Selective imipenem resistance in Pseudomonas aeruginosa associated with diminished outer membrane permeability

Area of Science:

• Microbiology
• Drug Resistance
• Membrane Biology

Background:

• Pseudomonas aeruginosa is an opportunistic pathogen known for its intrinsic and acquired resistance to antibiotics.
• The outer membrane of Gram-negative bacteria acts as a barrier, influencing drug entry and resistance mechanisms.
• Imipenem is a critical carbapenem antibiotic often used to treat multidrug-resistant bacterial infections.

Purpose of the Study:

• To investigate the role of outer membrane permeability in imipenem resistance in Pseudomonas aeruginosa.
• To compare the penetration of imipenem, sugars, and cephaloridine across the outer membrane of susceptible and resistant isolates.

Main Methods:

• Liposome swelling assay was employed to assess the permeability of outer membrane fractions.
• Outer membrane fractions were derived from both imipenem-susceptible and imipenem-resistant clinical isolates of Pseudomonas aeruginosa.
• Differential penetration of various molecules (sugars, cephaloridine, imipenem) was measured.

Main Results:

• Liposomes from imipenem-resistant Pseudomonas aeruginosa isolates showed significantly reduced permeability.
• Sugars and cephaloridine demonstrated rapid penetration into liposomes from both susceptible and resistant strains.
• Imipenem exhibited poor penetration into liposomes constructed from porin-rich outer membrane fractions of resistant isolates.

Conclusions:

• Outer membrane permeability is a key factor contributing to imipenem resistance in Pseudomonas aeruginosa.
• Reduced porin function or expression in resistant strains limits imipenem influx.
• Understanding these permeability changes is crucial for developing strategies against resistant Gram-negative infections.