Microbiology - RC Flashcards
(56 cards)
1
Q
What are the features of an “ideal” antimicrobial?
A
L4
- selective toxicity against microbial target
- minimal toxicity to the host
- no adverse drug interactions
- long plasma half-life
- good tissue distribution
- cidal activity
- low binding to plasma proteins
- oral and parenteral preparations
2
Q
What are the pathogenicity factors of C. albicans?
A
L7
- adhesion
- dimorphism
- secretion hydrolytic enzymes
- interaction with immune system
- toxin production: candidalysin
3
Q
How is adhesion a pathogenicity factor in C. albicans?
A
L7
adhesion allows the cell to overcome the clearance function of the innate immune system
4
Q
How is dimorphism a pathogenic factor in C. albicans?
A
L7
= yeast and hyphae growth
hyphae can penetrate tissue + burst out of macrophages
(strains that are defective in mycelial formation are less virulent)
5
Q
What are the secreted hydrolytic enzymes of C. albicans and how are they pathogenic factors?
A
L7
- secreted aspartic proteinases: degrade sIgA, promote adhesion + aid tissue penetration/destruction
- phospholipase: degrades phospholipids = destroy cell membranes + aid tissue penetration
6
Q
How is interaction with immune system a pathogenic factor in C. albicans?
A
L7
- grow out of phagocytes after being engulfed
- secreted proteinases may degrade antibodies
- hyphae secrete a substance that inhibits polymorphonuclear leukcyte (neutrophil, basophil etc.) degranulation (release of cytotoxic molecules + prevents phagocytosis
- supress T-cell proliferation
- bind C3b + C3d complement proteins which masks cell from phagocytes
7
Q
How is candidalysin toxin production a pathogenic factor in C. albicans?
A
L7
- permeabilises the host cell membrane
8
Q
What are the predisposing factors of developing oral candidosis?
A
L8
- prosthesis
- low saliva flow
- antibiotics
- malignancies + cytotoxic therapy
- corticosteroids
9
Q
Why does prosthesis predispose for oral candidosis?
A
L8
- tissue trauma breaches barrier component of innate immune system
- compromised saliva flushing function
10
Q
Why does low saliva flow contribute to developing oral candidosis?
A
L8
- reduced flushing action of saliva
- innate immune system
11
Q
Why are antibiotics a predisposing factor for oral candidosis?
A
L8
- reduce microbial competition by inhibiting bacteria
- causes increased number of candidda
12
Q
Why are malgnancies and cytotoxic therapy predisposing factors for oral candidosis?
A
L8
- impair phagocytosis by neutrophils + macrophages
- affects cell mediated and acquired immunity
13
Q
Why are corticosteroids a predisposing factor in oral candidosis?
A
L8
- immunosuppressive
- used by asthmatics + absorbed into oral mucosa which increased the chance of fungal infections
14
Q
What are the types of oral candidosis?
A
L8
- pseudomembranous candidosis (oral thrush)
- acute and chronic erythematous candidosis
- plaque-like/nodular candidosis
- angular cheilitis
15
Q
Who is likely to get oral thrush (pseudomembranous candidosis)?
A
L8
- infants
- elderly
- immunocompromised (HIV + AIDS patients)
- asthmatics using steroid inhalers
16
Q
What is the clinical presentation of oral thrush (pseudomembranous candidosis)?
A
L8
- creamy-white plaques
- can be removed with a swab
- bleeding mucosa underneath plaques
17
Q
What forms the pseudomembranes seen in oral thrush (pseudomembranous candidosis)?
A
L8
desquamated epithelial cells + Candida hyphae
18
Q
When does acute erythematous candidosis occur?
A
L8
- often follows course of broad spectrium antibiotic
- occurs due to loss of competition
- thus also called “antibiotic sore tongue” and “acute atrophic candidosis”
19
Q
What is the clinical presentation of acute erythematous candidosis?
A
L8
- reddeninh of tissue
- inflammation
- painful
- papillae not evident due to inflammation of tongue: looks smooth
20
Q
What is the factor that leads to chronic erythematous candidosis?
A
L8
- affects denture wearers
- is the most common form of candidosis
- also called “denture-induced candidosis” and “denture sore mouth”
21
Q
What is the clinical presentation of chronic erythematous candidosis?
A
L8
- inflamed palatal mucosa
22
Q
What are the other names for plaque-like/nodular candidosis?
A
L8
- chronic hyperplastic candidosis
- candidal leukoplakia
23
Q
What is the clinical presentation of plaque-like/nodular candidosis?
A
L8
- irregular white plaques that cannot be removed by scraping
- liable to undergo malignant transformation
24
Q
What can angular cheilitis be caused by?
A
L8
- can be caused by bacteria such as staphylococci
- can also be caused by Candida
25
What is the clinical presentation of angular cheilitis?
L8
- inflammation
- ulceration
- crusting
26
What are some anti-fungal drug types and their sites of action?
```
L8
5-fluorocytosine: DNA RNA synthesis
polyenes: membrane integrity
azoles: sterol synthesis
echinocandins: wall synthesis
```
27
What is the mode of action of 5-fluorocytosine?
L8
- fungicidal
- administered as a prodrug which is metabolised in fungal cell to active metabolite
- metabolite interacts with RNA and DNA synthesis = abnormal RNA + proteins
28
What examples of polyene antifungal drug?
L8
| - nystatin + amphotericin B
29
What is the mechanism of action for nystatin and amphotericin B?
L8
- fungicidal
- insert and aggregate with ergosterol in cell membrane
- form channel with pore
- cause H+ and K+ ion leakage
- cell death
30
What is an example of a azole antifungal drug?
L8
| - fluconazole
31
What is the mode of action for fluconazole?
L8
- fungistatic
- inhibits an enzyme in the pathway to ergosterol production
- results in loss of membrane integrity
- causes cell lysis
32
Why is fluconazole not toxic to humans?
L8
- ergosterol is equivalent to cholesterol found in mammals
- different production pathway so able to target this difference
33
What preparations are available for nystatin + amphotericin B, and fluconazole?
```
L8
nystatin + amphotericin B:
- topical: suspension, pastilles, lozenges, and ointment
fluconazole:
- systemic: capsules
```
34
What are the possible drug resistance mechanisms for Candida?
L8
1. alteration in metabolic pathway (5-FC + polyenes)
2. over-expression of drug target (azoles)
3. mutation in drug target (azoles)
4. over-expression of drug pumps (azoles)
35
How does drug resistance affect 5-FC (antifungal)?
L8
- mutations in UMP pyrophosphorylase enzyme
- partially resistance strains can acquire full resistance
36
What is the mechanism of polyene drug resistance in fungi?
L8
- changes in the sterol composition of the plasma membrane
- if no sterols present, then polyenes cannot interact to form pores
37
What is the mechanism of azole antifungal drug resistance?
```
L8
C. albicans can acquire azole drug resistance by:
- over-expression of drug target
- mutation of drug target
- energy-dependent drug efflux
```
38
Resistance to which antifungal drug is a problem to some patients?
L8
- azole resistance
- problem to AIDS patients with oropharyngeal candidosis
39
What are the reasons for the recurrence of fungal infections?
L8
- patients have another endogenous source of Candida for re-infection
- impaired immune system
- used a fungistatic drug
40
What is an example of viral latency?
L5
e. g. Herpes Simplex Virus (HSV)
- primary herpetic gingivostomatitis
- secondary herpes labialis (cold sore)
e. g. Varicella Zoster Virus (VZV)
- primary chicken pox
- secondary shingles
41
Describe the latency of HSV?
L5
- virus remains latent in sensory neurons in trigeminal ganglion
- reactivation: virus migrates down peripheral nerve
- causes lesions on mucocutaneous junction of the lip
42
What are the stages involved in virus replication?
L5
- adsorption
- penetration
- nucleic acid replication
- viral assembly and release
43
How does viral adsorption occurs?
L5
| - specific interaction between viral protein and host receptor
44
How does the viral penetration stage occur?
L5
- translocation (diffusion)
- endocytosis
- fusion of membranes
45
What occurs during the viral nucleic acid replication stage?
L5
- ssDNA: replicated to make complementary template which is used to make more copies
- dsDNA: replicated
- ssRNA: viral transcriptase to form complement (-ve or +ve sense) then again to form copy
46
What is a retrovirus?
L5
| - a ssRNA virus with a DNA intermediate
47
What is the replication cycle of retroviruses?
L5
- receptor binding + entry
- nucleoprotein complex
- reverse transcription = DNA
- DNA integration into host genome = provirus (viral latency)
- transcription = mRNA + pre-genome RNA
- mRNA translation = proteins
- proteins + pre-genome RNA = virus
48
What is involved during the viral assembly and release stage?
L5
- intracellular assembly and maturation = requires cell lysis for release
- enveloped virus: viral membrane proteins into cell membrane, capsid assembles intracellularly + associates with membrane proteins = virus buds from cell (e.g. HIV)
- nucleocapsid assembly occurs in nucleus (e.g. herpes)
49
What kind of virus is HIV?
L6
| - enveloped RNA retrovirus
50
What is the time course of HIV disease?
L6
- immune system detects the HIV virus and starts producing anti-HIV antibodies
- HIV affects white blood cells = decrease CD4 WBC count
- antibodies initially effect so cause a decrease in the amount of virus
- WBC are destroyed so cannot produce antibody anymore
- amount of virus increases
= immunodeficient
51
What are some anti-viral drugs?
L6
- acyclovir: HSV + VZV
- abacavir: HIV
- lamivudine: HIV
- ritonavir: HIV
52
What is the mechanism of action for acyclovir antiviral?
L6
- prodrug
- activated by phosphorylation by viral thymidine kinase
- potent inhibitor of viral DNA polymerase
53
What is the mechanism of action for abacavir + lamivudine antivirals?
L6
- nucleoside analogues
- inhibit retroviral reverse transcriptase
54
What is the mechanism of action for Ritonavir?
L6
- proteinase inhibitor
- aspartic proteinase required by HIV to cleave viral protein precursors
55
What resistance problems is there in antiviral drugs?
L6
- influenza significantly resistant to Amantadine
- HIV resistance to reverse transcriptase and proteinase inhibitors
56
What are the components of the innate immune system?
```
L10
- physical barriers: skin
- flushing action: saliva
- biological components: enzymes, phagocytosis, complement, inflammation,
nutrient privation
- microbial competition
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