Relationship between OprD porin downregulation and in-vitro interactions in Pseudomonas aeruginosa

Abstract

Introduction: OprD porin plays a critical role in antibiotic uptake. However, the role of OprD in antimicrobial interactions is not yet fully understood. This study investigated the relationship between OprD downregulation and in vitro interactions of meropenem (MEM) with combinations of colistin (CT), ertapenem (ETP), and fosfomycin (FF) in Pseudomonas aeruginosa.

Methodology: A total of 40 P. aeruginosa isolates were included in the study and divided into two groups (group-1, 20 isolates with confirmed OprD suppression; group-2; 20 isolates without OprD suppression). Antimicrobial interactions were examined using the checkerboard method.

Results: The synergy rates of MEM/CT, MEM/ETP, and MEM/FF combinations in group-1/group-2 isolates were determined as 45%/30%, 5%/5%, and 15%/10% respectively. The minimum inhibitory concentration (MIC) of antimicrobials in combinations were examined for group-1 and group-2 isolates, and a decrease of 90%, 90% for MEM and 70%, 40% for CT was detected in the MEM/CT combination, 50%, 45% for MEM and 35%, 40% for ETP in the MEM/ETP combination, and 35%, 20% for MEM and 55%, 45% for FF in the MEM/FF combination, respectively.

Conclusions: While significant synergy was observed between MEM/CT in OprD-deficient isolates, the limited synergistic effects observed with other combinations, such as MEM/ETP and MEM/FF, suggest that the impact of OprD downregulation on antimicrobial resistance is multifactorial and complex. The findings suggest that CT, when combined with MEM, may overcome certain resistance mechanisms mediated by OprD downregulation. Further investigations incorporating molecular diagnostics and in vivo validation are warranted to fully elucidate the therapeutic potential of these combinations.