Antimicrobial Resistance and Antimicrobial Nanomaterials: An Overview

Introduction

Back in the mid-nineties, the discovery of antimicrobials denotes a profound and remarkable achievement in medicine which was capable of saving lives of millions of populations [1]. Antimicrobial agents, with their static or cidal ability for numerous microorganisms such as bacteria (antibacterials), fungi (antifungals), and viruses (antivirals). Commonly used antimicrobials may be synthetic, may be natural compounds which are modified chemically or may be of animal or plant origin, (Von Nussbaum et al., 2006). Having such variant forms, antimicrobials have a substantial effect on the disease outcome of an infected individual mainly responsible for recovery if they are chosen and used appropriately. Their use ranges from chemotherapy (treatment) to prophylaxis (prevention) of various infections. The history of antimicrobials officially started in 1928, when penicillin, which is the first antibiotics, was discovered. The discovery of penicillin put a major landmark in medicine and started, what is called “the antibiotic revolution” (Davey et al., 2017).

Antibiotics have different mode of actions including the inhibition of cell wall synthesis, inhibition of DNA replication, inhibition of protein synthesis, and alteration or inhibition of metabolism (Awad et al., 2012). In order to behave such mode of actions and access targets located inside the bacterial cell wall, antimicrobials necessarily need to penetrate into the cell. Hence, antimicrobial agents must be capable of penetrating to the site of action which is usually attained by diffusion or by active transport mechanisms. However, antimicrobial agent’s penetration into the microbial cell and reaching the sensitive intracellular targets is largely influenced by the presence of lipopolysaccharide-lipoprotein complexes which are mainly found in the cell wall of Gram-negative microorganisms. Despite such impeding mechanism, some antibacterial agents deploy aqueous transmembrane channels called porins in the bacterial outer membrane to gain entry into Gram negative organisms. Moreover, both Gram positive and Gram-negative bacteria possess an outer membrane structure known as Peptidoglycan, which forms a rigid layer. However, Gram positive organisms have a very thick peptidoglycan layer (cross-linked with interpeptide bridges) and Gram-negative organisms have a very thin peptidoglycan layer. Numerous antibiotics, including penicillins, fosfomycin, cycloserine, bacitracin, cephalosporins, teicoplanin and vancomycin selectively inhibit peptidoglycan layer synthesis at different stages (Awad et al., 2012). On the other hand, antimicrobials such as ionophores affect the transport of cations through the cell membrane. The intracellular targets for antimicrobials include DNA replication and protein synthesis. Antibiotic agents such as chloramphenicol, puromycin, aminoglycosides, tetracyclines, fusidic acid, macrolides, lincosamides, mupirocin, streptogramins, and oxazolidinones interfere with the process of protein synthesis. Some antibiotics such as novobiocin, quinolones, diaminopyrimidines, nitroimidazoles, rifampicin and sulfonamides, inhibit DNA synthesis by targeting topoisomerases which are vital components for modulation of DNA supercoiling, an essential step in DNA replication (Drlica et al., 2008). However, microorganisms revealed an astonishing capability to adapt, evolve, and survive by developing resistance mechanisms to antimicrobial compounds; and antimicrobial resistance became a major global issue and significantly increased among bacteria, fungi and viruses which results in reduced efficacy of many clinically important and lifesaving antimicrobials (Seiffert et al., 2013) The development of antimicrobial resistance, which may be intrinsic or acquired occurring through mutation (Martinez & Baquero, 2018) or gene transfer from other species or strains(Hegstad et al., 2010; Palmer et al., 2010) is principally caused by alteration in the binding sites; modification of the metabolic pathways; alteration or inactivation of the drug; or decreased permeability (increased flux) of antimicrobial agents (Schmieder & Edwards, 2012). The growing rise of antimicrobial resistance inflicts a remarkable economic and social burden on the health care system globally.