7. Pseudomonas

Most P. Aerogenosa infections are acquired from where

Nosocomial

Cystic fibrosis

Genetic disorder caused by mutation of CFTR gene

CFTR gene

Encodes for chloride channel in cells that produce mucus,sweat, tears, saliva

Mutated CFTR gene

When chloride ions aren’t properly transported out of the cell, water balance is disrupted

Why are CF patients at higher risk for p. aeroginosa

Mucus build up prevents cilia from clearing Pseudomonas bacteria, so they get a chronic infection

15% of pseudomonas infections are ____

Multi-drug resistant (MDR-PA)

P. Aerogenosa motility

Single polar flagella

P. Aerogenosa attachment

Type 4 pili

Lipid A of LPS

Endotoxin which is only released when bacterium are dead

Lipid A is considered a

PAMP to induce TLR4 inflammatory response

Most toxic P. Aerogenosa virulence factor

Exotoxin A

Exotoxin A

AB toxin that ADP-ribosylates EF-2 to prevent translation and kill the cell

Why are pseudomonas a blue-green color

Pyocyanin

Pyocyanin

Secreted by T2SS which increases reactive oxygen species, damaging DNA and killing cells. Slows ciliary beating in lungs

Type 3 secretion system in P. Aerogenosa

Has 4 main effector toxins, ExoU, ExoY, ExoT, and ExoS

Exo proteins from T3SS

Not required for infection, BUT found in most clinical isolated and associated with increased disease severity

Phenotypic antibiotic resistance mechanism

Occur because of current state of organism

Intrinsic antibiotic resistance mechanism

Genetically encoded in organism

Acquired antibiotic resistance mechanism

Gain of function genes from other organisms or mutations

Ex of phenotypic resistant

Biofilms

Swarming motility

Persisters (low metabolic rate)

Ex of intrinsic resistance

Efflux pumps

Downreg porins

Drug inactivation

Low membrane permeability

LPS modification

Ex of acquired antibiotic resistance

Acquired efflux pumps

Why are some strains mucoid?

Production of alginate capsule

Alginate

Exopolysaccharide that protects cells from immune system and increases biofilms and severity

LasA and LasB

Elastases which degrade host elastin and matrix proteins to disrupt epithelial cell barrier

Treatment of MDR-PA

Carbapenum is last line antibiotic

Penicillin binding protein

Required component of bacterial cell wall

Penicillin

Binds to and inactivates penicillin binding proteins

Penicillin, carbapenum, and cephalosporins

Beta-Lactam drugs which have beta lactam ring

P Aerogenosa AmpC

Beta lactamase which degrade beta lactam antibiotics

Penicillins

Ampicillin, amoxicillin

Cephalosporins

Ceftriaxone, cephalexin

Intrinsic resistance of P. Aerogenosa

Low membrane permeability

Efflux pumps

Downreg. Poring

LPS modifications

P. Aerogenosa LPS modification

TCS senses polymyxin and alters gene expression involved with LPS synthesis

Polymyxin

Antibiotic that binds and neutralizes LPS to disrupt cell membrane

Acquired antibioticesistance in p. Aerogenosa

Upreg efflux pumps

Downreg porins

Drug inactivation (beta lactamase)

Target modification via DNA mutation

Frequent nosocomial infections

S. Aureus

P. Aeroginosa

E. Coli

A. Baumanii

Outer membrane vesicles (OMVs)

Small membrane blebs from GRAM NEGATIVE cell surface which can be offensive or defensive

Offensive OMVs

Delivering virulence factors to host cells like LPS and flagellin or damaging proteins

Defensive functions of OMVs

Gets rid of porins

Act as decoy for PHAGES

How is OMV expression regulated in p. Aeroginosa

Quorum sensing

Common quorum sensing system in p. Aero

LasI-LasR

LasI

Makes asyl-homoserine lactose (AHL) to diffuse across membrane

LasR

Detects AHL and acts as transcription factor to control 3 other QS systems

Why is iron availability in the host so low?

Iron is bound by host proteins transferrin and lactoferrin

How does p. Aero acquire host iron

Siderophores bind to iron ions which high affinity

Siderophores of p. Aero

Pyochelin

Pyoverdine

Main Siderophore in p. Aero

Pyochelin

Pyoverdine

More efficient at binding to iron BUT requires more energy and produces ROS so only used in stressful low iron conditions