Mycology

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MarkPR
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Mycology
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2014-04-13 15:58:00
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Mycology
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Mycology
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  1. Describe two physical characteristics of A. fumigatus conidia that influence our enviromental exposure
 to
 this
 fungus
 and 
innate 
phagocyte 
processing 
of 
the
 conidia. 

For
 each
 characteristic, 
if
 removed,
 does 
it
 alter 
the 
virulence 
in 
a 
murine 
model 
of 
IA?
    Rodlet layer (hydrophobic spore coat), less easily spread as aerosol, no less virulent in murine model

    Melanin (Structural pigment), less virulent in murine model, melanin inhibits lysosomal acidification.
  2. When 
does
 Cryptococcus 
form 
hyphae? 

Does 
this
 occur 
in 
the
 mammalian 
host? 

If
 not, 
describe 
the
 pathogenic
 morphotype 
of 
Cryptococcus.
    • Cryptococcus forms hyphae during sexual development under SPECIFIC
    • laboratory conditions on solid medium (and ostensibly in the environment as
    • well). It does NOT occur in mammalian hosts. When in the host it is in the
    • yeast form (may or may not be a spore)
  3. Give 
one
 reason 
why 
it
 is
 surprising 
that
 C. 
gattii 
is 
responsible 
for 
the 
‘outbreak’
 of
 cryptococcosis
 in 
the 
Pacific 
Northwest?
    • The infected individuals were otherwise healthy, and Cryptococcus
    • species are generally opportunistic.
  4. Some 
Aspergillus 
spp.
 are 
beneficial 
to 
humankind, 
please
 give 
2
 examples.
    A. niger, produces citric acid

    A. terrus, produces Lovastatin (cholesterol medication)
  5. List
 two 
fungal
 species 
we’ve 
discussed 
in
 class 
that
 are
 AIDS‐Indicator 
Disease‐causing
 organisms.
    P. marneffei (#3 AIDS-Indicator in SE Asia)

    C. neoformans (#1 AIDS-Indicator in SE Asia and high ranking in many other locations)
  6. Aspergillus
 fumigatus
is 
a
 (dimorphic/monomorphic) 
fungus 
that 
is
 capable 
of 
growing
 filamentously 
through 
tissues
 of 
patients 
with 
(healthy/suppressed) 
immune
systems.
    monomorphic, suppressed
  7. Aspergillus 
fumigatus 
is 
a(n) 
(ascomycete/basidiomycete) 
and
 Cryptococcus 
neoformans
 is
 a(n)

    (ascomycete/basidiomycete).
    ascomycete, basidiomycete
  8. The 
most
 common 
clinical
 presentation 
for 
C.
neoformans 
is 
__.

However,
 C.
gattii 
can 
manifest 
disease 
as a 
____ 

infection 
in 
immunocompetent
 individuals.
    pulmonary infection (pneumonia), CNS (disseminated)
  9. A.
fumigatus  
conidia 
contain 
immunomodulatory 
secondary 
metabolites 
that 
can 
interfere
 with 
mucocilliary 
clearance.
    True
  10. Azole 
resistant 
A.
fumigaatus 
 isolates 
can 
be 
a 
clinical 
problem.
    True
  11. Amphotericin 
B
 resistant
 A.
fumigatus 
isolates 
can 
be 
a 
clinical
 problem.
    False
  12. Amphotericin 
B 
is 
a 
nephrotoxin.
    True
  13. Cryptococcus 
is 
the 
only
 encapsulated
 yeast 
that
 causes 
disease 
in 
humans.
    True
  14. The 
main 
route 
of 
infection 
for
 C.
gattii 
is
 direct
 subcutaneous 
deposition.
    False
  15. Only
 the 
spore 
form
 of 
Cryptococcus 
causes 
disease 
in 
mice.
    True
  16. More 
HIV‐infected 
individuals 
in 
Sub‐Saharan
 Africa
 die 
from
 Cryptococcos
 than 
TB.
    True
  17. ‐Spores 
that 
are 
very 
tiny
 are
 better
 at:
 
           a)

Evading
 phagocytosis 
by
 alveolar 
macrophages
           
    b)

Entering
 the
 deepest 
recesses 
of 
the 
lung
 alveoli

    c)

Eliciting 
an
 allergic 
reaction

    
d)

Causing 
ocular
 infections
    B
  18. ‐Invasive 
aspergillosis
 (IA) 
is
 characterized 
by:

    
a)

Angioinvasion

    b)

High 
mortality
(≤90%)

    
c)

Nonspecific 
symptoms

    d)

Skin 
lesions 
of 
the 
hands 
and 
feet
    A
  19. Production 
of
 ___ 
by 
A.
fumigatus 
hyphae 
contributes 
to 
its 
ability 
to
 penetrate
 a 
variety
 of
 host 
tissues.

    a)

Proteases

    b)

Lipases

    c)

Spores

    d)

Antibodies
    A, B
  20. Cryptococcus 
is
 frequently 
found 
in/on:

    a)

Eucalyptus 
trees

    b)

Bird
 guano

    c)

Only 
soils 
of 
the
 American 
SW

    d)

None
 of
 the 
above
    A,B
  21. Compare
 and
 contrast 
the
 spores 
of 
Fusarium
 and 
Aspergillus.

 Be 
sure 
to 
include 
2
 similarities 
and 
2 
differences.
    • Aspergillus spores are small and round, while Fusarium spores are larger (in micro and
    • macro forms) and ovular. Also, Aspergillus spores are hydrophobic while
    • Fusarium spores are hydrophilic (making them ‘sticky’)

    Both have asexual spores, and both have spores that can become airborne for dispersal
  22. What 
is
 onychomycosis? 

Describe 
the 
symptoms.
    • Fungal Infection of the nail (toe or foot).
    • Nail becomes thick and discolored, it later becomes brittle and can begin to fall away. Skin around nail can become inflamed and sore, and there is a foul smell.
  23. While 
not a 
direct 
interaction 
of 
fungus 
with 
human 
tissue,
 contamination 
of 
foodstuffs

     with 
mycotoxins 
is
 an 
immense
 problem 
with
 severe 
consequences 
to 
human 
health.


    Describe 
a 
toxin 
discussed 
in
 lecture 
produced 
by 
Fusarium.
    • Deoxynivalenol (Vomitoxin) inhibits protein biosynthesis. It’s toxicity relies upon its
    • epoxide group. It can be a carcinogen in humans as well as cause apoptosis of
    • cells in the kidney, lungs and hepatocytes. In livestock is causes a refusal to
    • feed as well as a lack of weight gain.
  24. Give 
one 
reason 
why a 
biopsy 
to 
diagnose
 candidiasis
 could 
result 
in
 a 
false
 positive.
    Candida spp. are commensal as well as pathogenic, a biopsy cannot distinguish a colonizing and harmless candida from a harmful pathogenic candida
  25. Candida spp. are commensal as well as pathogenic, a biopsy cannot distinguish a colonizing and harmless candida from a harmful pathogenic candida
    • Adhesins:
    • Adhesins act as both a factor for efficient attachment and specificity of candida. They first recognize a suitable host (whether it be host cell ligands in living hosts or a suitable abiotic surface) and then facilitate the
    • attachment to the host so growth may begin

    • Dimorphism: In standard conditions candida are yeast like cells that (previously) were believed to be non-pathogenic. The ability to
    • shift to a hyphael form is required for pathogenesis as those incapable of the
    • shift cannot become the infective hyphael form

    • Secreted Enzymes:
    • SAPs are secreted aspartyl proteinases that have a broad spectrum of specify and can break down a wide spectrum of essential proteins (certains types of SAPs are required for different infection sites). Phospholipases break down phospholipids into their fatty acid components. All of these structure and
    • proteins play important roles in the human body and their destruction is harmful
  26. Define 
a 
biofilm
 
be 
sure 
to 
include 
5
 special 
characteristics.
    • A biofilm is a three dimensional microbial community made up of a network of adherent cells connected by channels. They are encapsulated by an extracellular polymeric
    • matrix made up of proteins and polysaccharides. Biofilms are never free
    • floating, rather they adhere to a surface using various adherent structures/adhesins and build up off the surface. They are associated with surfaces that might be medically relevant such as catheters or dentures.
    • Biofilms are much more resistance to treatment then their free floating
    • counterparts do partially  to the structures they create between the surface and the environment that can prevent treatments from reaching the cells along the surface. Biofilms are also resistant to host defense mechanisms and even a healthy host that could fight off a non-film infection might be unable to clear a biofilm infection.
  27. What 
erroneous 
conclusion
 would
 have 
been
 drawn 
if 
the
 albino 
A.
fumigatus
 strain
 were

    only
 studied 
in
 G.
mellonella?
    • That they were the more virulent strain (compared to non-melanin deficient strains). This is false, as further tests in mice revealed that melanin is actually an important
    • virulence factor in A. fumigatus
  28. List
 3
 strengths 
and 
3
 weaknesses 
of
 using
 invertebrates
 as 
hosts
 to
 study 
mycoses.
    • Strengths:
    • Low Cost (invertebrates are easy togrow/care for and cheap to buy)
    • Few ethical dilemmas (No one really cares about bugs)
    • Complex innate immune systems (lack of adaptive means that inverts have robust innate)

    • Weakness:
    • Not mammalian (not always best model for how a fungal infection would behave in humans)
    • Lack adaptive immunity (action of adaptive in fungal infection cannot be determined)
    • Careful interpretation (data collected must be taken with a grain of salt)
  29. Candida 
glabrata 
is 
the 
(second/third) 
most
 causative
 agent 
of 
disease
 after 
C.
albicans 
in

    the 
Candida
 genus. 

Also, 
it 
is
 generally 
(more/less) 
susceptible 
to 
antifungals
    Second, less
  30. F.
oxysporum
 has 
the
 broadest 
host 
range
 compared 
to
 other 
species
 within 
the
 genus.
    True
  31. Fusarium 
macroconidia 
are 
mononucleate
    False
  32. Candida 
is 
the 
most 
common 
fungal
 pathogen
 of
 humans.
    True
  33. Candida 
is
 NOT 
a 
commensal 
of 
the 
human
 microbiome.
    False
  34. Incidence 
of
 candidemia 
is 
declining.
    False
  35. Treatment 
is 
irrelevant 
for
 urinary 
candidiasis
    True for asymp, false for symp
  36. Oral
 candidiasis 
(white
plaques) 
is
 often
 a 
hallmark 
disease 
in 
individuals
 with HIV/AIDS.
    True
  37. Biofilms 
only 
form 
on 
a biotic
 surfaces.
    False
  38. Candida 
biofilms
 are 
up
 to 
1000x 
more
 drug 
resistant 
vs 
free‐floating
 cells.
    True
  39. If 
you
 were 
a 
funga l
pathogen, 
you’d like 
to 
hang 
out
 in 
a 
biofilm
    True
  40. Fusarium 
is 
a
 diverse
 genus 
primarily 
known 
for 
being:

    a.

Opportunistic
 human 
pathogens

    b.

Primary
 human 
pathogens

    c.

Primary 
plant 
pathogens

    d.

Delicious
    C
  41. The 
following 
diseases
 can 
be 
caused 
by 
Fusarium 
in immunocompetent 
individuals:

    a.

keratitis

    b.

onychomycosis

    c.

disseminated/invasive

    d.

sinusitis


    e.

pneumonia
    A,B
  42. The 
following 
diseases 
can
 be 
caused 
by 
Fusarium
 in
 immunocompromised 
individuals:

    a.

keratitis

    b.

onychomycosis

    c.

disseminated/invasive

    d.

sinusitis


    e.

pneumonia
    C,D,E
  43. Iatrogenic
 risk 
factors 
for 
disseminated
 candidiasis 
include:

    a.

burns

    b.

central
venous
catheter

    c.

malignancy

    d.

antibiotics

    e.

diabetes

    f.

surgery
    D,F
  44. If you
 suspect
 a
 patient
 of
 yours
 has 
a
 Candida 
biofilm 
on
 a
 vascular
 catheter
 and
 no
 sign 
of
 disseminated
 candidiasis, 
the
 single 
best
 course 
of
 action 
is 
to:
   
    a.

treat with 
intravenous
 AmpB, then
 oral
 azoles 
for 
6 
weeks

    b.

follow‐up 
after 
1 
week

    c.

check 
for 
fever

    d.

remove 
the 
catheter
    D
  45. The 
following 
are 
critical 
for 
Candida 
biofilm
 formation:

    a.

adhesins

    b.

farnesol

    c.

polymicrobial 
interactions

    d.

ECM
 deposition
    A, C, D
  46. The 
following 
host
 components 
have 
been
 experimentally 
shown
 to
 be
 major
 components
 of 
Candida
 biofilms:

    a.

calcofluor

    b.

fibrinogen

    c.

fibronectin

    d.

neutrophils
    B,C
  47. The 
following
 are 
lacking 
in
 an 
in 
vitro system 
compared 
to
 whole‐animal:

    a.

cytokine
 signaling

    b.

disease 
progression 
(ex,
lung 
to 
liver)

    c.

microenvironment

    d.

antigen
 presentation
    B,C,D
  48. The 
following
 model(s) 
would
 NOT
 be appropriate 
for
 studying 
the
morphogenic 
switch
 of
 a 
thermally 
dimorphic 
fungus:

    a.

G.
 mellonella

    c.

M.
 musculus

    d.

in
 vitro
 mammalian 
cell
 culture

    e.

D. 
rerio
    E
  49. The 
most
 direct 
method
 for
 addressing 
whether 
or
 not
 a 
C.
neoformans 
mutant 
is 
deficient 
for 
growth 
in
 the
 CNS 
would 
be
 to 
use 
the
 following 
infection
 route 
in 
the
 mouse/rabbit:

    a.

tail 
vein 
injection

    b.

intranasal

    c.

intratrachael

    d.

intrathecal

    e.

subcutaneous
    D
  50. Define
 superficial, 
cutaneous,
 and 
subcutaneous 
mycoses. 

Include 
in
 your
 answer
 location/symptoms
 of
 each, 
whether 
an 
immune 
response 
is
 evoked, 
and 
list
 one
 potential
 treatment
 option 
for
 each.
    • Super: Effect outermost layers of skin and hair (symptoms are cosmetic, i.e. visible growths, discoloring)
    •                   -Salicylic acid

    • Cutan: Effect epidermal, can include invasive hair/nail (lesions, disfigurement of nails)
    •                    -azoles

    • Subcu: Effect dermal layer and lower (subcu tissues, muscle, fascia) (destruction of tissue/fascia, nodule formation)
    •                     -Surgical removal of infected tissue
  51. List 
two 
predisposing
 conditions 
for 
susceptibility 
to 
subcutaneous 
mycoses 
and 
the
 two
 common 
infection 
routes 
covered 
in
 class.
    • 1.Disruption of skin barrier (generally via trauma)
    • 2.Underlying systemic condition reducing host defenses (AIDS,
    • immunosuppressives)


    • 1.Inhalation
    • 2.Traumatic inoculation
  52. Define
 siderophore.
    Siderophores are iron chelating compounds secreted by microorganisms. They pull iron out of the surround environment for the micro’s use. This can cause harmful effects in host organisms
  53. While 
it
 may 
seem
 obvious 
that 
nutrient
 acquisition 
is 
a 
virulence
 determinant,
 the 
host
 environment 
is 
exceptionally 
nutrient 
restrictive. 

Describe 
a
 fungal 
virulence
 determinant
 that 
is 
involved 
in 
the 
acquisition 
of
 carbon. 

What 
central
 metabolic 
pathway 
does 
this
 ‘bypass’?
    • Use of the glyoxylate cycle. The glyoxylate cycle takes isocitrate and converts it to malate, bypassing a large portion of the TCA cycle seen in animals. This is beneficial for the fungus as it allows them to utilize lipids
    • and acetate in place of carbohydrates to grow their cellular structures
  54. List 
3 
fungal 
cell
 drug 
targets
 and
 a
 single 
representative 
drug 
or 
drug 
class 
for 
each 
target.
    • Cell wall (glucans): Echinocandins
    • (inhibit (1,3)-b-D-glucan synthase, which 
    • forms glucan polymers in the  cell wall)

    DNA synthesis: Flucytocine (is converted in cell to other chemicals capable of stopping DNA synthesis and protein synthesis

    Plasma Membrane (ergosterol): Amphotericin B (creates pores in ergosterol allowing flood of ions)
  55. Microbiology
 lab 
results 
come
 back
 regarding
 one
 of
 your
 patients
 and 
they
 test 
positive

    for
 yeast 
in 
the
 blood. 

Based
 on 
your 
experiences, 
you 
suspect 
one
 of
 the 
top 
3 
most
 causative 
Candida
 species
 (C.
albicans,
C.
glabrata,
C.
tropicalis) 
but
 you
 don’t
 know
 which
 species 
it is 
specifically.

 What
 antifungal
 drug 
would
 you
 order 
initially?

 Ooops!
–
test
 results
 come 
back
 a 
few 
days
 later 
and
 you’re 
surprised 
to
 find
 it
 is 
C.
parapsilosis,
 what
 drug 
would 
you
 switch 
to?

 Why?
    • Initially I would order echinocandins as most all anti-fungals work on albicans and tropicalis and echinocandins are exceptional against glabrata. When I learn of the actual
    • species I would switch to triazole as echinocandins are not effective against
    • parapsilosis
  56. Malassezia 
are (lipophilic/hydrophilic)
 species 
afflicting
 >50%
 of 
humans
 causing
 dandruff
 and 
is 
closely 
related 
to 
the 
plant
 pathogen
 (Ustilago/Fusarium).
    Lipophilic, Ustilago
  57. In
contrast 
to
 Aspergillus,
 when
 viewed
 histologically 
in
 a 
tissue
 section
 fungi
 that
 cause
 subcutaneous 
mycoses 
have
 (broad/narrow)
 (septate/aseptate)
 hyphae.
    Broad, aseptate
  58. Histamine 
is released 
from
 __________
 cell
granules .

Histamine
 (increases/decreases)
 vascular 
permeability 
and 
causes 
smooth
 muscle 
(contraction/relaxation). 

________
is
 a
 common
 antihistamine
 drug.
    • mast, increases, contraction,
    • Benadryl
  59. Echinocandins
 are
 (static/cidal)
 for
most 
Candida
 spp. 
and
 (static/cidal) 
for
 Aspergillus.
    Cidal,static
  60. Dermatophytes 
can 
be 
characterized 
by 
the 
features 
of
 their 
macro‐
and
 microconidia
    True
  61. Following 
a 
traumatic 
introduction 
of 
environmental 
material
 into 
the
 skin,
 a
 patient 
develops 
small,
 hard,
 painless
 subcutaneous 
nodules 
along 
the
 lymphatic
 system
 route.


    A 
likely 
culprit 
fungus
 would
 be
 Sporothrix.
    True
  62. Rhizopus 
can 
make 
your
 bread
 fuzzy.
    True
  63. Microbial 
adherence 
to 
a 
eukaryotic 
cell 
requires 
the 
complementary 
chemical
    interaction 
between 
the
 host 
cell
 receptor 
and 
a
 pathogen
 surface 
ligand
    True
  64. Only 
fungi 
produce 
siderophores
    False
  65. Leukotrienes 
are 
important 
mediators
 of
 the 
asthmatic 
response
    True
  66. Amphotericin 
B
 binds 
to
 fungal
 membrane 
sterols
 and 
alters 
permeability 
to
 potassium 
and
 magnesium
    True
  67. Amphotericin 
B 
is 
NOT 
a
 good
 choice 
for 
treating 
infections 
caused
 by 
the
 endemic
        fungi.
    False
  68. Therapeutic
 drug 
monitoring
 can
 be 
an 
important
 step 
in
 the 
efficacy
 and 
safety
 of
 antifungal
 drug 
treatment
    True
  69. Mincle
 is
 a
 C‐type 
lectin 
receptor 
that
 recognizes:


    
         a.

α‐mannose


    
         b.

β‐galactosidase


    
         c.

β‐(1,3)‐glucan


    
         d.

β‐(1,6)‐glucan


    
         e.

None
of
the
above
    A

  70. Mincle 
is 
a
 C‐type 
lectin 
receptor
 that 
appears 
to 
be
 specific 
for 
recognizing
______
species:

             a.

Trichosporon

             b.

Exophiala

             c.

Piedraia
             d.

Malassezia

    Mincle
is
a
C‐tye
lectin
receptor
that
appears
to
be
specific
for
recognizing
______
species:

    D
  71. Keratinophilic 
fungi
 can 
infect
 the:


    
         a.

head


    
         b.

nails
of
the
hands
and
feet


    
         c.

bearded
areas


    
         d.

feet


    
         e.

none
of
the
above
    A,B,C,D
  72. The 
following
 are 
essential
 considerations 
when 
prescribing 
an 
antifungal 
drug:


    
         a.

species
of
fungus
involved


    
         b.

localisation
of
infection


    
         c.

distribution
properties
of
the
drug


    
         d.

elimination/metabolism
of
the
drug


    
         e.

none
of
the
above
    A,B,C,D

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