Antimicrobial Mechanisms and Mode of Actions of Nanoemulsion Against Drug-Resistant ESKAPE Pathogens

Introduction

In recent years, antimicrobial resistance (AMR) is one of the major health concerns around the world. According to the World Health Organization (WHO), AMR poses a major threat to the treatment of bacterial infections because the greater intake of drugs has led to an increase in the incidence of incorrect use of antibiotics leads to increased morbidity and mortality. Rapid increases in resistance and a downturn in the introduction of new antibiotic groups have severely limited existing therapeutic options for multidrug-resistant (MDR) pathogens (Gelband et al., 2015). The increase in the rate of drug resistance in bacterial infections and prevalence of MDR bacteria have been closely linked to the use of broad-spectrum antibiotics. Some Gram-positive and Gram-negative bacteria have developed resistance to not only commonly used antibiotics, but also to whole classes of antibiotics (Nikaido, 2009). A growing category of multidrug resistant human pathogenic bacteria mentioned as ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp), are capable of “escaping” the biocidal action of antimicrobial agents and commonly recognized as hospital acquired pathogens (Rice, 2008). Persistent use of antibiotics has provoked the emergence of MDR in pathogenic microorganisms including extended spectrum b-lactamase (ESBL) and carbapenemase producing bacteria, which render even the effectual drugs unsuccessful. According to the urgent need of new antimicrobials, these pathogens are describing three categories as critical, high and medium priority. Carbapenem-resistant A. baumannii and P. aeruginosa, as well as extended spectrum ESBL and carbapenem-resistant K. pneumoniae and Enterobacter spp are on the critical priority catalog of pathogenic bacteria, whereas vancomycin-resistant E. faecium (VRE) and methicillin- and vancomycin-resistant S. aureus (MRSA and VRSA) are in the list of high priority group of the need. Under the research investigation, ESKAPE pathogens showed mechanisms of multidrug resistance are broadly grouped into three evidences as, modification of the target site where the antibiotic may bind, drug inactivation by an irreversible cleavage that is catalyzed by the presence of enzyme, reduced drug absorption due to lower permeability or increased drug efflux system (Santajit and Indrawattana, 2016). The current therapeutic options for the treatment of multidrug-resistant pathogens have been severely limited. Collectively, due to the danger infectious nature of these pathogens resulted in the strong demand of new antimicrobials as alternative therapies that are currently in practice (Gelband et al., 2015).

A special interest has been developed by the scientific community to treat drug resistant infections, particularly those caused by ESKAPE pathogens through the use of nanoemulsions. Essential oils (EOs) are aromatic oily natured liquids obtained from plant material. The most active components of EOs include flavonoids, monoterpenes, phenyl propanoids and polyunsaturated omega-6-fatty acids (Franklyne et al., 2016). The medicinal properties of essential oil based nanodroplets usually in the range of 10–100 nm size, have received a great interest for the reason that of their low toxicity, kinetically stable properties, isotropic, transparent, pharmacokinetic activities and economic feasibility (Chouhan et al., 2017). The attempt to formulate a potential nanoemulsion with multiple potential targets or complex mechanisms as well as desirable biological and physicochemical properties, advanced the area of research to develop innovative antimicrobials. The cell membrane of bacteria made-up of phospholipid bilayers contains charged lipids with high binding efficiency and the potential for electrostatic attraction (Krishnamoorthy et al., 2018).