Treatment

Question 1

For best treatment outcomes what should be done quickly?

Answer 1

To increase the likelihood of treatment being a success we must ensure that there is rapid diagnosis of P.aeruginosa infection

Question 2

Culture dependent methods of diagnosis require samples. How can the samples be obtained?

Answer 2

Nasal swaps
Samples from throat and cough
However, these are not predicative of lower airway infection
Can perform a broncioalveolar lavage.

Question 3

Issues with a bronchioalveolar lavage?

Answer 3

Can be invasive

Requires anaesthetic

Question 4

What are some culture independent methods of diagnosis?

Answer 4

16S rRNA sequencing
Measuring IgG antibodies against P.aeruginosa
Breath analysis using mass spectrometry for volatile compounds indicative of P.aeruginosa infection such as HCN- hydrogen cyanide

Question 5

What are some novel methods of treatment?

Answer 5

• Trojan horse antibiotic treatment
• Monoclonal antibodies against PcrV
• Monoclonal antibodies against LPS
• Phage therapy
• Anti-biofilm treatment
• Inhibition of quorum sensing through molecular mimicry

Question 6

Trojan horse strategy?

Answer 6

Often difficult for antibiotics to penetrate the biofilm and to reach target cells
Can hijack the iron-siderophore uptake
Can form antibiotic-siderophore complexes by using a linker
The antibiotic will then be taken up more easily by binding siderophore receptors

Question 7

Antibodies against PcrV?

Answer 7

PcrV is found at the tip of the needle of the T3SS
Antibodies against PcrV will prevent the needle engaging with the eukaryotic cell
Will ultimately prevent toxic effectors being injected into eukaryotic cells

Question 8

Anti-biofim treatment?

Answer 8

The biofilm is made up of exopolysaccharides
If we have enzymes which can break down the exopolysaccharides we will better be able to target the bacteria with antibiotics etc…

Question 9

What are examples of enzymes which can break down exopolysaccharides?

Answer 9

Alginate lyase

Glycoside hydrolase

Question 10

What are the advantages of phage therapy?

Answer 10

• Self-dosing- will increase in number until all the bacteria have been cleared
• Resistance is unlikely to develop as the phage can mutate and evolve too
• Specific and will not destroy gut commensals like antibiotics
• Can reach places that antibiotics cannot such as the blood brain barrier and bone infections
• Can be taken in a pill form without reducing the efficacy

Question 11

What are the disadvantages of phage therapy?

Answer 11

• Unforeseen consequences
• May elicit an immune response
• Specific which means diagnosis of the causative bacterium is required before administration
• Only lytic phages can be used, due to the risk of resistance transfer etc…