Significance of Metallo-β-Lactamase in the Emergence of Carbapenem-Resistant Pseudomonas aeruginosa: Future Prospective Ways to Evade Resistance Emergence

The worldwide emergence of Carbapenem-resistant Pseudomonas aeruginosa has become a global threat to public health, the clinical industry, the food industry, and the global economy as Carbapenm is the last resort drug for Multi-drug resistant Pseudomonas aeruginosa [25, 28]. Pseudomonas aeruginosa is a gram-negative bacilli ubiquitously found in nature that causes serious nosocomial infections increasing the severity of the health condition of hospitalized patients and adding to morbidity and mortality. Recent studies have discovered the emergence of Metallo-beta-lactamase genes in CRPA as a critical issue behind the rapid spread of CRPA strains internationally. Along with intrinsic mechanisms, CRPA strains have been found to contain these MBL genes in mobile genetic elements with other antibiotic- resistant genes, exacerbating the situation [3, 5, 29-31, 37, 38, 49]. In this study selected studies have been discussed that have been published in the last ten years in India to understand the epidemiological situation of our country on the significance of MBL genes in CRPA emergence. Furthermore, the impact of it on a global scale can also be delineated. It not only helps to understand the issues in-depth but also, to address the current approaches by which the resistance can be avoided without the constant need for another novel antibiotic. Antibiotic dosage abuse is another crucial factor in the MDRPA emergence [34]. There are multiple novel approaches being studied around the world. Chitosan-encapsulated POMs (Polyoxometalates) are one such solution that shows very promising potential. It is also a cheaper, easily produced, malleable, and bio-sustainable option than other available nanoparticle therapies. This nano-system can work as a suitable drug delivery system for Carbapenem by releasing the desired drug in a dose-dependent manner as well as containing self- antibacterial activity itself, efficient to combat both intrinsic and extrinsic resistance mechanisms in CRPA. Additionally, it can show efficiency in breaking the biofilm barrier created by many CRPA strains as an additional resistance mechanism [27, 41, 43]. The efficiency of the tiny drug carriers can be enhanced many times by immobilizing phage-encoded Tail Spike Proteins on them. This can confirm a targeted delivery of Carbapenem to treat MDRPA and reduce the chances of further emergence of CRPA strains [65, 66, 67]. This review article focuses on the potential of this newer approach to solve the ongoing CRPA issue.