Antibiotic-Resistant Pseudomonas aeruginosa: Current Challenges and Emerging Alternative Therapies

Abstract

Antibiotic-resistant Pseudomonas aeruginosa is a pathogen notorious for its resilience in clinical settings due to biofilm formation, efflux pumps, and the rapid acquisition of resistance genes. With traditional antibiotic therapy rendered ineffective against Pseudomonas aeruginosa infections, we explore alternative therapies that have shown promise, including antimicrobial peptides, nanoparticles and quorum sensing inhibitors. While these approaches offer potential, they each face challenges, such as specificity, stability, and delivery, which require careful consideration and further study. We also delve into emerging alternative strategies, such as bacteriophage therapy and CRISPR-Cas gene editing that could enhance targeted treatment for personalized medicine. As most of them are currently in experimental stages, we highlight the need for clinical trials and additional research to confirm their feasibility. Hence, we offer insights into new therapeutic avenues that could help address the pressing issue of antibiotic-resistant Pseudomonas aeruginosa, with an eye toward practical applications in future healthcare.

Keywords: CRISPR; Pseudomonas aeruginosa; antibiotic resistance; antimicrobial peptides; bacteriophage; nanoparticle.

Figure 1

Persistent cell and adaptive cell mutation mechanisms. By slowly penetrating into the biofilm matrix (green), antibiotics (red) gradually add selective pressure on biofilm bacteria. Some bacteria cells inside the biofilm develop adaptive mutation (yellow) in a harsh environment. Antibiotic existence alters the microenvironment of biofilm, which leads to a bacteria mutation helping to export antibiotics (dark green). In the meantime, MDR persister cells are formed (light green).

Figure 2

Mechanisms of phage therapy and its combinational methods against P. aeruginosa biofilms. (A) Phages can penetrate into the biofilm effectively and eliminate resident bacteria. (B) Phages inhibit biofilm formation by inhibiting QS and reducing cellular communication. (C) Combined use of phages and other bacteria-growth-limiting chemicals (antibiotics, nanoparticles, QSI, etc.).