lecture 15 - biofilms & cystic fibrosis

Question 1

What is a biofilm?

Answer 1

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

Question 2

What is the predominant mode of bacterial growth in chronic infections?

Answer 2

Biofilms

Question 3

What does the host contribute to biofilm structures?

Answer 3

Fibrin and mucus

Question 4

How are biofilms more tolerant to antimicrobials?

Answer 4

They have a physical barrier to the drugs, and also have slow metabolic growth, while antimicrobials tend to target rapidly dividing cells.

Question 5

What are planktonic bacteria?

Answer 5

Bacteria that are living freely/on their own as opposed to in a biofilm

Question 6

What mechanism is used to regulate biofilm formation?

Answer 6

Quorum sensing

Question 7

How is biofilm formation regulated by quorum sensing?

Answer 7

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.

Question 8

What gene is implicated with cystic fibrosis?

Answer 8

CFTR (Cystic Fibrosis Transmembrane conductance Regulator gene)

Question 9

What is a CFTR protein?

Answer 9

An ATP-gated cAMP regulated chloride ion channel found in epithelial cells

Question 10

What is the normal function of a CFTR channel?

Answer 10

Moves chloride ions out of epithelial cells to the covering mucus

Question 11

What are the effects of a CFTR mutation?

Answer 11

There id reduced chloride channel secretion, and therefore increased Na+ absorption, resulting in thickening of the mucus

Question 12

What is the pattern of inheritance of cystic fibrosis?

Answer 12

Autosomal recessive

Question 13

What are the signs and symptoms of cystic fibrosis?

Answer 13

Failure to thrive, obstructive pulmonary disease, recurrent chest infections, persistent cough, lung hyperinflation, infertility

Question 14

Why does mucus build up in the airways with cystic fibrosis?

Answer 14

Decreased Cl release leads to increased Na and H2O absorption from mucus, thickening it and making it more difficult to clear from the airways.

Question 15

What is the most significant bacterial infection in patients with Cystic Fibrosis?

Answer 15

Pneumonia with Pseudomonas aeruginosa

Question 16

What is the key virulence factor of Pseudomonas aeruginosa?

Answer 16

Biofilms - allows for chronic infection

Question 17

Why is Pseudomonas aeruginosa so difficult to treat with antimicrobials in CF patients, resulting in chronic infection?

Answer 17

With each acute infection there is genetic adaptation, resulting in clonal selection of a dominant clone that evades antimicrobial treatment

Question 18

What mechanisms does Pseudomonas aeruginosa have to evade the CF hosts immunity?

Answer 18

Biofilm growth, produces mucoid coating to evade phagocytes

Question 19

What are the consequences of P. aeruginosa switching to the mucoid type in a host with CF?

Answer 19

Mucoid form produces an alginate matrix, which the body produces antibodies to, resulting in a chronic inflammatory response that damages the lungs

Question 20

What are the treatments for infections in CF?

Answer 20

regular surveillance cultures, inhaled eradications for acute or chronic infections

Question 21

What is a rising group of bacteria that is affecting more and more CF patients?

Answer 21

Non-tuberculous mycobacteria, e.g. M. avium & M. abscessus