Mycology Exam 1 Cocccidiodomycosis

Front 1

How is coccidioides classified

Back 1

haploid ascomycete

Front 2

Name two species of coccidioides and describe their relationship in terms of distribution, mophology, and clincal presentation

Back 2

C. immitis-San Joaquin Valley of CA
C. posadasii- SW USA, Mexico, Central America, South America
identical morpology and clinical presentation

Front 3

Coccidioides is a thermal dimorph. Describe its two states

Back 3

25C saprobic phase- mycelia/mold, multinucleate arthorconidia alternating with empty cells
37C parasitic phase- spherules, uninucleate endospores

Front 4

What role does CO2 and 17-B estradiol play in Coccidiodes phase switching?

Back 4

CO2 and 17B estradiol favor the spherules endospore form (explains higher incidence in pregnant women)

Front 5

Describe the ecological niche of Coccidioides

Back 5

Lower Sonoran life zone
arid climate, litte rain, alkaline soil, hot summers, winters with few freezes

Front 6

What is the infectious form of Coccidioides

Back 6

arthroconidia

Front 7

Describe stage I of Cocci spherulation

Back 7

-less than 24 hrs
-arthroconidia enlarge and become uninucleate

Front 8

Describe stage II of Cocci spherulation

Back 8

24-28hrs
-arthorconidia become spherules
-Spherules undergo isotropic growth
-Synchronous nulear division produces multinucleate spherule

Front 9

Describe Stage III of Cocci spherulation

Back 9

-72-96 hrs
-nuclear division ceases
-segementation to form uninucleate endospores
-mature sperule

Front 10

Describe stage IV of Cocci spherulation

Back 10

-spherule rupture
-200-300 endospores within each spherule capable of developing into a spherule

Front 11

What is the role of the BGL2 gene in Cocci pathogenesis

Back 11

-encodes B glucosidase
-expressed only in parasitic phase with highest expression during isotropic growth
-Thought to cleave B 1-3 glucan polymers to allow for cell wall expansion during isotropic growth

Front 12

What would be the consequence to Cocci pathogenesis of a BGL2 deletion

Back 12

-slowed spherule development
-attenuated virulence

Front 13

List the 4 major virulence factors of Cocci

Back 13

1. Spherule Outer Wall (ECM)
2. Spherule Outer Wall Glycoprotein (SOWgp)
3. Extracellular Proteinases
4. Urease

Front 14

Describe the role of Cocci spherule outer wall matrix in pathogenesis

Back 14

-composed of lipids and proteins
-imapirs direct PMN contact with spherules

Front 15

Describe the role of Cocci SOWgp in pathogenesis

Back 15

-localized to spherule cell surface
-functions as an adhesion (laminin, fibronectin, collagen)
-expressed during isotropic growth

Front 16

What would the consequnce of a SOWgp deletion be to Cocci pathogenesis

Back 16

-decreased spherule binding to host ECM protiens
-attenuated virulence, TH1 (what you want) rather than TH2 (ineffective) response is illicited

Front 17

Describe the role of MEP1 Metalloproteinase in Cocci pathogenesis

Back 17

-Peak expression during endosporulation, minimal during isotropic growth
-Functions as an immune evasin by digesting SOWgp on endospores

Front 18

What would the consequnce of a MEP1 deletion be to Cocci virulence

Back 18

-MEP1 digests spherule outer wall glycoprotein
-increase in SOWgp on the cell surface of endospores
-increased suceptibility to phagocytosis
Cocci must establish a balance between expression of SOWgp to be able to bind to ECM but digestion of it to avoid the immune system

Front 19

Describe the role of urease in Cocci pathogenesis

Back 19

-Encoded by URE gene which is expressed in both mycelia and sperules
-released following spherule rupture
-enhances virulence

Front 20

Describe the role and efficacy of neutrophils in host response to Cocci infection

Back 20

-first cell to reach site of infx, arothroconidia and endospore stimulate chemotaxis
-phagocytosis of arthroconidia and endospores but <20% killed
-NO phagocytosis of spherules because of size and SOW complex

Front 21

Describe the role and efficacy of non-T cell stimulated macrophages/ monocytes in host response to Cocci infection

Back 21

-phagocytosis of arthroconidia and endospores (NOT spherules) but only 1-25% killed
-anthroconidia and endospores that survive become mature spherules
-there is inhibtion of phagolysosome fusion

Front 22

Describe the role and efficacy of natural killer cells in the host immune response to Cocci infection

Back 22

kill arthorconidia and young spherules

Front 23

What is the only innate immune response element that can kill Cocci spherules

Back 23

natural killer cells but even then it's only the young ones. Neuts and monos/ naieve macs cannot!

Front 24

Describe the role and efficacy of T-lymphocytes in host response to Cocci infection

Back 24

-crucial for control and defense
-those with strong Type IV HS Rxn have Asx or subclinical Infx
-those with weak Type IV HS have chronic or disseminated infection

Front 25

What is the main/ crucial function of T-lymphocytes in host response to Cocci infection

Back 25

The T-lymphs of the adaptive immune response stimulate macrophages with IFN-g which helps the macs kill arthorconidia and endospores

Front 26

T/F Cocci spherules can be phagocytosed

Back 26

false, their size and SOW prevent phagocytosis by either neuts or macs

Front 27

When is the peak incidence of Cocci infection

Back 27

late summer and early fall due to dry soil, airborne arthroconidia in dust

Front 28

T/F most Cocci infections are problematic

Back 28

False 50-67% are asymptomatic

Front 29

What two classificaitons of disease are cause by Cocci

Back 29

pulmonary, extrapulmonary

Front 30

Describe the pulmonary presenation of Cocci

Back 30

-Pneumonia
-Fever, cough, chest pain, fatigue, dyspnea, headahce, rash, eosinophilia
-chest imaging with inflitrates/ consolidation, Hilar LAD, pleural effusion, pumonary nodule, cavity, fibrovacitary

Front 31

Describe the Extrapulmonary/ disseminatied disease cause by Cocci
Risk factors?

Back 31

-any organ but skin is most common follwed by CNS and bone, less common include eyes, larynx, heart (endocarditis), genitounirnary (prostate), joint (septic arthritis)
risk factors- non-white ethnicity, male or pregnant female, extreme of age, immunocompromised

Front 32

How can Cocci be Dx'ed

Back 32

-sputum or tissue staining with KOH, calcofluor, H&E, Silver, PAS
-NOT gram stain
-culture w/ LPCB prep
-confirm with DNA probe test
-serological test (tube precipitin TP IgM test)
-Complement fixation (CF IgG test), antigen is chitinase, look for improved titer

Front 33

Describe the Tx for Cocci

Back 33

Azoles
Amphotericin

Front 34

Why must a the lab always be warned if a sample is suspected to contain Cocci

Back 34

-Considered a select agent with bioterrism potential but this is a questionable classification