Week 2 Flashcards
MacConkey agar
inhibits gram + bacteria, lactose fermenters become pink/purple
EMB agar
methylene blue inhibits gram + bacteria, lactose fermenters become dark purple/black (E. coli is green)
Salmonella
oxidase \_\_\_\_\_ gram \_\_\_\_\_\_\_ ferments \_\_\_\_\_\_ Lac \_\_\_\_\_ Invasive or noninvasive? infects what part of GI tract?
oxidase -
gram -
ferment glucose
Lac -
INVASIVE
Small intestine
Typhoid fever
Caused by salmonella Typhi infection
1) enteric fever, systemic disease, fever
2) Human adapted - Colonizes gall bladder → carrier state or intestinal perforation
3) Constipation or inflammatory diarrhea –> Stepwise increase in temperature to high fever
4) 1-3 weeks incubation
- Can continue for 6-8 weeks
5) Can kill immunocompetent people
6) Has a capsule that helps with immune evasion
TX = abx
Non-typhoidal salmonella infection
Fecal-oral transmission from poultry, eggs, contaminated fresh produce
Febrile food poisoning 24-48 hrs after ingestion
Nausea, vomiting, headache, chills, fever, cramps, watery diarrhea
High neutrophils
Self-limited - no abx required
Can cause disseminated disease in HIV patients
Salmonella
Toxins/Virulence Factors
TYPE III SECRETION SYSTEM
1) Invasion via M cells with type III secretion system → transient bacteremia
2) Uptake by phagocytes (macs) via different type III secretion system → salmonella multiply
Typhoid vaccine
purified Vi polysaccharide (adults and children > 2 yrs)
Shigella
gram \_\_\_\_\_\_ oxidase \_\_\_\_\_ ferment \_\_\_\_\_\_ Lac \_\_\_\_\_\_\_ Invasive or noninvasive? Infects what part of GI tract?
Gram - Oxidase - Ferment glucose Lac - INVASIVE Large intestine
What is the infective dose of shigella?
Requires SMALL infective dose (very acid resistant)
Shigella diarrhea
inflammatory diarrhea, dysentery
Fever, malaise, vomiting, watery diarrhea → frank dysentery (frequent small stools with blood/mucus, cramps, tenesmus)
Humans are only known reservoir → fecal-oral from person to person (Food, fingers, feces, flies)
Can cause HUS (S. dysenteriae)
Incubation time for Shigella
Incubation 1-4 days
Shigella
Toxins/Virulence Factors: (2)
1) ENTEROTOXIN –> produce watery diarrhea
2) TYPE III SECRETION SYSTEM
Type III secretion system in Shigella mechanism of invasion and spread
ntry via M cells, uptake by macrophages → induce apoptosis and inflammation (IL-1/IL-8)
Invade basal side of epithelial cells, lyse vacuole, grow in cytoplasm, spread directly into neighboring cells
Only S. dysenteriae (type 1) make cytotoxic Shiga toxin
E. Coli
gram \_\_\_\_ shape? Ferment \_\_\_\_\_ Oxidase \_\_\_\_\_ Lac \_\_\_\_\_
Gram - rod ferments glucose oxidase - lac +
ETEC (Enterotoxigenic)
Diarrhea
traveler’s diarrhea, severe watery, no blood/pus, abdominal cramps, vomiting
Toxigenic, NONINVASIVE
Infects small intestine
ETEC (Enterotoxigenic)
Toxins/Virulence factors (3)
1) Heat labile enterotoxin
2) Heat stable enterotoxin
3) Fimbrial adhesins → colonize small intestine
ETEC (Enterotoxigenic)
Treatment
supportive, fluid replacement
Do NOT use abx
Heat labile enterotoxin
Present in ETEC
similar to CHOLERA TOXIN but binds to different gangliosides (different B-subunit) than cholera → target different populations
Heat stable enterotoxin
Present in ETEC
small peptide toxin, activates guanylate cyclase → increased cGMP → increase fluid secretion
EHEC: Enterohemorrhagic
Diarrhea
bloody, hemorrhagic colitis, dysentery
INITIAL WATERY diarrhea → grossly BLOODY
Fever can be seen
Fecal leukocytes uncommon **
Primarily toxigenic - NONINVASIVE
Infects large intestine
EHEC: Enterohemorrhagic
Infectious dose?
Incubation period?
Possible complications?
Requires only small infectious dose (acid stable)
3-9 days of incubation
Can cause Hemolytic Uremic Syndrome (HUS)
EHEC: Enterohemorrhagic
most common serotype
O157:H7 serotype = colorless colonies on sorbitol-MacConkey media (does NOT ferment sorbitol)
EHEC: Enterohemorrhagic
Treatment
supportive
NO abx
abx → increase risk of HUS by increasing expression of shiga-like toxin
EHEC: Enterohemorrhagic
Toxins/Virulence Factors:
1) Attaching and effacing
2) Shiga-like cytotoxins Stx-1 and Stx-II
Shiga-like cytotoxins Stx-1 and Stx-II
chromosomally encoded by lysogenic toxin-converting bacteriophages
Stx binds Gb3 sphingolipids of enterocytes and renal endothelial cells
Stx-A subunit → binds rRNA → inhibit protein synthesis → tissue damage
EPEC: Enteropathogenic
Diarrhea
watery, persistent diarrhea in infants (<1yr), no blood/mucus, no tissue invasion, vomiting, low grade fever, prolonged, can have relapse
NON INVASIVE
EPEC: Enteropathogenic
Treatment
rehydration, responsive to abx
EPEC: Enteropathogenic
Main toxin/virulence factor
Attaching and effacing (AE)
-TYPE III SECRETION SYSTEM
Attaching and effacing toxins
Present on EHEC and EPEC
1) Adhere to enterocyte surface
2) **Type III secretion system secretes intimin receptor → microvilli destruction, pedestal formation → interferes with absorption
Yersinia spp:
Gram _____
Oxidase ____
ferment _____
Infects what part of GI tract?
Gram -
Oxidase -
Ferment glucose
Infects small intestine
Yersinia spp:
disease
Associated with eating undercooked pork, dairy products
Disease: low grade fever, watery diarrhea + some blood + fecal leukocytes
Infects terminal ileum
RLQ pain → MIMIC APPENDICITIS
Can cause reactive arthritis (especially in HLA-B27)
ABX not very effective
Vibrio cholerae
Gram _____
Oxidase ____
Invasive or noninvasive?
Infects what part of GI tract?
Gram -
Oxidase +
NONINVASIVE
Infects SMALL INTESTINE
Vibrio cholerae
Diarrhea
Non invasive diarrhea - profuse, watery, “rice water”
Caused by ENTEROTOXIN (primarily toxigenic)
2-5 day incubation period
Abrupt onset diarrhea, abdominal cramps, vomiting - NO FEVER
Vibrio cholerae
Treatment
fluid replacement + abx (can shorten infection)
Vibrio cholerae
1) Enterotoxin - Cholera Toxin
2) TCP Pilus
Cholera Toxin
BACTERIOPHAGE (CTX) conversion is important, uses TCP pilus to transfer toxin gene
Has A-B type toxin
Cytotonic (does NOT kill the cell)
A-B type toxin
Cholera toxin
B-subunit: binds to cell surface receptors (ganglioside GM 1) of enterocytes
A-subunit: enters cell cytoplasm, transfers ADP-ribose from NAD to G-protein → constitutive activation of adenylate cyclase → increase cAMP → Cl- secretion → fluid loss
TCP Pilus
Cholera toxin
surface-expressed adherence factor (toxin coregulated pilus)
Transmission of cholera
Fecal-oral transmission (water, contaminated foods, shellfish)
Vibrio parahaemolyticus
in salt water
Gastroenteritis, wound infections, septicemia
Associated with raw/undercooked shellfish
Can produce bloody stools → produces hemolysin
Vibrio vulnificus
gastroenteritis/wound infections from contaminated seafood (oysters) and extraintestinal infections in immunocompromised
Campylobacter
gram \_\_\_\_ size and shape? oxygen requirement? Temperature requirement? Oxidase \_\_\_\_ Catalase \_\_\_\_\_ Ferment \_\_\_\_\_
Gram - small, curved rod microaesophilic Grows best at 42 C Oxidase + Catalase + Ferments glucose
Dose requirement for Campy infection?
Low dose required for infection
Campylobacter
diarrhea
diarrhea, fever, abdominal cramping, +/- bloody stools +/- fecal leukocytes
Invades terminal ileum and proximal colon
Food borne gastroenteritis (poultry, milk, water, pets)
Most common cause of gastroenteritis in Western world
Complications of Campylobacter infection (2)
1) Guillain-Barre syndrome - molecular mimicry between LPS antigen and GM1 ganglioside = ASCENDING paralysis
2) Reiter’s syndrome (autoimmune reactive arthritis) possible (especially HLA-B27)
Treatment of Campylobacter
fluid replacement, abx in severe cases (erythromycin, quinolones)
Helicobacter
Gram \_\_\_\_ shape? Motility? oxidase \_\_\_\_ urease \_\_\_\_ ferment \_\_\_\_\_\_ Oxygen requirements Isolated on \_\_\_\_\_\_\_ agar
gram - curved, rod highly motile oxidase - Urease + Ferments glucose Microaerophilic
Isolated on Campy agar
Helicobacter
Disease
gastritis, gastric/duodenal ulcers, gastric adenocarcinoma, MALToma
MOST common human bacterial pathogen
Colonizes mucous layer of stomach - does NOT invade
Causes mucosal inflammation, epithelial cell damage, and neutrophil infiltration
Helicobacter
Treatment
Triple therapy: PPI + amoxicillin + clarithromycin x 14 days
LPS (lipopolysaccharide)
in outer membrane of all gram neg bacteria
Made up of Lipid A + core polysaccharides + O antigens
Lipid A
toxic part of LPS (endotoxin), outer layer
Core polysaccharides
constant region of LPS within a genus
O antigens
repeating subunits of oligosaccharides, variable, used for species identification
H antigens
flagella (motile organisms only)
K antigens
capsular polysaccharide (increases virulence, not in all strains)
Watery diarrhea
symptoms
what part of GI tract affected
4 bugs
copious, watery, no blood or pus, no tissue invasion, in small intestine
Small intestine disease usually secretory diarrhea
→ ETEC, EPEC, Campylobacter, Vibrio cholerae
Dysentery
symptoms
what part of GI tract affected
4 bugs
scant volume, blood/pus/mucus present, tissue invasion
in large intestine
→ Shigella, Entamoeba histolytica, EIEC, Campylobacter
Protracted diarrhea
lasting > 14 days
→ EPEC
Bloody, watery diarrhea
symptoms
what part of GI tract affected
3 bugs
copious, some blood/pus, invasion
in Ileum or colon
Salmonella, Campylobacter, Yersinia
Hemorrhagic colitis
symptoms
what part of GI tract affected
1 bug
copious, like liquid blood, no leukocytes/ invasion, in large intestine
→ EHEC
Large intestine infection typically inflammatory
2 bugs that require high infectious dose
2 bugs that require low infectious dose
More sensitive to acid → requires higher infective doses
Vibrio, ETEC
Resistant to acid → requires low infective dose
Shigella, Salmonella
4 bugs that cause noninvasive diarrhea
V. Cholera, ETEC, EHEC, EPEC
3 bugs that cause invasive diarrhea
Shigella, Salmonella, S. Typhi
Produce inflammatory diarrhea + frequent/low-volume/mucoid/bloody stools + tenesmus + FEVER + abdominal pain + MANY LEUKOCYTES
Sheets of leukocytes in stool indicative of colonic damage
Zipper model
tight interaction between bacterial cell surface ligands and host cell receptors → host cell surface closes around bacterium
3 bugs that use the zipper model
1) Parasite induced phagocytosis (Listeria)
2) Receptor-mediated phagocytosis of macrophages (TB)
3) Coiling phagocytosis (Legionella)
Trigger model
+ two bugs that use this
bacterial products induce cell surface to take up bacteria
Type III secretory systems cause this (Salmonella, Shigella)
Listeria
gram \_\_\_\_\_\_ Shape? Catalase \_\_\_\_\_ Spore forming? Hemolysis? Motility? Intracellular or extracellular?
Gram + Rod Catalase + Non-spore forming B-hemolytic TUMBLING motility extracellularly Facultative intracellular
Listeria grows at what temperatures? What things can you eat that are associated with Listeria?
Grows at refrigerated temperatures → poorly pasteurized milk/cheeses, deli meats, raw vegetables
How does listeria enter the body?
Uses “Zipper Mechanism” - penetrates GI mucosa, invades phagocytes → grows/spreads intracellularly
How does listeria replicate?
spreads cell to cell without exposure extracellular environment using actin-based cellular contractile mechanism (actin rocket)
NO exposure to antibodies, complement or neutrophils with cell-to-cell spread → Cell mediated immunity critical
2 main virulence factors of Listeria
1) Produces an endotoxin - only gram + organism with endotoxin
- Has tropism for nervous tissue → meningitis
2) Listeriolysin O bacterial toxin: digests phagosome allowing Listeria to infect target cell
How is listeria transmitted? (3)
Ingestion of bacteria in food
Placental transmission
Vaginal transmission
Susceptible populations for severe Listeriosis (meningitis and sepsis)
Susceptible populations = pregnant women, neonates, elderly, AIDS patients due to deficiency cell-mediated immunity
Consequences of Listeria bacteremia in pregnancy
3rd trimester amnionitis, preterm labor, spontaneous abortions, stillbirths
Granulomatosis infantiseptica
placental transmission of Listeria to infant → early onset sepsis, granulomas throughout body, rash
Listeria Infection in Immunocompetent person causes what?
febrile gastroenteritis
Treatment of Listeria
ampicillin, penicillin G, TMP-SMX +/- Gentamicin
Legionella
Gram \_\_\_\_\_ shape? Special stain? Intracellular or extracellular? Oxidase \_\_\_\_\_ Grows on what special agar? 2 important cofactors...
Gram negative rod (weak gram stain) Silver stain Facultative intracellular Oxidase + Grows on charcoal yeast extract with IRON and CYSTEINE
Transmission of Legionella
aerosols from environmental water sources (air conditioning, hot water tanks)
Two diseases caused by legionella infection
1) Legionnaire’s Disease
2) Pontiac fever
Legionnaire’s Disease
severe pneumonia, lobar
Nonproductive cough
Confusion, DIARRHEA
Signs of kidney damage (proteinuria, microscopic hematuria)
HYPONATREMIA - due to SIADH or renal tubulointerstitial disease impairing sodium reabsorption
Diagnosed by presence of ANTIGEN IN URINE
Pontiac fever
mild flu-like illness (fever, chills, fatigue, malaise, headache) WITHOUT respiratory symptoms
Treatment of Legionella infection
Macrolides (Azithromycin) + Fluoroquinolones (Levofloxacin)
How does legionella invade and replicate?
Enters respiratory tract, taken up by macrophages → inhibits phagosome-lysosome fusion → intracellular replication
Obligate intracellular organisms (5)
cannot reproduce outside cell
Chlamydia Coxiella burnetii Ehrlichia Mycobacterium leprae Rickettsia
Facultative intracellular organisms
capable of both intra and extracellular growth
1) Bartonella
2) Brucella
3) Francisella
4) Legionella
5) Listeria
6) Mycobacterium
7) Nocardia
8) Salmonella
9) Shigella
Aminoglycosides vs. Tetracyclines for treatment of intracellular organism infections:
Aminoglycosides (gentamicin): enters into cells via ________ → ___________ → accumulates in _________
Tetracyclines: enter into cells via ________ → action in ________
Aminoglycosides (gentamicin): enters into cells via PINOCYTOSIS → phagosomes fuse with lysosomes → accumulates in lysosomes
Tetracyclines: enter into cells via DIFFUSION → action in cytosol
Signs and symptoms of VIRAL gastroenteritis
ACUTE onset WATERY diarrhea (no blood/mucus) +/- vomiting
Nausea, intestinal cramping, muscle aches, low grade fever
Epidemiology of VIRAL gastroenteritis
incubation and duration?
shedding phase length?
transmission how?
Short incubation and duration of symptoms with prolonged asymptomatic shedding phase
Transmitted on surfaces, food, and water (STABLE)
Seasonal transmission
Person-to-Person or Fecal-Oral
Pathophysiology of viral gastroenteritis infection (4)
1) LOCAL infection of intestinal epithelial cells
2) MALABSORPTION due to virus killing mature enterocytes
3) Local VILLUS ischemia
4) Viral ENTEROTOXIN → transepithelial fluid loss
What is the best way to diagnose viral gastroenteritis?
Multiplex RT-PCR detection of viral nucleic acids in stool = most sensitive
RIA or ELISA for ab can tell if exposure occurred, not if there is active infection
Calciviruses (2)
1) Norovirus
2) Sapvirus
Norovirus
size?
enveloped?
genome? (DNA vs. RNA, etc.)
shape?
Small
non-enveloped
ssRNA (+ sense)
Cup shaped (chalice-like) indentations (golf ball)
Norovirus has ______ and _______ which causes antibody to only give short-term protection
strain diversity and antigenic shift
Individuals homozygous ____________ are highly resistant to norovirus infection
Individuals homozygous non-secretors of FUT2 are highly resistant to norovirus infection
Disease caused by Norovirus
⅓ infected are asymptomatic and shedding virus
Vomiting, watery diarrhea, nausea, cramping, malaise, headaches, myalgias, low grade fever
Quick on, quick off
Incubation, duration, and shedding of Norovirus infection
Incubation = 15 hrs - 2 days Duration = 1-2 days Shedding = up to 8 weeks
Norovirus infections are associated with which locations?
how is it spread?
Cruise ships, hospitals, nursing homes
Fecal-oral person-to-person transmission
Year round outbreaks (less seasonal as rotavirus)
Rota virus:
genome?
Shape?
Envelope?
Season of most infections?
11 genome segments of dsRNA + RNA-dependent RNA-polymerase (each encodes ssRNA that makes 1 protein)
Rota = Wheel
Non-enveloped
WINTER
Rotavirus protein shell is made up of what 3 layers?
1) Outer capsid layer: VP7 with VP4 spikes → acid stability, induces neutralizing antibody
2) Inner capsid layer: VP6
3) Innermost core: VP2
When two different rotaviruses infect the same cell, what happens?
Reassortment of genome when two different rotaviruses infect same cell
Rota virus virions are not infectious unless activated by _________
Trypsin
Rota virus causes what disease
Infects small intestine and replicates in villus epithelial cells → villous shortening and stunting
High viral titers shed in stool
Abrupt onset fever, vomiting, then diarrhea (explosive, nonbloody, watery)
Rota virus
incubation
duration
shedding
Incubation period: 1-3 days
Duration: 4-8 days, self-limited
Shedding can occur for > 3 weeks
Treatment of Rotavirus
is it preventable?
REHYDRATION
Preventable by vaccination
Rotavirus vaccine
RotaTeq: Pentavalent live bovine rotavirus vaccine
Rotarix: monovalent live human rotavirus vaccine
Associated with increased risk of intussusception
Diagnosis of Rotavirus
ELISA Rotazyme identification
Enteric Adenoviruses:
eveloped?
shape?
genome?
Non-enveloped
Icosahedral
dsDNA virus
Enteric Adenoviruses:
Diseases (2)
1) URI symptoms (conjunctivitis, pharyngitis, pneumonia, hemorrhagic cystitis) + gastroenteritis (serotypes 40 and 41)
2) Watery diarrhea, then vomiting lasting 5-12 days (longer than Nora/Rota) - persistent, but less severe
Astroviruses
size?
envelope?
genome?
shape?
Small, non-enveloped
ssRNA (+ sense)
Star shaped capsomers
Astroviruses
CAN be grown in cultures of _____________
Requires ________ to activate virus infectivity
CAN be grown in cultures of human intestinal epithelial cells
Requires trypsin to activate virus infectivity
HPV
main features
papillomavirus
Small, non-enveloped, icosahedral DNA virus
Two main structural proteins of HPV (late genes) and what they are used for
Major capsid protein L1 → basis of vaccine, outer part of virus
Minor capsid protein L2 → required to produce infectious virus particles
HPV Lifecycle/Invasion
Invades only undifferentiated proliferating basal cell layers in epithelium → Infect epithelium of skin, anogenital tract, and oropharyngeal mucosa
Replicates upon epithelial differentiation
Releases virus particles from fully differentiated skin layers
HPV
Transmission
sexual contact oral/genital and mother-newborn (vertical transmission)
Risk factors of HPV infection:
Early onset intercoars (before age 20) Multiple sexual partners History of genital warts Immunosuppressive disorders (HIV/AIDS) Failure to receive regular Pap test screening Long term use of oral contraceptives
Persistence of HPV infections
80% of HPV infections transient and cleared within 1-2 years
10% get persistent infection - persistence of high-risk HPV type is required for cancer development AND maintenance → <1% develop cancer
6 diseases caused by HPV
1) Common wart (verruca vulgaris)
2) Plantar wart (verruca plantaris)
3) Anogenital wart: (condyloma cumintaum)
4) Respiratory papillomatosis
5) Epidermodysplasia verruciformis
6) Squamous cell carcinoma
Common wart (verruca vulgaris)
caused by HPV ____ or ____
small, rough tumor, on hands/feet
HPV2, HPV7
Plantar wart (verruca plantaris)
caused by HPV ____, ____, or ________
on sole or toes of foot
HPV1, HPV2, HPV4
Anogenital wart: (condyloma cumintaum)
caused by HPV ____ or ____
sexually transmitted
HPV6 and HPV11
Respiratory papillomatosis
caused by HPV ____ or ____
warts on larynx or in respiratory tract
HPV6 and HPV11
Epidermodysplasia verruciformis
rare AR disease, increased susceptibility to HPV
Squamous cell carcinoma caused by HPV
5 types of HPV that can cause this?
Cervical cancer or head/neck cancer
HPV16, HPV18, HPV31, HPV33, HPV45
Cervical cancer is typically caused by _____ and arises where?
HPV
arise within transformation zone (squamocolumnar junction)
Especially associated with HPV 16 and 18
High risk HPV: (6)
HPV16, HPV18, HPV31, HPV33, HPV45, HPV58
These are covered by current vaccine
Low risk HPV: (2)
HPV6, HPV11
HPV oncoproteins
cancer regresses when E6 and E7 are blocked
E6 protein: binds and degrades p53
E7 protein: binds phosphorylated-RB → release E2F transcription factor → activate cell replication and cell cycle progression
HPV can integrate into host chromosome → uncontrollable expression of E6/E7
HPV Vaccine
want to vaccinate before sexually active
Gardasil: contains 6, 11, 16, and 18
Cervarix: contains 16 and 18
Gardasil-9: contains 6, 11, 16, 18, 31, 33, 45, 52, 58
*How vaccine is made: HPV L1 protein only, an empty virus → immune response without risk of infection
Screening and diagnosis of cervical cancer
HPV pap smear / HPV test → positive, then test cytology, if negative, test again in 3-5 years → positive cytology then do colposcopy
Cause of acute endocarditis
Staph aureus
Most common sites: mitral > aortic > tricuspid > pulmonic
Causes of subacute endocarditis (3)
Viridans strep, Strep bovis, Enterococci (faecalis)
What are predisposing factors to developing subacute endocarditis?
pre-existing cardiac lesion → turbulent, non-laminar blood flow, endothelial trauma, and fibrin deposition
Cause of prosthetic valve endocarditis
coagulase negative staph (S. Epidermidis)
Local complications of endocarditis?
effect integrity of heart valves → valvular insufficiency, CHF, myocardial and valve ring abscesses, pericarditis, conduction system disturbances
What are embolic complications of endocarditis? (7)
EMBOLI released from valve vegetation
1) Stroke or PE
2) Splinter hemorrhages
3) Petechiae, subconjunctival hemorrhages
4) Janeway lesions: nontender flat lesions on digits
5) Osler’s nodes: tender, purplish raised papules on digits
6) Roth Spots: retinal flame-like hemorrhagic
7) Septic emboli to kidneys
What are immune complex deposition complications of endocarditis? (3)
1) Glomerulonephritis
2) Osler’s nodes (small vessel vasculitis)
3) Roth spots
Presentation of Necrotizing Fasciitis (4)
1) Presents with signs of systemic toxicity (hypotension, tachycardia, fever, leukocytosis)
2) Poorly defined area of erythema + pain out of proportion to physical exam
- Very tender in areas that are not erythematous → suggest deep tissue involvement
- Get thrombosis of small vessels and destruction of superficial nerves
3) Spreads along facial planes
4) Later findings: skin breakdown + bullae + anaesthesia
Bugs with a type 3 secretion system? (5)
EHEC EPEC Shigella Salmonella (typhoidal, and non-typhoidal) Yersinia
