, fever, night sweats and weight loss.

Front 55

What percentage of individuals who become infected with TB subsequently develop clinical disease?

Back 55

10 - 15%

Front 56

Legionella

Back 56

- facultative intracellular parasite
- The only documented source of Legionella species is water
- infections begins with a supply of water containing Legionellae and with a means for dissemination to humans (often aerosols)
- Infection begins in the lower respiratory tract
- Alveolar macrophages engulf the bacteria
- The bacilli multiply within the phagosome
- Treatment is with erythromycin and rifampin

Front 57

Legionella pneumophila

Back 57

- Gram-negative thin bacilli
- Posess pili (fimbriae) and are motile by means of a single polar flagellum.
- Most common cause of Legionellosis

Front 58

Corynebacterium

Back 58

- Gram positive rod-shaped (club shaped, or pleomorphic)
- aerobic or facultative
- Not encapsulated
- Non-motile
- Non-spore forming
- irregularly staining
- catalase-positive
- For the most part they are considered commensals
- Many species have volutin granules
- Produce Corynemycolic acids
- Contain Trehalose Dimycolate in the cell wall

Front 59

is the only true coryneform organism in the oral cavity

Back 59

C. matruchotii

Front 60

Respiratory Diphtheria is caused by toxigenic strains of...

Back 60

Corynebacterium diphtheriae

Front 61

What are Diphtheriods

Back 61

Bacilli that morphologically resemble C. diphtheriae

Commensals and opportunistic infections

Front 62

What are Propionibacteria?

Back 62

Obligate anaerobic Gram positive bacilli

Often classified as diphtheroids

Part of normal skin flora and can be found in dental plaque

Front 63

C. diphtheriae pathogenicity

Back 63

- Does not invade tissues away from the site of thelesion; instead produces diphtheria toxin
- DT is an A-B type toxin. It acts to inhibit eukaryotic protein translation by ADP-ribosylating EF-2
- There is an effective vaccine against the inactivated DT, immunity mediated by IgG

Front 64

Diptheria Toxin

Back 64

- A-B type toxin.
- ADP-ribosylates EF-2, using NAD as a donor.
- receptor for DT is HB-EGF
- After binding the receptor, DT is endocytosed and then the A subunit is transferred to the cytoplasm where it acts on eEF-2.
- A modified histidine called diphthamide is modified
- DT is encoded on the genome of specific bacteriophages (such as corynephage b)
- The presence of Iron represses production of DT

Front 65

The Schick test

Back 65

skin test of antibody reaction to standard dose of Diptheria toxin

Front 66

Treatment of Diphtheria

Back 66

- Supportive therapy to maintain airway
- Diphtheria Antitoxin: Produced in horses, In the US it is only available from the CDC, Neutralizes only unbound toxin
- Treatment with antibiotics: Penicillin or erythromycin, Treatment has little effect on toxin dissemination

Front 67

Corynebacterium is a genus within the family...

Back 67

Mycobacteriaceae

Front 68

What is listeriosis?

Back 68

A serious infection caused by eating food contaminated with the bacterium Listeria monocytogenes.


Many antibiotics are effective against L. monocytogenes
(ampicillin)

Front 69

Listeria monocytogenes

Back 69

- Gram-positive rod
- Facultative anaerobe
- Motile
- Food borne opportunistic pathogen
- Not encapsulated
- Not spore-forming
- Natural habitat is decomposing plant matter, in which they live as saprophytes
- Able to multiply at refrigeration temperatures
- Outbreaks occur in refrigerated ready-to-eat products that are eaten without cooking or reheating

- Virulence:
::Intra-cellular growth
>Internalin – Host cell invasion
>listeriolysin O (LLO) - Escape from the phageosome
>Phospholipases - escape from the phageosome
>ActA - induces actin polymerization and bacterial motility. Use actin to propel from one cell to another.
>Growth inside cells limits exposure to the immune system

Front 70

The only spore-forming organisms covered in our Micro course

Back 70

Bacillus
Clostridium

Front 71

Bacillus

Back 71

- Gram positive
- Forms spores
- Aerobic
- Soil dwellers world-wide
- Only B. anthracis is a strict pathogen (B. cereus can be)

Front 72

Initiation of sporulation depends upon activity of a “Two-component regulatory system” known as the...

Back 72

Sporulation Phosphorelay

Front 73

Bacillus Anthracis

Back 73

- Causative agent of Anthrax 
- Virulence factors include capsule and anthrax toxin 

Front 74

The Anthrax Toxin

Back 74

3 components:
1.PA = Protective antigen(the “B”)
2. LF = Lethal factor (an “A”)
3. EF = Edema factor (a different “A”)


- Components encoded on large plasmid, synthesized and secreted separately

- PA binds to receptor. Membrane protease cleaves PA. Seven copies of cleaved PA combine to form a donut-shaped heptamer. Up to three copies of EF or LF bind to heptamer and they are endocytosed.

- Targets of toxin: Cellular signalling

- EF binds calmodulin and makes cAMP

- LF is a metalloprotease that cleaves MAPKK’s

Front 75

Bacillus cereus

Back 75

- Produces an enterotoxin that causes food poisoning
- usually associated with eating contaminated rice.
- Rice contaminated with spores, improperly cooked = Spores germinate, grow, make enterotoxin

Front 76

Clostridium

Back 76

- Gram positive
- Spore forming
- Anaerobic
- Ubiquitous in soils
- Part of normal flora of GI

- Major Pathogenic Clostridia:
C. botulinum (botulism)
C. tetani (tetanus)
C. perfringens (gas gangrene)
C. difficile (diarrhea)

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Botulism

Back 77

- Due to toxin(s) produced by C. botulinum

- Three types:
1. Food-borne: C. botulinum in food, grows & makes toxin.
2. Infant: spores ingested, C. botulinum grow in GI tract, produce toxin
3. Wound: spores get into wound, grow.

- All types result in Flaccid Paralysis due to toxin attack on neurons at neuromuscular junctions

- C3 toxin
::ADP-ribosylates a G-protein 

- C2 toxin
:: targets cholinergic peripheral nerves
:: “A-B” type
:: ADP-ribosylates actin.
::The most potent toxin known
:: B component binds neurons at N-M junctions
:: A is a zinc-endopeptidase that cleaves SNARE components of the neuronal secretory pathway
:: Prevention of neurotransmitter (acetylcholine) release = flaccid paralysis

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Tetanus

Back 78

- Caused by A-B type neurotoxin produced by C. tetani
- targets CNS inhibitory synapses
- Spastic muscle contractions

Front 79

C. perfringens

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- Causes Gas Gangrene 
- Wounds infected by spores
- Spores germinate, grow, produce toxins 
- Massive tissue damage
- Ingestion of contaminated food can produce a self-limiting form of gastroenteritis.

Front 80

C. difficile

Back 80

- Causative agent of “antibiotic-associated” gastrointestinal diseases (pseudomembranous colitis and diarrheal disorders)
- Part of normal flora of 5-10% of general population
- Antibiotic therapy for infection by other organisms reduces major anaerobic flora; C. difficile population unchecked and proliferates
- Produces exotoxins which cause diarrhea, can lead to ulceration of colon and even death
- Produces two A-B toxins
- Both are UDP-glucosyl transferases
- Target GTPases that regulate synthesis of the actin cytoskelton.

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Helicobacter

Back 81

- Gram negative curved rod
- Causes peptic ulcers
- Differentiation from Campylobacter based on a strong urease positive test
- Prevalence ~40% in US, >80% in developing countries
- 1/10 Americans suffers from peptic ulcer disease during their lifetime
- Pathogenesis:
::Colonizes the mucus layer of stomach.
::Progressive destruction of mucosa & ulcer formation
::Adherent and non-adherent phases
:: Evasion from host defenses not fully understood
:: the most genetically diverse bacterial species
:: Virulence factors
Adhesins
Cytotoxin
Endotoxin
Flagella – allow bacteria to penetrate through gastric mucous
Mucinase –degrades gastric mucous, exposing gastric epithelium to gastric acid
Urease - raises the pH

- Treatment:
:: Triple Therapy - Proton pump inhibitor, amoxicillin and clarithromycin. eradication of the organism in >80% of individuals

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Vibrionaceae

Back 82

- Gram negative comma-shaped rod
- Most species motile, polar flagellum
- Grows in salt and fresh water
- 3 species are pathogens of humans:
1. Vibrio cholerae
2. Vibrio parahaemolyticus
3. Vibrio vulnificus

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Vibrio cholerae

Back 83

- 2 distinct circular chromosomes
- Serotypes O1 and O139 cause cholera
- Transmitted by fecal-oral route
- Endemic in areas of poor sanitation
- May persist in shellfish or plankton

- Pathogenesis:
:: High infectious dose required
:: Colonization of proximal small bowel
:: Secretion of cholera toxin
:: Phage-encoded A-5B toxin
:: B binds to GM1 ganglioside on enterocytes
:: A enters cell, separates into A1, A2
:: A1 inactivates GTPase of Gsa protein that regulates adenylate cyclase (AC), AC stuck “On” position
:: 100 fold increase in cAMP
:: Cl- efflux causes water secretion

Front 84

Cholera

Back 84

- Disease spectrum from asymptomatic to severe (cholera gravis)
- victim may die within 2-3 h of onset of symptoms
- Profuse watery diarrhea (~1 l per hr)
- Major symptoms caused by loss of water and electrolytes
- Mortality rate without treatment: 50%-60%

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Vibrio parahaemolyticus

Back 85

- Leading cause of seafood-borne bacterial gastroenteritis
- Mostly watery diarrhea, cramps, nausea, vomiting, self-limited (~3 days)

Front 86

Vibrio vulnificus

Back 86

- Most common Vibrio disease in US
- Causes 95% contaminated seafood-related deaths
- Wound infection, e.g. cleaning crabs

- Pathogenesis
:: Antiphagocytic
:: Stimulates release of inflammatory
cytokines
:: LPS
:: Extracellular enzymes (Proteases, collagenase, phospolipases, elastase, etc)
:: Siderophores sequester iron from hemoglobin

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Spirochetes

Back 87

- Gram-negative, long, slender, helically-shaped
- Motile via axial filaments
- Difficult to Gram stain and view

Three groups we covered:
1. Treponema
2. Borrelia
3. Leptospira

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Treponema pallidum

Back 88

- Agent of Syphilis

- Transmission is by:
:: direct contact with lesions
:: 90% by sexual contact
:: congenital transfer

- Symptoms occur in stages
:: primary - hard chancre: single lesion on cutaneous/ mucous membrane surface; appears in 3 weeks/disappears 4-12 weeks
:: secondary - Cutaneous & mucous membrane lesions for weeks to months, macular skin rash, infectious stage
:: latent - noninfectious stage/may last a lifetime or result in tertiary syphilis
:: tertiary - Non-infectious stage, granulomas due to host response, Saber shin syndrome, Neurosyphilis, transplacental transmission during latency



- Virulence factors
:: Protection from immune response by cloaking with host proteins
:: Fibronectin binding

Front 89

Borrelia

Back 89

- Gram negative curved rod
- Microaerophilic-to-anaerobic
- Loose, irregular coils
- Highly-adapted to arthropod transmission

- B. hermsii - Relapsing fever
chills, fever, asymptomatic, 5-14 days between relapses…
Transmitted animal-to-animal, animal-to-human by ticks, human-to-human by lice

- B. burgdorferi – Lyme disease
stage 1: “Bulls eye”, headache, fever, muscle aches
stage 2 (weeks-months): chronic disease, arthritis, muscle pains, rare CNS signs, cardiac damage. Antibiotics for 3-4 weeks with doxycycline or amoxicillin generally effective in early disease

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Leptospira interrogans

Back 90

- Gram negative curved rod
- Spread by animal and urine/water contamination
- Causes Skin/mucosal surface abrasions, chills, headache, severe muscular pain, infectious jaundice
- Treatment: penicillin, tetracycline

Front 91

Families of DNA viruses

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Poxviridae: smallpox virus, monkeypox virus

Herpesviridae: Herpes simplex virus (types 1 and 2), Epstein-Barr virus, cytomegalo virus, human herpes virus 6,7,8

Adenoviridae: Adenovirus

Hepadnaviridae: Hepatitis B virus

Polyoma viridae: BK virus, SV40

Papilloma viridae: Papilloma virus

Parvoviridae: Parvovirus B19

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Sizes of viruses range from...

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18nm to 300 nm

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Families of RNA viruses

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Paramyxoviridae: measles virus, mumps virus, metapneumovirus

Orthomyxoviridae: Influenza virus types A, B, C

Coronaviridae: Coronavirus, SARS

Rhabdoviridae: Rabies virus

Retroviridae: Human T-cell leukemia virus types I and II, Human immunodeficiency virus

Picornaviridae: Poliovirus, hepatitis A virus

Togaviridae: Rubella virus

Flaviviridae: Yellow fever virus, West Nile virus, Hepatitis C virus

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Viral structure: Naked Capsid

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Component: Protein

Properties: Environmentally stable to temperature, acid, proteases, detergents,
drying. Released from cell by lysis

Consequences:
Can be spread easily
Can dry out and retain infectivity
Can survive the adverse acidic conditions of the gut
Antibody may be sufficient for immunoprotection

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Viral Structure: Envelope

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Components: Membrane, Lipid, Protein, Glycoprotein's

Properties: Environmentally labile – is disrupted by acid, detergents, drying, heat
Modifies cell membrane during replication
Is released by budding and cell lysis

Consequences: Must stay wet. Cannot survive the gastrointestinal tract
Spreads in large droplets, secretions
Does not need to kill the cell to spread
May need antibody and cell-mediated immune response for protection and control
Elicits hypersensitivity and inflammation to cause immunopathogenesis

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Properties of DNA viruses

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DNA is not transient or labile

Viral genomes remain in the infected cell

Many DNA viruses establish persistent infections

DNA genomes reside in the nucleus (except for pox virus)

Viral genome resembles host DNA for transcription and replication

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Properties of RNA viruses

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RNA is labile and transient

Replicate in the cytoplasm

Cells cannot replicate RNA.

RNA viruses must encode an RNA dependant RNA polymerase

Prone to mutation

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Attachment region of Influenza virus binds to ____ _____ domains expressed in various types of cells

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sialic acid

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Inhibitors of Viral proliferation:

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Antibody – before entering the cell binds to the viral proteins

Nucleoside analogues: inhibit the replication, DNA synthesis

Protease inhibitors: inhibit assembly of virus from a polyprotein segment

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Prodrome

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non specific early symptoms of viral infection

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Arboviruses:

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Viruses which are transmitted by arthropod vectors

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nucleoside analogues as antiviral agents

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Examples: 1) Acyclovir (analogue of guanosine) 2) Azidothymidine (analogue of thymidine)

AZT is 100 fold more sensitive to viral reverse transcriptase than to the host cell DNA polymerase

Mechanism of action: Nucleoside analogues inhibit viral DNA polymerase selectively

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Syncytium:

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Multinucleated giant cell formed by viral fusion of individual cells

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CPE of HSV infection:

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HSV infected cells become rounded and multinucleated. They lose the monolayer

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Tissue culture dose (TCD50):

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Titer of virus that cause cytopathologic effects in half the tissue culture cells

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Lethal dose (LD50):

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Titer of virus that kills 50% of a set of test animals

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Infectious dose (ID50):

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Titer of virus that initiates a detectable symptom, antibody or other response in 50% of a set of test animals

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Number of infectious viruses can be evaluated with a count of the...

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plaque forming units (PFU)

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General Characteristics of AIDS

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Appears to have evolved from a simian virus during 1930s\

The 4 H club of risk groups – homosexual men, hemophiliacs, Haitians, heroin addicts

Caused by Human immunodeficiency virus

Enveloped positive strand RNA Retrovirus

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Life cycle of HIV

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HIV binds to CD4 and chemokine receptors

Enters the cell by fusion

Synthesizes DNA (provirus)

Incorporates into the chromosome

Transcription factors of the host cell takes over

The virus assembles at the plasma membrane

Matures after budding from the cell

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HIV infection

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Gp 120 and gp 41 help the virus to bind to the CD 4 receptor

Chemokine receptors (CXCR4) facilitate the binding and bring them closer to each other

Enveloped spherical virion loses its envelope upon entering the cell

First a negative strand of DNA is synthesized by reverse transcriptase


Mutation rate – 1 in 2000 bases

Causes antigenic drift which helps the virus to escape the immune system

Virus has tropism for CD4 expressing T cells and macrophages

Pathogenesis:
::Lytic and latent infection of CD4 T cells by HIV
::Persistent infection of monocyte macrophage family
::Disrupts neurons
::Results in Immunodeficiency and Dementia


80% intravenous drug users are positive for HIV antibody

HIV 2 is less severe than HIV 1

Anal sex has more chances of infection

5 million new infections every year

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Hepatitis

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A, B : classical hepatitis virus

C, D, E, G : hepatitis viruses

Contagious

1/3 of the world population is infected

1-2 million death per year

Death rate is coming down due to HBV subunit vaccine

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Hepatitis A Virus

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Picornavirus

Single stranded +RNA genome

Fecal oral route of infection
Capsid does not have envelope

Capsid resists stomach acids


Rarely fatal
1 to 3 out of 1000 infected develop-
-fulminant hepatitis

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Hepatitis B Virus

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Hepadna virus

Enveloped virion contains double stranded circular DNA

3 month incubation period
Spread by needle, blood or sex

Chronic hepatitis in 5% to 10%

HBV replicates through a RNA intermediate

After entry into cell the double stranded DNA genome is completed

DNA moves into nucleus
Integrates to host chromosome
Transcribes mRNA and a genomic RNA

The core of capsid contains RNA dependant DNA polymerase which synthesizes DNA


80% of all primary hepatocellular carcinoma are HBV infected

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The delta hepatitis virion

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- Circular ssRNA
- Hepatitis B virus (HBV) surface coat enclosing Hepatitis D virus (HDV) genome

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herpes simplex virus

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Large enveloped viruses containing linear double stranded DNA

HSV-1 causes syndromes mainly in the upper part of the body

HSV-2 causes syndromes in the genital area

Site of herpes simplex Viral latency:
Trigeminal ganglia

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Vericella-zoster virus (Human herpes virus 3) causes...

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chicken pox

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Epstein-Barr virus

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Human Herpes virus 4


Primary target: B cells and epithelial cells

) infection may be asymptomatic or may produce the symptoms of mononucleosis. The incubation period can last as long as 2 months.

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cytomegalovirus

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Human herpes virus 5


The outcome of CMV infection depends very heavily on the immune status of the patient.

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human herpes virus 6

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Causes exanthema subitum (roseola)

High fever after ~4 days

Then rash without fever develops before recovery

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Orthomyxoviridae:

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Influenza A, B, C (A and B are pathogenic)

Enveloped, having a negative sense RNA genome

Only influenza A undergo reassortment
Unlike for most other RNA viruses, transcription and replication for Influenza A occur in the nucleus

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Neuraminidase

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antigenic glycosilated enzyme helps in release of viruses

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Zanamavir and Oseltamivir:

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inhibit neuraminidase of Influenza A and B

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Amantadine and rimantadine:

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inhibit un coating step in influenza A infection.

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Human Papilloma virus(HPV)

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Double stranded circular DNA

Genome replicated and assembled in Nucleus
40% of healthy people have HPV in their oral mucosa

Dentists can be infected

Passed by contact

Can cause warts and cell transformation in the hand,foot, throat and cervix.

Vacuolated cytoplasm is characteristic of HPV infection

Can cause proliferation and keratinization of epithelial cells

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Adenovirus

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Double stranded DNA viruses

Virions are nonenveloped

Common disorders: respiratory tract infection, conjunctivitis, hemorrhagic cystitis and gastroenteritis

Common method of Transmission: respiratory droplets

Inefficient assembly of virions: basophilic bodies containing DNA, proteins and capsids

Conjunctivitis caused by adenovirus

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Pox viruses

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Largest and most complex viruses

Contain linear double stranded genome

DNA viruses replicate in the cytoplasm

Include human viruses variola (small pox) and molluscum contagiosum

Spread by Inhalation

Primary viremia: causes infection to spleen, bone marrow, lymph nodes, liver and all organs followed by the skin (rash).
Secondary viremia: causes the development of additional lesion throughout the host followed by death or recovery

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Parvovirus

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Mechanism of spread of parvovirus within the body: Inhalation>Replication in bone marrow>viremia


Mild flu like – Erythema infectiosum

Hemolytic anemia

). The internalized parvovirus delivers its genome to the nucleus, where the single-stranded (plus or minus) DNA is converted to double-stranded DNA by host factors and DNA polymerases present only in growing cells. Transcription, replication, and assembly occur in the nucleus. Virus is released by cell lysis

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Picornaviridae

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Largest family of viruses.

Human enteroviruses and rhinoviruses

Non-enveloped RNA viruses with capsids

Best known and most studied picorna virus- Poliovirus

Most viruses are cytolytic

Genome is translated as a polyprotein

Cleaved by viral encoded proteases into individual proteins

+ sense RNA with poly A tail

The genome is sufficient to infect a host cell

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Poliovirus

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Enterovirus

Produce a protease that blocks the translation of most
Cellular mRNA

Viruses reach brain through skeletal muscle
Nerves. Cytolytic to motor nerves causing paralysis. Number of neurons killed
will determine whether paralysis will occur.

Resists stomach acid/bile/proteases
Portals of entry: upper respiratory tract, oropharynx and the intestinal tract
Viral replication is initiated in the mucosa and lymphoid tissue of tonsils and pharynx. Subsequently infects lymphoid cells of Peyer’s patches
Enterovirus are shed in feces for long time
Nature of disease correlate with age of person
Transmission: fecal oral route

90% polio virus
Infection – non
Symptomatic

21,000 cases / year during pre vaccine era
18 cases / year in non vaccinated patients

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Rhinovirus

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Most prevalent cause of common cold

restricted to upper respiratory tract

Binding of the ICAM-1 molecule within the canyon of the virion triggers the opening of capsid for release of the genome into the cell.

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Coxsackie A virus: Herpangina

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Infectious disease in children

Characterized by a sudden occurrence of fever, loss of appetite

Inflammation and ulceration of throat

Distinct vesicles on the palate

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Coxsackie A virus:

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Hand-foot-and-mouth disease

Vesicular lesions on the hands,feet, mouth and tongue

First develops in the oral cavity

Within one day spreads to other parts

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Corona viridae:

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Second most prevalent cause of the common cold

Prefers to proliferate in upper respiratory tract

In 2002 outbreak of severe acute respiratory syndrome (SARS)
Enveloped virions

Contains long positive (+) RNA genome

No DNA formation

Two phases of translation:
1. Early phase: translation of RNA dependent RNA polymerase.
2. late phase to produce structural and non structural proteins.

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Paramyxoviridae:

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Measles, mumps and parainfluenza virus

Virus induce cell-cell fusion causing multinucleated giant cells

Transmitted in respiratory droplets and initiate in the respiratory tract

Cell mediated immunity causes many of the symptoms but essential for control of the infection

The virus binds to glycolipids or proteins and fuses with the cell surface. Individual mRNAs for each protein and a full-length template are transcribed from the genome. Replication occurs in the cytoplasm. The nucleocapsid associates with matrix and glycoprotein-modified plasma membranes and leaves the cell by budding

Mumps virus:
infects epithelial cells of respiratory tract, Spreads systematically by viremia, then Infects parotid gland, testes and central nervous system. Principle symptom is swelling of parotid glands caused by inflammation

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Togaviruses and Flaviviruses

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Togaviruses: Alpha viruses, Rubiviruses (rubella virus)

Flaviviruses: (West Nile viruses)

Arboviruses: Alpha viruses and Flaviviruses

Enveloped positive single stranded RNA viruses

Transmitted through Arthropods

Disease syndromes of the alphaviruses and flaviviruses: DHF: Deng hemorrhagic fever (loss of fluids from vasculature)
DSS: Deng shock syndrome

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Spread of rubella virus within the host

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Rubella enters and infects the nasopharynx and lung

Spreads to the lymph nodes and monocyte-macrophage system

Circulating antibody can block the transfer of virus

Immunologically deficient pregnant woman, the virus can infect the placenta and spread to the fetus

Can cause serious congenital abnormalities in the child