Lecture 29 - Pseudomonas aeruginosa

Question 1

Describe Ps. aeruginosa

Answer 1

• Aerugo = copper rust/verdigris
• G-ve rod, aerobic, non spore, flagellum, an/aerobic, diverse metabolism, 5.5-7Mb
• range of transporters, 2 component systems and regulators with HGE between species

Question 2

where is ps. aeruginosa found

Answer 2

• Soil, water, plants, mammal gut, habitats contaminated by humans
  Reservoirs = human/animal faeces, urban eg hot tubs and pools, hospitals eg water systems and disinfectants

Question 3

describe the clinical manifestation of Ps. aeruginosa in healthy patients

Answer 3

○ Hot tub folliculitis
○ Puncture wounds in feet
○ Swimmer’s ear

Question 4

describe the clinical manifestation of Ps. aeruginosa in immunocomp patients

Answer 4

○ Cystic fibrosis
○ Burn wound infections = blue-green purulent discharge (pyocyanin)
○ Diabetes = malignant otitis externa
○ Organ transplant recipients/ICU patients = pneumonia, UTIs, bacteraemia
- Invasive devices = indwelling devices @ risk bc biofilms

Question 5

list the 8 VFs of Ps. aeruginosa

Answer 5

1. polar flagellum = adhere and colonise
2. type 4 pilus = twitching motility, adhesion
3. EPS = alginate, Psl, Pse = biofilm
4. T3SS = cytotoxic ExoUTSY
5. T2SS = exotoxin ETA inhibiting protein synth, elastase, lipase, phospholipase C, esterase, pyocyanin
6. siderophores = pyoverdine and pyochelin
7. antioxidant enzymes = KatABE
8. QS x4 = C12HSL, C4HSL, PQS

Question 6

List the 4 step cystic fibrosis pathway of Ps. aeruginosa

Answer 6

1. intrinsic antibiotic tolerance
2. pathoadaptative mutations
3. phenotypic convergence
4. infection progression

Question 7

describe the intrinsic antibiotic tolerance step of CF

Answer 7

most die, some survive by mechanisms + intrinsic antibiotic tolerance = evade immune = colonise mucus layer

Question 8

describe the pathoadaptative mutation step of CF

Answer 8

selective pressures = mutations for expansion of heterogenous adapted populations = increased bacterial load + genetic diversity

Question 9

describe the phenotypic convergence step of CF

Answer 9

loss of flagella and VFs, aggregative lifestyle ie multicellular, specialise metabolism for low nutrients/O2, mechanisms for antibiotic resistance

Question 10

describe the infection progression step of CF

Answer 10

continuous inflammation activation + bacterial activity = tissue dmg/deterioration

Question 11

define tolerance

Answer 11

persistence = survival with antibiotic without increasing min inhibitory conc (MIC) = no/slow growth with antibiotic

Question 12

what 4 ways are biofilms tolerant of antibiotics?

Answer 12

1. slow penetration
2. upreg efflux pumps
3. Altered microenviron = decreased pH + accumulated wastes antagonises antibiotics
4. Persistence = subset survives exposure to bactericidal drug conc

Question 13

how is tolerance favoured?

Answer 13

high antibiotics + growth restrictions

Question 14

how is resistance favoured?

Answer 14

high growth nutrients + low antibiotics

Question 15

how does Ps. aeruginosa develop resistance? provide an example

Answer 15

• mutations or HGT
• mutSL in DNA repair mutations = increased mutation frequency = increased resistance possibility

Question 16

what are ESKAPE pathogens? list a few

Answer 16

• Bacteria associated with antimicrobial resistance = major global health threat
  eg Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.

Question 17

how does Ps aeruginosa inactivate beta lactams and aminoglycosides?

Answer 17

• beta lactamases
• add amines/hydroxyl/methyl groups to aminoglycoside target ie 16S rRNA

Question 18

describe the 3 ways ESKAPE pathogens incl Ps. aeruginosa resist antimicrobials

Answer 18

1. Antimicrobial inactivation = beta lactamases and target modification
2. Persistence = biofilms
3. Reduced antibiotic accumulation = mutated porins and upreg efflux pumps