Cracking the Challenge of Antimicrobial Drug Resistance with CRISPR/Cas9, Nanotechnology and Other Strategies in ESKAPE Pathogens

Abstract

Antimicrobial resistance is mushrooming as a silent pandemic. It is considered among the most common priority areas identified by both national and international agencies. The global development of multidrug-resistant strains now threatens public health care improvement by introducing antibiotics against infectious agents. These strains are the product of both continuous evolution and unchecked antimicrobial usage (AMU). The ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are the leading cause of nosocomial infections throughout the world. Most of them are now multidrug-resistant, which pose significant challenges in clinical practice. Understanding these bacteria’s resistance mechanisms is crucial for developing novel antimicrobial agents or other alternative tools to fight against these pathogens. A mechanistic understanding of resistance in these pathogens would also help predict underlying or even unknown mechanisms of resistance of other emerging multidrug-resistant pathogens. Research and development to find better antibacterial drugs and research on tools like CRISPER-Cas9, vaccines, and nanoparticles for treatment of infections that can be further explored in the clinical practice health sector have recognized these alternatives as essential and highly effective tools to mitigate antimicrobial resistance. This review summarizes the known antimicrobial resistance mechanisms of ESKAPE pathogens and strategies for overcoming this resistance with an extensive overview of efforts made in this research area.

Comparison of CRISPR–Cas Immune Systems in Healthcare-Related Pathogens

“…ESKAPE pathogens are the primary cause of nosocomial infections (infections contracted from a healthcare setting) and are of global concern due to the increasing emergence of multi-drug resistant (MDR) bacteria (Zohra et al, 2021 ). The term ESKAPE pathogens was first coined by Rice (Rice, 2008 ) and originally included Staphylococcus aureus, Enterococcus faecium, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa , and Enterobacter spp.…”

“…They are now attributed to the majority of US hospital infections and effectively “escape” the limited bank of available antibiotics by acquiring antimicrobial resistance (AMR) genes. The threat of multi-drug resistant bugs is constant and has fueled a variety of research and surveillance efforts (Zohra et al, 2021 ).…”

Biofilm and Small Colony Variants—An Update on Staphylococcus aureus Strategies toward Drug Resistance

“…Antibiotic-resistant infections are capable of inducing morbidity and raising mortality [38][39][40]. The majority of nosocomial infections are caused by the ESKAPE pathogens, including Enterococcus faecium, S. aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species, most of which possess multidrug-resistance [3]. In particular, the rise of super-bacteria has been observed for a while, which sounds another alarm for global health [41].…”

“…In the past decades, antibiotics have played a significant role in reducing the risks involved in childbirth, injuries, and intrusive medical procedures [1,2]. However, abuse or overuse of antibiotics in the circumstances of experimental studies and clinical treatments poses a severe threat to public health by acquiring drug-resistance (DR) and multidrugresistance (MDR) of the pathogens [3,4]. It is of great concern that if the growing resistance to antibiotics continues, the global economies will suffer a sharp loss of USD 100 trillion by 2050 [5].…”

Translational potential of base-editing tools for gene therapy of monogenic diseases

“…The CRISPR/Cas9 system has opened up numerous opportunities for genome editing in different organisms, and now there are many reports on its various applications [for review see ( Mengstie and Wondimu, 2021 )]; in particular, this system is used to create animal models of human diseases ( Leonova and Gainetdinov, 2020 ). It has found many applications in biotechnology, including cracking the challenge of antibiotic resistance ( Matharu et al, 2019 ; Novick, 2021 , 202; Zohra et al, 2021 ). For instance, the use of a CRISPR-Cas9 system targeted against resistance genes has helped to reduce the resistance to β-lactames in E. coli ( Kim et al, 2016 ) and K. pneumonia ( Hao et al, 2020 ) and to lower the number of antibiotic-resistant E. faecalis strains ( Rodrigues et al, 2019 ).…”