Lecture 14 Pseudomonas and Chronic Infection Flashcards
What are Pseudomonas?
- Large, diverse genus within the gammaproteobacteria
- Found in a huge range of environments and climes (water, soil, air)
- Includes plant pathogens and commensal
- By and large do not cause disease in humans
- Pseudomonas species are frequently encountered as contaminants in the clinical laboratory
How do Pseudomonas become pathogens?
- are commensal, tiny fraction opportunistic, can exploit immunocompromised individuals
What is the opportunistic Pseudomonas?
P. aeruginosa
What is unique about P stutzeri?
Forms a coral reef colony
How is P aeruginosa Identified?
- Long, narrow GNR
- Oxidase + (differentiates from Enterobacteriaceae)
- Grows well at 42°C (optimally at 37°C, themo resistant)
- non-lactose fermenter
- Non-spore forming
- Beta hemolytic
- Aerobic
- Motile (single, polar flagellum)
What are the giveaways of P aeruginosa?
- smell likes grape or corn chips
- Metallic sheen on agar due to pigment
- Pyocyanin (blue-green) is typical
- serve as siderophores
What is unique about pyocyanin?
It is fluorescent under UV.
Where is P aeruginosa found?
They are found everywhere, Ubiquitous organism. Once found on flowers in hospital.
What is Hot tub folliculitis?
- Aka P. aeruginosa folliculitis
- Superficial infection of hair follicle root
- Inoculation from contaminated water (frequently hot tubs or swimming pools)
- Usually clears on its own, can treat with antibiotics
What is Swimmer’s ear?
- Aka Otitis Externa
- Superficial infection of external ear canal skin
- Inoculation from contaminated water
- Topical antibiotics indicated
What can P. aeruginosa cause in Sick/elderly/immunocompromised?
- UTI
- Pneumonia
- Wound infection (burn victims)
- Individuals with cystic fibrosis can cause chronic pulmonary infection.
How is CF caused?
is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) protein, which regulates flow of water and Cl out of cell. This causes inefficient pumping, leading to thick mucous.
What are some major sx of CF?
- Pulmonary infections
* Pancreatic dysfunction and poor nutrition
How do people get CF?
-Genetic, common in caucasian. One of the most common inherited disease and can be highly fatal.
What is the pathophysiology of CF?
- Thick mucus builds up in airway
- Colonized by bacteria
- Causes chronic infection
- Progressive lung function decline
- Baseline vs. “exacerbation”
What are some treatments for CF?
- abx therapy to keep bacterial burdens in check (inhaled vs. systematic)
- Pulmonary hygiene
- Uncommon cases (lung transplant, CFTR potentiation)
P aeruginosa is a major cause in what?
acute and chronic infections
What is the relation of P aeruginosa and CF?
- Predominant lung pathogen in CF
- typically the same infecting strain persists in the lung for years or decades. Undergoes adaptive changes.
What was discovered when a CF lung was dissected?
-different regions had descendents form the same initial clone, but different phenotypes. Genetic lineages evolved over time, up to 600x the amount of divergence per year.
Does the one-size fit all abx therapy work on P aeruginosa?
No because so diverse.
What are important virulence factors of P. aeruginosa?
- biofilm formation
- mucoid phenotype
- Also (do not to need to know specifics) Iron sequestration, exotoxins, proteases.
What is a biofilm?
-is a multicellular collection of bacteria which form a 3-dimensional structure on a surface.
• Predominant form of bacteria in the environment
What are the steps of biofilm formation?
1) Initial reversible attachment of free swimming microorganisms to surface
2) Permanent chemical attachment, single layer, early matrix production 3) Early vertical development
4) Multiple towers with channels between, maturing biofilm
5) Mature biofilm with seeding / dispersal of more free swimming microorganisms
What is the competitive advantages of biofilms?
• Increased antibiotic resistance
- resistance to host
- enhanced adherance
What is important of biofilms?
-inherently abx resistant. Can show up to 1000x increase.
What is the mech of resistance in biofilms?
- changes in gene expression.
- center is nutrient limited and metabolically inactive (dormant).
How does the mucoid phenotype made?
- overproduces alginate
- important adaptive change for chronic infection.
- make capsule
What are consequences of mucoid phenotype?
- gives biofilm structural support
- enable micro-metastasis
- binds abx
- protects against host response
How big is P aeruginosa genome?
- when first sequenced, largest bacterial genome sequenced.
- give a lot of flexibility and resistance
- now a lot of strains have been sequenced
Genetic differences in bacteria are…?
- greater than differences in humans.
- Single nucleotide polymorphisms (SNPs) are large contributor to human and bacterial variation.
Bacterial differences can be..?
variably present or absent in different strains of the same species.
What is the concept of bacterial “ Pan-genome”?
Defines the entire possible genetic content of a bacterial species.
The pan-genome is far larger than the genomic content of any single strain.
-Both core and accessory.
What is the Core genome?
Genes essential to that organism. Define what organism is.
What is Accessory genome?
Genes that MAY be advantageous. Define what organism can do.
What is the Pan genome Core genome analogy?
Pan Genome= bells and whistles
Core genome= life support functions.
What is important of the Pan-genome of P. aeruginosa?
-Antibiotic resistance genes and virulence islands make up a big fraction of the accessory genome
