Antibiotics in Food Chain: The Consequences for Antibiotic Resistance

Abstract

Antibiotics have been used as essential therapeutics for nearly 100 years and, increasingly, as a preventive agent in the agricultural and animal industry. Continuous use and misuse of antibiotics have provoked the development of antibiotic resistant bacteria that progressively increased mortality from multidrug-resistant bacterial infections, thereby posing a tremendous threat to public health. The goal of our review is to advance the understanding of mechanisms of dissemination and the development of antibiotic resistance genes in the context of nutrition and related clinical, agricultural, veterinary, and environmental settings. We conclude with an overview of alternative strategies, including probiotics, essential oils, vaccines, and antibodies, as primary or adjunct preventive antimicrobial measures or therapies against multidrug-resistant bacterial infections. The solution for antibiotic resistance will require comprehensive and incessant efforts of policymakers in agriculture along with the development of alternative therapeutics by experts in diverse fields of microbiology, biochemistry, clinical research, genetic, and computational engineering.

Keywords: horizontal evolution; microbiome; quorum-sensing; resistome.

Figure 1

Timeline of antibiotic discovery and its onset of resistance. The antibiotic paradigm emerges out of the followed discovery of penicillin. Between the 1960s and the 1980s there was a surge in the discovery of antibiotics, but this development declined between the 1980s and the 1990s. The identification of new antibiotic classes by pharmaceutical companies has stagnated since 1987 and coincided with progressively increased antibiotic resistance and mortality related to antibiotic-resistant infections.

Figure 2

Mechanisms of horizontal and vertical transmission in bacteria for the development of antibiotic resistance. The left panel shows the horizontal transmission of an antibiotic resistant gene (ARG, red line indicated by a red arrow) by the three main mechanisms: conjugation, transformation, and transduction. Conjugation involves transfer of the ARG from a donor bacterium to a recipient by direct contact and plays a crucial role in dissemination of antibiotic resistance. Transformation involves uptake of the free DNA with the ARG from the environment. Transduction is a virus-mediated gene transfer by bacteriophages. The right panel shows the vertical evolution carried out by replication of bacteria containing the ARG.

Figure 3

Schematics of the major route of antibiotic resistance genes (ARG, a red inserted line) dissemination in environment. The diagram indicates the contribution of human communities to the production of antibiotics and their uses in hospitals, farms, and households. Generated antibiotic waste is released onto sewage, hence contaminating water, soil, and environment. Bacteria develop ARG mutations as a result of such exposure to antibiotics in the environment, and in human and animal hosts. ARG-containing bacteria spread in humans and animals through direct infections, food, or environment. The arrows indicate the putative transmission paths of entry of antibiotics and ARG.

Figure 4

Schematic illustration of faecal microbiota transplantation (FMT) procedure. The left panel of the above figure depicts sample preparation where stool is harvested from healthy donors, processed via different stages such filtration, slurry preparation followed by cold storage in stool bank. The right panel illustrates the FMT procedure, where processed faecal microbiota of healthy donor stored in stool bank is either delivered via rectal route or oral route to the diseased patients (recipient) to provide a healthy microbiome community.

Figure 5

Schematic principle of action by nano-antibiotic therapies including nitric oxide (NO) releasing nanoparticles and nanoparticles in combination with antibiotics. The various nano-antibiotics (nAbts, purple shape) and NO-releasing nanoparticles (green circles) act via two components: metal ions (Ag⁺, Cu²⁺, Zn²⁺) (yellow particle in the centre) and a releasing component such as NO with or without antibiotics. Both components increase production of reactive oxygen species (ROS) in the bacterium as well as in the host immune cells (e.g., macrophages, neutrophils). Left panel, in the bacterium, NO inhibits catalase activity, which leads to rise in levels of hydrogen peroxide. In the presence of transition metals of nanoparticles catalyse conversions of hydrogen peroxide to a hydroxyl radical (HO•). Hydroxyl radical is one of many ROS and RNS responsible for oxidative and nitrosative stress and death of bacteria. ROS leads to disruption of cell membrane, interruption of transmembrane electron transport, oxidation of cellular components, protein and DNA damage. These actions disrupt structural and functional integrity of bacteria.