Microbiology and parasitology Flashcards
what is the definition of microbial resistance?
decreased susceptibility of a fungal strain to an antifungal agent
why can microbial resistance occur?
intrinsic resistance or acquired resistance
what is the definition of clinical resistance?
therapeutic failure; a patient responds inadequately to an antifungal drug following administration of a standard dose
what is the mode of action of polyenes?
bind to ergosterol and form aqueous pores in the plasma membrane
name the 3 mechanisms of acquired resistance for polyene
- reduced amounts of ergosterol in cell membrane
- alteration of fungal cell membrane
- alteration of the fungal cell wall
what is the mode of action of azoles?
inhibit the biosynthesis of ergosterol
name the 5 mechanisms of azole resistance
- target is changed; reduced drug-target interaction
- increase in target copy number
- reduction of intracellular drug concentrations mediated via drug efflux transporters and reduced uptake
- modification of other ergosterol biosynthesis pathway elements
- biofilms and persistor cells
what is the mode of action of echinocandins?
inhibit the synthesis of B-glucan in fungal cell wall
name the 4 fungal drivers of resistance
- stress pathways
- generate tolerate cells
- mutations rise
- stable resistant isolates
name the 3 mechanisms of echinocandin resistance
- target is changed
- increase in target copy number
- biofilms and persistor cells
what is the difference between intrinsic and acquired resistance?
intrinsic resistance is natural resistance to anti-fungal drugs without any previous exposure and acquired resistance is resistance acquired through genetic mutation and passage of these resistant genes after exposure to drug
name the 3 types of Staphylococcus aureus carriers and describe them
- non carriers; resistant to colonization of S. aureus
- intermittent carriers; colonization with unique S. aureus genotype
- persistent carriers; colonization with one unique strain and resistant to colonization with different strain of S. aureus
which type of S. aureus carriers are at high risk for endogenous S. aureus infections?
persistent carriers
which microbial factor is involved in the nassal carriage of S. aureus?
staphylococcal protein A (SpA) is positively correlated with carriage duration
name the 4 characteristics of a pneumococcal co-infection with influenza virus
- epithelial damage
- decreased mucociliary velocity
- reduced CCL2 expression
- reduced macrophage functionality
how does the pneumococcal capsule contribute to disease?
capsule virulence factor is resistant against phagocytosis
what is competence in S. pneumoniae?
- horizontal gene transfer; transformation
- competence is induced by environmental signals (high cell density, stress)
- competence leads to killing neighboring cells
- competence stimulating peptide (CSP) secreted by competent cells
which proteins are essential for niche adaptation?
ATP binding cassette (ABC) transporters for nutrient transport
what is the function of pneumolysin?
toxin that form pores to induce inflammation for faster clearance and increased transmission
name the 3 prominences of S. pneumoniae as a cause of disease
- high carriage rates
- genetic adaptibility
- ability to shift from commensal to a pathogenic interaction with its host
name the 2 adaptations that is needed for niche adaptation
- metabolic adaptation; maintenance of metal levels, different carbon sources
- immunological adaptation; from non-sterile to sterile site
name the 3 limitations of current pneumococcal vaccines
- protection against a limited number of serotypes
- pneumococcal vaccines are designed based on prevalence in US and Europe
- expensive and complex from a development and manufacturing perspective
name the 5 requirements for an improved pneumococcal vaccine
- broadly protective
- affordable
- target groups: infants and elderly
- focus on reduction of carriage
- potential novel vaccine antigens based on conserved proteins required for colonization
name the 3 current pneumococcal vaccines
- conjugate vaccines (PCV); purified capsular polysaccharides conjugated to carrier proteins
- PPV23; purified polysaccharides
- adjuvanted with aluminium phosphate; Th2 adjuvant to increase antibody response