micro 3 Flashcards
how many different mutation has been found of the CFTR protein?
over 1800
what is the most common CFTR mutation?
Phe508del most common (>80% of cases)
what is the mucocillary elevator?
- Cilia in the lung beat which then moves mucus up to the throat and swallowed
- Cl-secreted into ASL via CFTR
what happens in the mucocillary elevator in someone with CF?
In Phe508del CF, CFTR protein absent
•Cl-cant be pumped out
•ASL dehydrates, mucus attracted to cell surface and cilia unable to beat properly
•Mucus becomes stuck
what are the comvectional CF pathogens?
P. aeruginosa
S. aureus
H. influenzae
B. cepaciacomplex
how does the prevalence of microorganisms differ?
varies by country-•MRSA in adults: UK ~3%; USA >30%
what did Muhlebachet al 2018 find in his study?
- Took BAL samples and looked at different types of microbes (particularly bacteria in lung) using 16s rRNA sequencing
- Initial microbial load is similar to that found in oral cavity
- Transitions to pathogen dominated by age 4
how do bacteria change in infections in CF patients over time?
- Initially with H. influenza and S. aureus
* Progresses to intermittent and chronic P. aeruginosa
what are the two main types of Staphylococcus aureus that are in CF infections in the lung?
- MRSA
* Small colony variants (SCV)
how big are small colony variants?
<1mm, nonpigmented, non haemolytic
what happens if the growth rate decreases in small colony variants?
increased resistance
what are the clinical implications of scv?
Children with SA SCV had lower mean % of predicted FEV1(85.5% Vs 92.4%)
•SCVs which were thymidine dependent →strongest association with lung function
what is Pseudomonas aeruginosa?
Gram negative facultatively anaerobic bacillus •Environmentally ubiquitous, generally an opportunistic pathogen
•Found in UTIs, sepsis, non-CF lung infections, GI etc
what is the main priority on WHO list of antibiotics to make?
Pseudomonas aeruginosa
Intrinsically resistant to multiple antimicrobials;
•Multiple efflux systems
•Multiple secreted and cell based virulence factors
what is Pseudomonas aeruginosa’s role in CF?
Generally thought of as an opportunistic pathogen;•Several groups of strains have become more specialised pathogens and are associated with CF infection
how can New infections with PA can be eradicated?
- Combination of oral/IV antibiotics AND inhaled antibiotic
- Non consensus on what is the best combination
- Can be successful in approx. 80% of cases
what is Chronic colonisation with PA associated with?
- Worse lung function outcome
* Higher inflammation
how does Pseudomonas aeruginosa adapt in the CF lung?
- Has to overcome challenges in the CF lung•Protection from immune system•Less oxygen in mucus layer
- Switches gene expression•Begins to adapt•Numerous mechanisms
how are the PA adaptations in the lung regulated?
Many of the changes are regulated by quorum sensing system
what is Quorum sensing?
Ability to detect and respond to cell population density by gene regulation
•Expression or repression of specific genes which produce phenotypes which will be beneficial
what are the 3 characteristics bacteria must have to be able to us QS?
- Ability to produce a signalling molecule (an autoinducer)
- Be able to detect the change in [signalling molecules]
- Regulate gene expression as a result
how can PA use QS?
- Biofilm formation
* EPS production
what is type 3 secretion system?
- T3SS is needle like machinery that lets bacterial effectors translocate directly into the cell
- Causes tissue injury and cytotoxicity
- Can also activate innate immune response via IL-1β
- Chronic PA infections select against T3SS expressing PA
what are the 4 T3SS dependent effectors PA has?
- ExoS, ExoT, ExoY, and ExoU(reviewed in Hauser, 2009)
- ExoS, T and U disrupt host cell cytoskeleton
- ExoUcan cleave phospholipases (leads to cell death)
