Milk and meat are some of the most important products derived from animal husbandry. Thus, it is highly pertinent to improve the well-being of food-producing animals, such as cows, goats, ducks, fish and fowl for quality milk, meat and egg production, respectively. Breaches in the various guidelines relating to animal welfare may lead to several diseases, and hence, a decline in animal products . Consequently, milk and meat may become inedible and therefore be discarded, resulting in wastage, failure to meet consumer demands and a decline in the supply of meat, milk, their derivatives and other related products. Other losses associated with animal husbandry are the high cost of treating infected animals, the premature culling of diseased animals and the spread of infections to other animals and humans (zoonotic transmission) which all contribute significantly to economic losses . In addition, microbial products, toxins and enzymes produced by pathogenic bacteria species such as S. aureus that are present in milk can cause food-related diseases in humans. More so, the remnants of S. aureus in cells can become a source of recurrent infections .

Food-producing animals are the main reservoirs for most foodborne pathogens, such as the Campylobacter species, the Salmonella enterica non-Typhi serotypes, the shiga toxin-producing Escherichia coli, S. aureus, Bacillus cereus, Listeria monocytogenes and Clostridium botulinum . Moreover, foodborne pathogens may arise from different sources which include the environment (water from various sources, animal dung disposal sites and wildlife), as well as human-related animal handling (slaughtering and processing practices, and storage procedures) . The ability of these pathogens to produce toxins that cause illness or even death in both humans and animals amplifies their public health significance. Infections caused by these foodborne pathogens are usually treated with standard antibiotics. However, the indiscriminate use of these antibiotics in animals may exert pressure on the environment, and in response, the disease-causing microorganisms may develop resistant mechanisms against the antibiotics .

There are probable reservoirs of resistance wherever antibiotics are used, including in humans and animals, on farms, as well as in environments, such as hospitals, water sources, soil, wildlife, and many other ecological niches. This resistance may also be attributed to pollution from sewage, pharmaceutical and industrial waste, and runoff from farm manure (Figure 1) . Bacteria and their genetic materials (DNA and/or plasmids) may readily be transmitted between humans, animals and the environment. AMR is therefore a menace and is defined by complex interactions between distinct microbial populations that influence human, animal and environmental health . Hence, actions taken (or not) to combat AMR in one industry may have an impact on other industries . It is thus imperative to combat this global challenge by utilizing coordinated cross-sectoral strategies, such as One Health, that take into consideration the complexity and ecological nature of the problem.

Nanotechnology refers to the system of synthesizing materials of different sizes and shapes at the nanoscale (10⁻⁹ one-billionth of a meter) level by utilizing matter . These particles with significantly reduced sizes (about 1 to 100 nanometres) possess physical and chemical properties that differ drastically from large-scale materials made up of the same component. This technology has since evolved into a diverse field of applied science and technology and is projected to have an impact on practically every aspect of daily living. Over the last decade, research in this field has expanded, and many types of nanoscale materials are now available in different countries .

2. Emergence of Multidrug Resistance (MDR) Pathogens in the Food Chain

A leading public health issue in recent decades has been the growth of multi-drug resistant (MDR) bacteria. The prevalence of these pathogens in animal-derived products, including milk and meat, has risen considerably and their potential to evolve new features, notably MDR, is significant . The upsurge in MDR bacteria has hitherto remained undisclosed to the animal food-service sector because there has previously been virtually no communication of their occurrence in animal-based products. However, more recently, new exceptions, such as mobile colistin-resistant (mcr) strains and New Delhi metallo-β-lactamase-1 (NDM-1)-producing variants in food-producing animals, have been surfacing as discrete pools of colistin and β-lactam resistance, along with the alternative carbapenem antibiotic-resistant strain . The use of antibiotics has long been linked to the emergence of drug resistance . When an antibiotic is ingested, it kills vulnerable bacterial cells, while the resistant ones continue to proliferate and become the dominant strains . This provides opportunities for the transfer of resistant genes to their offspring . Given that the food supply chain is an ecological niche made up of diverse biological points in which significant amounts of drugs are utilized and scores of bacteria coexist, food-producing animals, seafood, meat and milk are regarded as significant pools for the proliferation of antimicrobial-resistant bacteria . Antibiotic resistance may occur in one of two ways. Firstly, it can occur as intrinsic resistance, in that an existing natural composition in the bacterial species provides that specific species with the potential to resist the action of an antibiotic ^[1]. During their developmental stages, bacterial cells amass genetic flaws in their chromosomes and/or plasmids and pass down the same to their daughter cells through vertical gene transfer (VGT), thus accounting for natural or inherent resistance ^[1]. The other mechanism, termed “acquired resistance”, involves the transfer of genetic materials between and within bacterial species. This mechanism involves the lateral transfer of the genetic materials in a process called horizontal gene transfer (HGT). These codes are carried on or within selfish genetic elements, including transposons .

Use of Antibiotics in Animal Agriculture, Their Mode of Action and Resistance Mechanisms

Antibiotics are routinely utilized in animal production to support the health and development of the animals. Producers and consumers as a whole gain certain financial advantages from this strategy. For a very long time, antibiotics have been thought of as the first line of defence against bacterial infections in animal husbandry. They are still essential medical drugs that must be handled with caution when treating sick animals, thus ethical livestock production does not have to completely forego their use. Antibiotics can be categorized according to their modes of action, which include the inhibition of cell wall synthesis, the suppression of nucleic acid synthesis, the repression of ribosome function, the inhibition of cell membrane function, and the inhibition of folate metabolism (Table 1). However, there are certain issues connected to the use of antibiotics in animal agriculture. Given that the antibiotics used are identical to or substitutes for the antibiotics used in human treatment procedures, there has been great worry that repeatedly exposing these animals to low dosages of antibiotics adds considerably to antimicrobial resistance. Livestock alone consumes 50–80% of all antibiotics produced in the majority of the developed countries . Animals are frequently given less antibiotics than are used for therapeutic purposes when using them as a growth promoter. Due to the frequent exposure of bacteria to sub-lethal doses of antibiotics and the favourable conditions for the selection and maintenance of resistance features, this approach is more likely to exert significant pressure on the emergence of antimicrobial resistance mechanisms (Table 1).

3. Annals of One Health Antimicrobial Resistance

Antibiotic resistance is a growing issue of severe public health concern worldwide and is now regarded as a critical One Health issue. Based on a concise historical record, two accounts of some of the antimicrobial resistance issues that have resulted from the use of the same antibiotic classes in humans and animals, as well as the associated complications with competing interests, are described. The first scenario, which focuses on third-generation cephalosporins, demonstrates One Health concerns with an antibiotic that is primarily used for therapeutic purposes in animals and is also used prophylactically in some key conditions. The second scenario is colistin, an older type of antibacterial agent that has long been utilized in animals for medicinal, preventive and growth-promotion objectives, but has only lately gained prominence in the human health arena.

3.1. Third-Generation Cephalosporins

Broad-spectrum beta-lactam antibiotics, known as third-generation cephalosporins, are routinely utilized in humans and animals. Cefotaxime, ceftriaxone and other members of this group are employed to treat a wide range of infections in humans, including urinary tract, abdominal, lung, and bloodstream infections caused by E. coli, Klebsiella pneumoniae, and other bacteria, as well as infections caused by Neisseria gonorrhoeae . This class of antibiotics has been designated as “critically essential” for human health because of its critical role in the treatment of numerous bacterial infections, in which resistance has become a serious issue . Extended-spectrum beta-lactamases (ESBLs) and AmpC beta-lactamases are responsible for resistance to third-generation cephalosporins. ESBL genes are easily spread by plasmids, transposons and other genetic elements . Originally thought to be chromosomally associated, AmpC beta-lactamases have also been found on plasmids and demonstrated to have been propagated through horizontal transfers throughout Enterobacteriaceae . Unfortunately, resistance to third-generation cephalosporins is frequent in E. coli and K. pneumoniae, both emanating from serious human infections in many countries and forcing clinicians to rely more heavily on the few remaining antimicrobial classes, such as carbapenems. According to a study by the World Health Organization (WHO) , as opposed to susceptibility to infections, patients with third-generation cephalosporin-resistant E. coli infections showed a two-fold increase in all-cause deaths, bacterium-attributable mortality and 30-day mortality. Salmonella species have also been found to harbour resistance, which is mediated mostly by the CMY-2 AmpC beta-lactamase genes that are usually remotely-hosted with genes encoding resistance to other antimicrobial classes, such as tetracyclines, aminoglycosides and sulfonamides . Although much of the proliferation of E. coli with ESBL and other β-lactamases is assumed to be clonal, the relevant genes have been found in a range of bacteria from humans, animals and the environment . From a One Health perspective, third-generation cephalosporins are favourably considered to be critically essential for both human and animal health (Table 2). As a result, third-generation cephalosporins are widely used either as therapeutic or prophylactic agents, which facilitates the spreading of resistance from animals to humans (Table 1). Another family of antibiotics, the fluoroquinolones, has been used in similar approaches and has thus led to resistance to these antimicrobial agents. Following the mass treatment of chicken flocks, resistance to key antimicrobials has evolved among Campylobacter jejuni isolates .

3.2. Colistin

Colistin is an antibiotic that belongs to the family polymyxin, which has been utilized in human and animal care for more than five decades . Polymyxins, which are toxic to the neurons and nephrons of humans, were hitherto primarily used as colistimethate sodium by inhalation in humans for topical applications and in the nursing of cystic fibrosis patients . Colistin is becoming more popular as a last resort for treating multi-drug-resistant Gram-negative infections, such as carbapenem-resistant Pseudomonas aeruginosa, Acinetobacter baumannii, K. pneumoniae, and E. coli, primarily in intensive care units in several countries . Most often, colistin is administered orally to herds of pigs, poultry, and in certain circumstances, calves, for its therapeutic or prophylactic benefits in food-producing animals . Colistin is also used as a growth promoter in animals in several countries . Owing to technical problems in phenotypic susceptibility testing, compulsory checks for colistin resistance in Salmonella and E. coli from animals and some food products began in Europe as recently as 2014 . A study reported that among the 162 colistin-resistant E. coli isolates from chicken, MDR was found in 91.4% of the cases . In the recent past, acquired colistin resistance was assumed to be limited to chromosomal mutations and was basically non-transferable . However, in 2015, findings from a study in China revealed the presence of a colistin resistance gene, mcr-1, in E. coli isolates from animals, food, and human bloodstream infections . Colistin differs from third-generation cephalosporins in some critical One Health aspects of antibiotic resistance. These are associated with the accounts and style of colistin usage in humans and animals, as well as with the successive establishment of resistance to the polymyxin group of antibiotics, which were most likely triggered by the massive amounts of colistin used in animals rather than in humans . In addition, the use of Avoparcin in animals has been linked to the choice and proliferation of vancomycin-resistant Enterococcus (VRE) species and glycopeptide-resistant genes in enterococci from animals, food, humans and the environment .