lecture 15 - biofilms & cystic fibrosis Flashcards
What is a biofilm?
An aggregation of bacteria in which cells are embedded in a self-produced matrix of polymeric substances that allow adherence between bacteria and to the surface
What is the predominant mode of bacterial growth in chronic infections?
Biofilms
What does the host contribute to biofilm structures?
Fibrin and mucus
How are biofilms more tolerant to antimicrobials?
They have a physical barrier to the drugs, and also have slow metabolic growth, while antimicrobials tend to target rapidly dividing cells.
What are planktonic bacteria?
Bacteria that are living freely/on their own as opposed to in a biofilm
What mechanism is used to regulate biofilm formation?
Quorum sensing
How is biofilm formation regulated by quorum sensing?
Bacteria produce autoinducers that regulate biofilm protein expression. Increasing concentrations of bacteria will increase the concentration of the autoinducer until a threshold is met, when a biofilm is made.
What gene is implicated with cystic fibrosis?
CFTR (Cystic Fibrosis Transmembrane conductance Regulator gene)
What is a CFTR protein?
An ATP-gated cAMP regulated chloride ion channel found in epithelial cells
What is the normal function of a CFTR channel?
Moves chloride ions out of epithelial cells to the covering mucus
What are the effects of a CFTR mutation?
There id reduced chloride channel secretion, and therefore increased Na+ absorption, resulting in thickening of the mucus
What is the pattern of inheritance of cystic fibrosis?
Autosomal recessive
What are the signs and symptoms of cystic fibrosis?
Failure to thrive, obstructive pulmonary disease, recurrent chest infections, persistent cough, lung hyperinflation, infertility
Why does mucus build up in the airways with cystic fibrosis?
Decreased Cl release leads to increased Na and H2O absorption from mucus, thickening it and making it more difficult to clear from the airways.
What is the most significant bacterial infection in patients with Cystic Fibrosis?
Pneumonia with Pseudomonas aeruginosa
What is the key virulence factor of Pseudomonas aeruginosa?
Biofilms - allows for chronic infection
Why is Pseudomonas aeruginosa so difficult to treat with antimicrobials in CF patients, resulting in chronic infection?
With each acute infection there is genetic adaptation, resulting in clonal selection of a dominant clone that evades antimicrobial treatment
What mechanisms does Pseudomonas aeruginosa have to evade the CF hosts immunity?
Biofilm growth, produces mucoid coating to evade phagocytes
What are the consequences of P. aeruginosa switching to the mucoid type in a host with CF?
Mucoid form produces an alginate matrix, which the body produces antibodies to, resulting in a chronic inflammatory response that damages the lungs
What are the treatments for infections in CF?
regular surveillance cultures, inhaled eradications for acute or chronic infections
What is a rising group of bacteria that is affecting more and more CF patients?
Non-tuberculous mycobacteria, e.g. M. avium & M. abscessus
