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Pseudomonas aeruginosa

Pseudomonas aeruginosa is an important pathogen in healthcare-associated infections among critically ill or immunocompromised patients. The pathogen's many virulence factors and its intrinsic and acquired antimicrobial resistance properties enable it to cause diverse diseases. P. aeruginosa is reported as the second most common cause of healthcare-associated pneumonia, the third most common cause of urinary tract infection, and the eighth most common cause of bloodstream infections. 

The Pathogen

Pseudomonas aeruginosa is a ubiquitous, encapsulated, Gram-negative, rod-shaped bacterium that can cause disease in humans, as well as in other animal and plant species.  Well-documented virulence factors of P. aeruginosa include a thick polysaccharide capsule, a type III secretion system that injects toxins into host cells, lipopolysaccharide O-antigen, the redox-active toxin pyocyanin,  a secreted protease (elastase), and a quorum-sensing system regulating biofilm production.

Pseudomonas Infections

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Pseudomonas generally causes infections in immunocompromised or otherwise chronically ill patients, but can occasionally cause skin infections in otherwise healthy people who get trauma in settings of water exposure or in hot tub folliculitis.  Chronic Pseudomonas lung infections are a hallmark of cystic fibrosis, and the pathogen is a common cause of sepsis in burn units and of ventilatory-associated pneumonia. Risk factors for multidrug-resistant P. aeruginosa infections include prior use of antibiotics (especially carbapenems, broad-spectrum cephalosporins, aminoglycosides and fluoroquinolones, extended length of hospital stay, poor functional status (eg. being bedridden), high-level medical care (eg. ICU, mechanical ventilation), active malignancy, or a history of structural lung disease (eg. COPD). 

P. aeruginosa Antimicrobial Resistance

The proportion of P. aeruginosa resistant to carbapenems, quinolones, and third-generation cephalosporins has steadily increased in the last two decades, including multidrug-resistant (MDR) infections (resistance to at least three of four drug classes: carbapenems, ceftazidime, ciprofloxacin and tobramycin). The resistance mechanisms of P. aeruginosa include the production of beta-lactamases, efflux pumps, and target-site or outer membrane modifications; heavily encapsulated (mucoid) strains and those establishing dense biofilms pose additional problems for eradication.

 

3D Map of Diseased CF Lung

Spatial Metabolome and Microbiome Reconstruction

CHARM Investigators used CT scans and spatial sampling to generate the cartography of an end-stage lung from a CF patient where P. aeruginosa dominated. Importantly, not all antibiotics studied show uniform penetration within the lung and that antibiotic metabolism varies spatially.

Read the article Cell Host and Microbe