3/6: Legionella, Coxiella, Plague, Zoonotic Diseases Flashcards
Legionella Pneumophila: general
gram negative, aerobic, plemorphic bacilli, no capsule
Legionella Pneumophila are found ____
primarily waterbound
also found in soil
Legionella Pneumophila are ___ pathogens. Meaning they only infect ____
opportunistic pathogens
only infect smokers, immune-compromised hosts
T/F: Legionella pneumophila are facultative intracellular bacteria
TRUE
Legionella pneumophila have 4 virulence factors. What are they?
- PAMPS
- Type IV Secretion System
- Legionella-containing vacuole (LCV)
- Low metabolic state
T/F Legionella Pneumophila causes typical pneumonia
false
causes a-typical pneumonia
Describe the PAMP virulence factors of legionella pneumophila
pili/fimbriae, flagella, LPS
Describe the LPS of legionella pneumophila
LPS of legionella pneumophila is less toxic than other LPS of gran neg strains
What is legionella-containing vacuole (LCV)_
replication vacuole INSIDE of a macrophage
Why is the low metabolic state of legionella pneumophila a virulence factor?
creates a resistance to essentially any form of killing (heat, chlorination)
cells are embedded in biofilm
Infection of legionella pneumophila begins when ______
aerosolized droplets of contaminated water are breathed into lunchs
legionella begins to grow inside of alveolar macrophages in the lungs
Once legionella begins to grow inside of alveolar macrophages in lungs, this causes ____
inflammation
causing NECROTIZING MULTIFOCAL PNEUMONIA
What type of pneumonia does legionella pneumophila cause?
a-typical
necrotizing multifocal pneumonia
Describe LCV (legionella-containing vacuole) once legionella is inside the macrophage of a phagosome
LCV - legionella-containing vacuole
bacteria surrounds itself with a membrane bound vacuole that blocks the fusion of a lysosome to it’s resident phagosome
bacteria recruits ER proteins, ribosomes, mitochondria
Bacteria replicates inside of vacuole leading to cell lysis and inflammation due to DAMPS
Type IV secretion system aka ____
Icm/Dot
Describe Type IV secretion system (aka Icm/Dot)
secretes over 300 proteins into the host cell
Legionella pneumophila virulence requires intracellular replication. This activates ____ response
TH1 adaptive immune response
What recognizes legionella LPS?
TLRs on macrophages and dendritic cells
Legionellosis is linked to ____
large, complex manmade water systems in hotels, hospitals, nursing homes
What are the 2 forms of legionelllosis?
Legionnaires’ Disease
Pontiac fever
Which of the 2 forms of legionellosis is the severe form? Which is the milder form?
legionnaire’s disease = severe
pontiac fever = mild
Legionnaire’s Disease affects what target population?
middle age-elderly smokers or those with chronic diseases
What is the mortality rate of those with legionnaire’s disease?
How does this change in a health-care establishment?
15% mortality rate of legionnaire’s disease
Higher mortality in health-care establishments because of population in this setting (they’re sick…)
What are the symptoms of legionnaire’s disease?
myalgia/headache, rapidly rising fever, dry cough and chest pain, chills, vomitting, diarrhea, confusion delirium, hepatic dysfunction common
Diagnosis of legionnaire’s disease is via ___
patient history intake + DIRECT FLUORESCENT ANTIBODY mixed with cultured infected tissue
(this tissue has to be very high quality so this works 25% of time)
Or can use PCR or special media (buffered charcoal yeast extract)
T/F: Penecillin is the treatment for legionnaire’s disease
FALSE
treatment = fluoroquinoline, azithromycin, erythromycin
Prevention of legionnaire’s disease can be by minimizing _____
aerosols in public places from contaminated water
Prevention of legionnaire’s disease can be by minimizing aerosoles in public places from contaminated water.
Why is this complicated?
because once legionella is inside the water, it forms a biofilm and has a LOW METABOLIC STATE
= resistance to chlorine and heat killing.
hard to get rid of once it’s in the water
Pontiac fever is the milder version of ____
legionnaire’s disease
Pontiac fever causes ___ symptoms
flu-like
Both pontiac fever and legionnaire’s disease are caused by ____.
Only pontiac fever is caused also by _____
both - contaminated water droplets
only pontiac fever - contaminated soil
Define zoonotic infections
humans acquire infections by direct or indirect contact with animals
Coxiella Burnetti general
gram negative
small coccobacilli
T/F Coxiella Burnetti are facultative intracellular pathogens
FALSE
they are OBLIGATE intracellular pathogens
Because coxiella burnetti are obligate intracellular pathogens, this means that they prefer ____
macrophages and phagocytic cells
Coxiella burnetti can grow well in ___
placental tissue
What is the infection dose of coxiella burnetti?
LOW INFECTIOUS DOSE
ID50 = 1
Coxiella burnetti causes ____ in those who are around animals a lot
q-fever
Coxiella burnetti has 5 virulence factors. What are they?
- PAMPS (LPS)
- Type IV secretion system (lcm/Dot)
- Resistance to low pH/enzymes of phagolysosomes
- Coxiella containing vacuole (CCV)
- Biphasic life cycle
Describe the biphasic life cycle of coxiella burnetti
- small cell variant (SCV) = NOT metabolically active. infectious phase (survive standard disinfection)
–>
- large cell variant (LCV) = metabolically active, only acts once inside the cell
Coxiella burnetti is inhaled via ___
aerosole transmission
dust on the farm is stirred up and inhaled by farmer
Once in the lungs, coxiella burnetti binds to ____ (describe in detail)
phagocytic cells - alveolar macrophages (passively taken up through phagocytosis) and monocytes.
*both of these are in reticuloendothelial system
nonphagocytic cells - like epithelium and endothelium
Once inside the phagosome, coxiella burnetti forms their CCV (coxiella containing vacuole).
Describe this.
coxiella containing vacuole is formed once inside the phagosome
this ALLOWS LYSOSOME TO FUSE
The lowered pH in CCV stimualtes coxiella to expand the size of the vacuole.
Once the CCV is formed, what happens in terms of the biphasic life cycle of coxiella burnetti?
How long does this take
Inside the CCV vacuole, coxiella transitions from SCV (small cell variant) –> LCV (large cell variant) and REPLICATES
this takes about 6 days
Coxiella burnetti causes ___ (disease)
q-fever
What are the symptoms of q-fever
What are the symptoms of severe cases….
flu-like symptoms begin about 20 days
can have stomach pain, nausea, diarrhea, vomiting, LIVER ISSUES ARE COMMON
severe cases…
pneumonia and hepatitis can occur, chronic infections are rare and are associated with endocarditis
What is the treatment for q-fever
doxycycline for 2 weeks
Doxycycline is used to treat many ____ infections
obligate intracellular
Yersina Pestis general info
gram negative, pleomorphic bacillus
Yersina pestis caused ____ in the late 19th-early 20th century
black plague
Describe the epidemiology of the black plague
(YERSINA PESTIS)
rats entered city to find food.
high # of non-immune rats lead to bacteremia and high rat mortality rates
fleas fed on rates = infected with yersina pestis
bacteria multiplies inside fleas = blocks GI system = throw up into human bite wound
Transmission of yersina pestis (during black plagiue) was highest when ____
there was high rat population and high rates of rat mortality
(duh. think about it.)
What are the 2 diseases associated with yersina pestis?
- bubonic plague (w/ sylvatic plague and urban plague)
2. pneumonic plague
Describe bubonic plague transmission
(yersina pestis)
bacteria infects rats, causing BACTEREMIA and is transmitted to other rat fleas. has 2 cycles:
- SYLVATIC CYCLE: infected fleas leave rt and go to other rats to infect them. rarely transmits to humans
- URBAN CYCLE: when many infected rats/fleas are in close contact with humans. infected fleas bite humans.
Describe pneumonic plague transmission
(yersina pestis)
humans are infected with yersina pestis that develops into BACTEREMIA infecting LUNGS
this can spread from HUMAN TO HUMAN
Yersina pestis have many regulatory systems for their virulence factors. What does that mean?
Regulatory systems sense environment and turn on/off virulence factors
What are the 2 virulence factors of yersina pestis when in the flea gut?
- phospholipase D
2. coagulase and polysaccharide biofilm
Describe how phospholipase D is a virulence factor for yersina pestis
yersina pestis multiplies easily in the foregut of the flea due to low temperature that activates phospholipase D (virulence factor)
this resists anti-bacterial factors in the flea gut
Describe how coagulase and polysaccharide biofilm are virulence factors for yersina pestis
As yersina pestis sits in the flea gut, this starves the fleas, blocking the digestion of blood, causing vomitting of bacteria into wound of feed
When yersina pestis is transferred to humans, what happens to the temperatuer?
temperature in flea foregut = low
temperature in humans = high
When yersina pestis is transferred to humans, increased temperature creates regulatory systems to turn “on” 4 new virulence factors.
What are they?
- different LPS (not recognzied by TLR)
- antiphagocytic F1 capsule
- Pla (plasminogen activator allows spread to tissues)
- Yops (protein that destroys/disrupts host cell)
Once yersina pestis is inside human phagocytes, what happens?
Yops disrupt and destroy host cell
bacteria enter blood stream (bacteremia)
travels to lymph nodes where lyse host cells (multiply rapidly to produce BUBO)
Define bubo
What bacteria is it associated with?
hermorrhagic suppurative lymphadenitis
associated w/ yersina pestis
Bubonic plague symptoms present ___ after flea bite.
What are the symptoms?
(yersina pestis)
2-7 days after flea bite
fever, painful bubo in groin/axilla
50% = progress to BACTEREMIA without treatment and die
5% = develop into pneuonomic plague
Pneumonic plague symptoms present ___ after exposure.
What are the symptoms?
(yersina pestis)
2-3 days after exposure
fever, malaise, toght chest, later cough, sputum, trouble breathing, blue lips occur
Death after 2-3 days, NO SURVIVORS W/O TREATMENT
How do you diagnose patients with yersina pestis-associated diseases?
patient history + gran-stain aspirate of bubo or immunofluorescence techniques
What is the treatemnt of yersina pestis-associated diseases?
gentamycin or streptomycin
Of meningitis is present with yersina pestis-associated diseases, what is the treatment?
ciprofloxacin or chloramphenocol
Brucella abortus general info
gran negative
small coccobacilli
aerobic
non-motile
Brucella abortus have an unusual envelope made of ____
why is this beneficial
phosphatidylcholine
this makes them resemble eukaryotic cells (beneficial)
Describe the growth rate of brucella abortus
slow
Brucella abortus causes brucellosis.
Describe this.
chronic infection that persists for life in animals within their reproductive organs (male and female)
causes spontaneous abortions, sterility, descreased milk production in pregnant cattle, goats, hogs.
How is brucellosis spread to animals?
(brucella abortus)
spread via DIRECT contact with infected tissue or INGESTING contaminated feed
How do we systeamically control brucellosis in animals?
vaccination of animals
and euthanizing infected animals
Higher cases of brucellosis are found in ___
mexico or states close to mexico
Humans can become infected with brucellosis when ____
they consume unpasteurized dairy products
or if they work around animals (vets, lifestock owners, slaughter workers)
are infected via ingestion, inhalation, cuts in skin or mucous membranes
Why does brucella abortus grow in placental tissues of aniamls but not humans?
animals placenta have ERYTHRITOL present. huamns do not.
Brucella abortus is a ____ intracellular parasite
facultative intracellular parasite of epithelial cells and phagocytes
Why do TLRs not recognize brucella abortus?
because brucella abortus has a phosphatidylcholine envelope (making it look like a eukaryotic cell)
so TLRs cannot recognize this envelope
Brucella abortus multiples and forms ____ in liver, spleen, bone marrow, reticuloendothelial systems
granulomas
Brucall abortus must inhibit ____ to survive
must inhibit phagosome-lysosome fusion and apoptosis of host cell
T/F Brucella abortus uses type IV sercretion system
true
What are the 2 immune responses to brucella abortus?
How affective are they?
- antibodies are formed (not protective)
2. Th1 response is critical to control the disease by clearing brucella from macrophages
Brucellosis is also called ____
undulant fever
Brucellosis symptoms present ___ after infection.
What are the symptoms?
7-21 days after infection
headache, chills, fever, periodic drenching night sweats which can continue for weeks, months, or years.
because generic symtpoms - hard to tell if someone has this.
Only 25% of patients with brucellosis have ____
enlarged lymph nodes or enlargement of lymphatic organs like spleen/liver
Describe the diagnosis of brucellosis
isolation via biopsy
bc it’s slow growing this requires long incubation period
serological tests available
What is the treatment of brucellosis of humans
what is the recovery like
doxycycline + rifampin
could be 2-7 days before fever breaks
10% of patients will relapse within 3 months of taking antibiotics
no vaccine
Francisella Tularensis general info
gram negative, small coccobacilli, aerobic, requires CYSTEINE
non-motile
Fansicella Tularensis is a ___ intracellular parasite of macrophages
facultative
Francisella tularensis causes ____ (disease)
tularemia
Which bacteria is considered a tier 1 agent by the US government? why?
francisella tularensis
because of low ID, ease of spread, high virulence
What are the 2 virulence factors of fransciella tularensis?
- Lipid rich capsule
2. unusual LPS (isn’t recognized by TLR but does induce protective antibodies)
Francisella tularensis is spread by ____
ID =
contact with infected mammal or arthropod (these can be infected w/o symptoms)
Many routes of infection
Low ID (less than 100)
Infection of francisella tularensis can be via ___
minor abrasions, insect bites, inhalation
Why can francisella tularensis multiply so much?
Where does it multiply?
LPS is not recognized, so bacteria can multiply until they are detected by phagocytes
they will multiply in many cell types, especially alveolar epithelial cells and reticuloendothelial organs forming GRANULOMAS
A ____ often develops at the site of infection from francisella tularensis
ulcerated lesion
Once fracisella tularensis is ingested into the phagosome, it blocks ____ and escapes into ____
blocks fusion of lysosome to phagosome
escapes into HOST CYTOPLASM
Tularemia has an incubation period of ____
2-5 days
francisella tularensis
Tularemia has various symptoms. The type of disease depends on _____
All cases begin with ____
Most common form is ____ due to ____
(francisella tularensis)
type of disease depends on site of inoculation and extent of spread
all cases begin with acute onset of high fever
most common = ULCEROGLANDULAR FORM due to tick bite or handling infected animals (produces ulcer and swollen lymph notes)
How do we diagnose tularemia?
(francisella tularensis)
patient history is important bc symptoms so similar to other more common illnesses
hard to culture
SEROLOGIC TESTS are commonly used
What is the treatment for tularemia?
(fracisella tularensis)
gentamycin or streptomycin
high risk populations can receive a live attenuated vaccine
Pasturella multocida general info
Gram negative, small coccobacilli, facultative anaerobe
T/F Pastuerella multocida is susceptible to penicillin
true
surprising
unlike most other gram negative rods
Pasturella multocida is part of ____
normal flora of most domestic animals
What is the general pathogenesis of pasturella multocida?
most common cause is infected cat/dog bite
develops within 24 hours after bite/scratch
causes diffuse CELLULITIS with well-defined border
