Pseudomonas aeruginosa

Ιωαννης Γ. Ρούτσιας, Επικ. Καθηγητης Ανοσολογιας/Μικροβιολογιας

Pseudomonas aeruginosa gram-negative non-sporing bacteria Obligate Aerobe, mostly saprophytic Motile

Commonly found in the environment(water, air, soil) At any moist location

Common cause of nosocomial infections

P. aeruginosa (ευκαιριακό παθογόνο) Extremely broad host spectrum Hardly any infections in the normal human host Severe immunodeficiencies and medical devices

predispose the patients to P. aeruginosa infections Broad spectrum of clinical symptoms Urinary tract infections Pulmonary infections Soft tissue infections Sepsis Bone and joint infections Endocarditis

Community Suppurative (πυωδης) Otitis

Hospital

Eye Keratitis and Endophthalmitis

Ear Otitis externa and Otitis media

Skin Burns infection, wound sepsis

UTI Cystitis (catheterized)

RTI Pneumonia (ventilation / tracheostomy)

GIT Infantile (βρεφική) diarrhea

CNS Meningitis brain abscess (iatrogenic)

Diseases (Pathogenicity)

Nosocomial infection

Ecthyma gangrenosum

P. aeruginosa & λοιμώξεις P. aeruginosa infections are of particular concern for Cystic

fibrosis patients

Burn patients

Cancer – cytotoxic drugs

Hospitalised patients Case mortality rate for patients infected with P. aeruginosa

approaches 50%

Νοσοκομειακές λοιμώξεις Fourth most common isolated nosocomial pathogen

accounting for approx. 10 % of all hospital acquired infections. Patient-to-patient spread and direct patient contact with

environmental reservoirs respiratory equipment, food, sinks, taps

Διάγνωση λοίμωξης από P. aeruginosa

Isolation and lab identification of the pathogen P. aeruginosa grows well on most laboratory media Identified on the basis of its: Gram morphology, inability to ferment lactose, a positive oxidase reaction, its characteristic odor(οσμή), Green pigments (Pyocyanin, Flurescein) its ability to grow at 42° C.

Fluorescence is helpful in early identification of P. aeruginosa colonies and may also help identify its presence in wounds.

–Pyocyanin (blue-green) – Fluorescein (green-yellow, fluorescent)

Δοκιμασία κινητικότητας

Θεραπεία των λοιμώξεων από P. aeruginosa

P. aeruginosa is frequently resistant to many commonly used antibiotics.

Antipseudomonad beta lactam Aminoglycoside Fluoroquinolone

To archive synergy a combination of e.g. gentamicin and carbenicillin is frequently used.

No vaccines so far

Μηχανισμοί παθογονικότητας 

Adhesion(Προσκόληση) Pili(κροσσοι), flagella(μαστίγια) and fimbriae(φιμπριες)

Invasion(Διείσδυση) Extracellular enzymes and toxins (proteases, elastase, phospholipases,

rhamnolipids, Exotoxin A) rhamnolipids: glycolipids that kill epithelial cells, kill polymorphonuclear

leukocytes and macrophages and inhibit phagocytosis Exotoxin A blocks protein synthesis by ADP ribosylation of elongation factor

2, thereby triggering cell death

Dissemination (Διασπορά) Leukocidin inhibits neutrophils und leukocytes LPS (Endotoxin)

Protection Capsule (έλυτρο)

Interbacterial Communication

McKnight et al, 2000

Quorum Sensing (Διακυτταρική επικοινωνία βακτηρίων) in P. aeruginosa

Cooperative traits and coordinated behavior of bacteria

Adaptation and survival is facilitated by diversity

„Small colony variants“ (SCV)

SCVs of P. aeruginosa in CF

• Slow growing subpopulations (3% of the P. aeruginosa positive sputum specimens)

• SCVs exhibit an increased resistance towards a broad spectrum of antimicrobial agents

• The recovery of SCV correlates with parameters revealing poor lung function and an inhalative antimicrobial therapy

• Fast growing revertants REV can be isolated from the SCV population

Auto-aggregation in liquid cultures

M. Rohde, GBF Braunschweig

CupA encoded fimbria expression in P. aeruginosa

Molecular Mechanisms controlling the conversion to a SCV biofilm phenotype

Bacterial Biofilms

Biofilms in the environment

Catheter associated biofilms

Chronic biofilm infections

Despite even intensified antibiotic therapy,

no eradication of chronic P. aeruginosa infections of the cystic fibrosis lung

Cystic fibrosis (Κυστική ίνωση) Most common life-threatening inherited genetic disorder in the

Caucasian population Mutation in the cystic fibrosis transmembrane conductance

regulator (CFTR) gene CFTR: ρυθμιστικήπρωτεΐνη πουελέγχειτηνδιέλευσηχλωρίουδιαμέσουτωνμεμβρανώντωνεπιθηλιακώνκυττάρωνδιαφόρωνοργάνωντουσώματοςόπωςτωνπνευμόνων,τουπαγκρέατος,τωνιδρωτοποιώναδένωνκαιτουεντέρου

Περίπου1στα2000‐2500παιδιάεκτιμάταιότιγεννιούνταικάθεχρόνοστηνΕλλάδαμεκυστικήίνωση,ενώτο4‐5%τουπληθυσμούθεωρείταιότιείναιφορείς.

Life expectancy: Until the 1930s: the life expectancy of a baby with CF was only a few months, in the 1980s, most deaths from CF occurred in children and teenagers. Today with improved treatments,

nearly 40 percent of the CF population is aged 18 and older, for a person with CF the median age of survival is nearly 37 years.

Cystic Fibrosis affects a number of organs in the body, cycles of infection and inflammation lead to a progressive deterioration of lung function.

Cystic fibrosis (Κυστική ίνωση) ΜεταλλάξειςστογονίδιοCHTFR προκαλούνμειωμένηπαραγωγήήλειτουργικότητατηςπρωτεΐνηςμεαποτέλεσμαστοεπιθήλιοτωνπροσβαλλομένωνοργάνωνναπαράγεταιπαχύρρευστηκολλώδηςβλένναηοποίααποφράσσειτουςπόρουςτωναδένωνμεσυνέπειατηνπροοδευτικήκαταστροφήτουιστούτωνοργάνων(ίνωση)καιτηντελικήανεπάρκειατους.

Ταάτομαμεκυστικήίνωσηέχουναφύσικαυψηλάεπίπεδαάλατοςστονιδρώτα

Υψηλάεπίπεδαάλατοςεμποδίζουνναδράσουνταφυσικάαντιμικροβιακάπεπτίδια(defensins)ευνοείταιηανάπτυξητηςΨευδομονάδας

Chronic infection of the Cystic Fibrosis lung

Why is traditional antimicrobial therapy ineffective against biofilm bacteria?

The end