Fit and resistant is a worst case scenario with bacterial pathogens

Abstract

Pseudomonas aeruginosa is a prevalent nosocomial pathogen (1) and a threat in neonatal and intensive care units, causing deadly infections in ventilator-associated pneumonia or immunosuppressed patients. P. aeruginosa strains causing these infections are frequently multiresistant, and treatment is a nightmare for clinicians (2). P. aeruginosa colonizing the lungs of cystic fibrosis patients cannot be eradicated even after intensive antibiotic therapy. Combinatorial therapies make use of β-lactams, colistin, fluoroquinolone, or aminoglycosides, but resistance to these drugs keeps emerging at high rate, except for colistin. The acquisition of resistance happens via mutations or acquisition of new functions by horizontal gene transfer. The downside for bacteria acquiring resistance is a pay back in fitness cost. Antibiotics target vital cell functions, such as protein synthesis, DNA supercoiling, or integrity of the cell envelope, and compensatory mutations may result in these features not being reliable (3). This is good news and suggests that once the selective pressure of antibiotic treatment ceased, the resistant strains could be outcompeted by strains that are not resistant but fitter, which will be a stumbling block to the spread of multiresistant organisms. However, the work by Skurnik et al. in PNAS (4) demonstrates that a gain of in vivo fitness by P. aeruginosa is due to the lack of the outer membrane protein OprD, and this event correlates acquisition of carbapenem resistance.