1. IntroductionThe term “antibiotics” refers to the substances naturally produced by microorganisms such as actinomycetes, bacteria or fungi, which can inhibit the growth of other microorganisms and destroy their cells [1]. The introduction of antibiotics into clinical practice was the most incredible clinical breakthrough forward of the 20th century [2]. The introduction of the first antibiotics hugely impacted the treatment of various life-threatening bacterial infections and society by reducing morbidity and mortality [3]. Nonetheless, the most recent decade of the 20th century and the beginning of the 21st century have witnessed the emergence and spread of ABR in different pathogenic bacteria worldwide [4]. Continuous misuse of these valuable compounds has rapidly increased antimicrobial resistance in various pathogens that are effectively untreatable [2]. Thus, some organisms have become resistant to more than one antibiotic simultaneously and have been referred to as multidrug-resistant (MDR); some organisms are even resistant to all known antibiotics and are termed pan-drug resistant [5]. Furthermore, although initially developed to describe Mycobacterium tuberculosis strains resistant to first-line of treatment—“resistance to the first-line agents, isoniazid and rifampicin, to a fluoroquinolone and to at least one of the three-second-line parenteral drugs”, the term extremely drug resistance evolved to define any organism resistant to any standard antimicrobial treatment regimen [5]. Although modern scientific technologies have boosted humanity’s hope regarding developing new antibiotics, the current scenario shows few novel antibiotics under development. Simultaneously, antibiotic-resistant bacteria that endure antibiotic treatment are getting increasingly regular, making accessible antibiotics ineffectual. Hence, humanity is confronted by significant adverse public and environmental health impacts. This review examines the history of antibiotics and the ecological roles of antibiotics, and their resistance. In addition, this article adds information on the evolution of bacterial antibiotic resistance in different environments, including aquatic and terrestrial ecosystems, and modern tools used for its identification. Further, the review argues the ecotoxicological impact of antibiotic-resistant bacteria and public health concerns. Finally, it concludes with the possible strategies for addressing the challenge of antibiotic resistance. 2. History of Antibiotics Since the dawn of time, bacterial infections have had a predominant spot in human diseases [3] and caused death in humans. During ancient times (earlier 1640), Greeks and Indians used molds and other plants to treat wounds and infections, while farmers in Russia used warm soils to cure infected wounds. The doctors from Sumerian and Babylonian used beer soup mixed with turtle shells and snakeskins and a mixture of frog bile and sour milk to treat diseases. Likewise, the Sri Lankan army used oil cake (sweetmeat) as a desiccant and antibacterial agent. Despite the lack of a clear idea about the reason for these illnesses, there were consistent attempts to battle them.

Microorganisms exist in an unfathomably wide variety. The most prominent microbiologists, including Louis Pasteur (1822–1895) and Robert Koch (1843–1910), strongly believed that microbes must develop lethal weapons (“antibiosis”) to combat their rivals to thrive in a competitive environment, and that those that go through the competition have developed resistance to their opponents’ weapons. They reasoned that because the soil contains the greatest variety of microorganisms, this is where these mechanisms would be most effective. A scientist named Selman Waksman (1888–1973) coined the term “antibiotic” (meaning “against life”) in 1942. He explained that it is something microorganisms make at low concentrations to kill or inhibit the growth of other organisms. The term was used throughout the subsequent 20 years per the abovementioned specification. Although the term is still in use, it has expanded to include the many semi- and fully-synthetic “antibiotics” developed by the pharmaceutical industry.

Rudolph Emmerich and Oscar Löw, two German researchers, created the first antibiotic, pyocyanase, in the late 1890s. It was produced by growing the bacterium Pseudomonas aeruginosa in a lab and had questionable efficacy and safety when used to treat cholera and typhus. Later, Salvarsan, an arsenic-based medication discovered by Paul Ehrlich in 1909, was effective against the syphilis-causing bacterium Treponema pallidum. In other words, this finding paved the way for future research and development of antimicrobial drugs [6]. Penicillin, derived from the fungus Penicillium, was the first antibiotic supplied to doctors in the 1940s. As its development was preceded by years of study and observation during World War II, it is commonly referred to as “a child of the war” [1]. By the late 1940s and early 1950s, antibiotic chemotherapy was well tolerated in clinical medicine after the discovery of streptomycin and tetracycline from Actinomycetes. In addition to being efficient against the bacillus causing tuberculosis, these medicines were also effective against other pathogenic bacteria [3]. In this context, the filamentous actinomycetes (64%) were the primary source of most naturally occurring antibiotics, followed by the bacterial and fungal species (Table 1). On the other hand, synthetic derivatives are believed to be efficient against pathogenic microbes. First-generation cephalosporins, including parenteral medications like cephalothin (1964) and cefazolin (1970) and oral medications like cephalexin (1967), are the most effective against Gram-positive bacteria, methicillin-susceptible staphylococci, and non-enterococcus streptococci [3]. Unlike first-generation cephalosporins, which are effective against Gram-positive and Gram-negative bacteria, second-generation cephalosporins are more successful in the clinic against Gram-negative bacteria such as Hemophilus influenzae, Enterobacter aerogenes, and some Neisseria spp. [8,9,10]. Further, extended-spectrum cephalosporins such as cefpirome (1983), cefepime (1987), and cefaclidine (1989) have enhanced action against Enterobacter spp., Citrobacter freundii, Serratia marcescens, and severe P. aeruginosa infections [11,12,13]. Antibiotics gradually established themselves as life-saving medications. In the middle of the 20th century, a large increase in the number of novel antibiotic compounds developed for medical use was observed. Between the years 1935 and 1968, a total of 12 new classes were introduced. However, there was a significant decline in the number of new classes after this; between 1969 and 2003, merely two new classes were developed [14]. 3. Rise of Antimicrobial ResistanceThe term “antimicrobial resistance” (AMR) is used to describe the ability of bacteria and other microorganisms to resist the adverse effects of an antimicrobial to which they were formerly susceptible [15]. Antimicrobial resistance (AMR) was first noted in staphylococci, streptococci, and gonococci; penicillin-resistant S. aureus emerged in 1942 following the introduction of penicillin as a commercial antibiotic in 1941 [16]. However, in the early 1930s, Sulphonamide-resistant Streptococcus pyogenes appeared in human clinical settings. Later in the 1950s, the problem of multidrug-resistant enteric bacteria became evident [17]. Furthermore, methicillin, which is linked to penicillin and is a semi-synthetic antibiotic, was marketed in 1960 to treat S. aureus infections resistant to penicillin. Conversely, in the very same year, methicillin resistance emerged in S. aureus [18]. Since their introduction in the 1980s, fluoroquinolones have revolutionized the treatment of bacterial infections. Initially intended for use against Gram-negative bacteria, the emergence of fluoroquinolone resistance has shown that these medications have also been applied to combat Gram-positive infections, most notably among methicillin-resistant strains [19]. Furthermore, although Vancomycin has been on the market for 44 years, in 2002, clinical isolates of Vancomycin-resistant S. aureus (VRSA) emerged [20].A rise in deaths worldwide is attributed to bacteria resistant to multiple antibiotics. For example, there are over 63,000 annual deaths in the United States of America (USA) due to hospital-acquired bacterial infections [21]. Further, in 2019, the Centre for Disease Control (CDC) reported that over 2.8 million antibiotic-resistant infections occurred annually in the United States, leading to over 35,000 deaths [22]. The Indian Council of Medical Research (ICMR) released its annual report on antimicrobial resistance in 2020, which stated that the overall proportion of MRSA throughout the country had reached 42.1% in 2019, representing an increase of nearly 10% compared to the previous year [23]. According to the latest Global Antimicrobial Resistance and Use Surveillance System (GLASS) project report, data from South and Southeast Asian countries (such as India, Bangladesh, and Pakistan) reflect a considerable rise in antibiotic resistance levels. For instance, carbapenem-resistant Acinetobacter was found to be exceptionally high in Pakistan (66.9%), followed by India (59.4%). Similarly, the highest prevalence of carbapenem-resistant E. coli and carbapenem-resistant K. pneumonia was recorded in India (16.4% and 34.2%, respectively), followed by Bangladesh (9.2% and 11.2%) and Pakistan (6.2% and 11.3%) respectively. The other MDR pathogens, such as fluoroquinolone-resistant Salmonella sp. (80.3%) and MRSA (65%), were recorded as high in Pakistan [24]. According to the Antimicrobial Resistance Surveillance System (CARSS) and the China Antimicrobial Surveillance Network (CHINET), the antimicrobial resistance profiles of gram-negative bacilli are higher in China. There has been an increase in the incidence of carbapenem-resistant Klebsiella pneumoniae since 2005, and the prevalence of extended-spectrum-lactamases and antimicrobial resistance in Acinetobacter baumannii are both concerning. Furthermore, the incidence of methicillin-resistant Staphylococcus aureus and vancomycin-resistant Pseudomonas aeruginosa both declined between 2005 and 2017 [25]. According to a report published by the European Antimicrobial Resistance Surveillance Network (EARS-Net), between 2015 and 2019, there were shifts in the frequency of antimicrobial resistance throughout the European Union. These changes were based on the species of bacteria, with E. coli being the most common (44.2%), followed by S. aureus (20.6%), K. pneumoniae (11.3%), Enterococcus faecalis (6.8%), P. aeruginosa (5.6%), Streptococcus pneumoniae (5.3%), E. faecium (4.5%), and Acinetobacter spp. (1.7%) [22]. Due to limited resources and the difficulty of monitoring medicine supply systems within and outside their borders, many African countries struggle to protect their populations from unsafe and substandard/counterfeit medicines. Several African countries have not yet banned oral artemisinin monotherapies for uncomplicated malaria, for example. This is a major risk for developing resistance to artemisinin-based combination therapies [26]. In all African regions, S. aureus, Klebsiella sp., E. coli, and S. pneumoniae exhibited lower resistance to carbapenems and fluoroquinolones than other antibiotic combinations. In West Africa, Klebsiella spp. resistance to ciprofloxacin was greater than in other regions [27]. In conclusion, antimicrobial resistance has emerged as a severe threat to human health in the last decades, responsible for an estimated 700,000 annual deaths worldwide; is is anticipated to result in millions of deaths by 2050 if not adequately addressed [28]. 4. What Caused These Organisms in the Environment to Develop Resistance to Multiple Drugs?Bacteria are distinct in that they can acquire genes from the parent microorganism during division (vertical gene transfer) and from the larger community (horizontal gene transfer), first demonstrated for aminoglycoside resistance [29]. This horizontal gene transfer has been observed at every major taxonomic rank, even between bacteria and archaea. A strain that was once susceptible may acquire and transfer resistance to a new species or genus. Most antibacterial resistance genes are carried on plasmids (Table 2) and other mobile genetic elements (transposons, genomic islands, integrons, and gene cassettes) that can and do spread to bacteria of different genera and species [28]. Antibiotic resistance due to plasmids is widespread and includes resistance to many first-line treatments. Notable examples include fluoroquinolones, aminoglycosides, and cephalosporins, which are used extensively [30].Staphylococci isolated from the clinical setting frequently contain multiple plasmids, and this was the first instance of antibiotic-resistant bacteria posing a severe threat to hospital infection control [31]. Plasmids that encode resistance to sulfonamides and other antibiotics have been found in multidrug-resistant Salmonella enterica Typhimurium DT104 strains, suggesting that trimethoprim resistance is also encoded in these plasmids [32]. Similarly, vancomycin resistance genes have been found on large plasmids easily transferable in both E. faecalis and E. faecium [33]. Resistance plasmids in Enterobacteriaceae frequently contain narrow-spectrum beta-lactamases (such as penicillinases) and extended-spectrum beta-lactamases (ESBL). Multiple beta-lactamase genes, which can hydrolyse a wide variety of beta-lactam antibiotics, are frequently discovered to be located on the same plasmid [34]. Further, Enterobacter spp. harbor plasmids containing the intrinsic AmpC-lactamases gene, conferring resistance to ampicillin, amoxicillin-clavulanate, and first- and second-generation cephalosporins [35]. The first instance of plasmid-mediated quinolone resistance (PMQR) was discovered on a qnr plasmid in K. pneumoniae from a health centre. Subsequently, qnr was renamed qnrA and families of qnr genes (qnrB, qnrS, qnrC, and qnrD) due to differences in plasmid copy number and gene expression. Comparing the effects of carriage by highly antibiotic-susceptible laboratory strains frequently reveals the greatest variations [36]. The third group of plasmid fluoroquinolone-resistance genes are the oqxAB and qepA efflux systems, which code for transporters that can export fluoroquinolone molecules. Yet again, the carriage of these genes is associated with slight increases in the resistance to fluoroquinolones [37].

Table 2. Plasmid-borne genes for antibiotic resistance in different organisms.

Table 2. Plasmid-borne genes for antibiotic resistance in different organisms.

Antibiotic ResistancePlasmid-Borne GenesResistant OrganismsReferencesBeta-lactamsblaIMP encoding imipenem resistance;
blaVIM (Verona integron- encoded metallo-β-lactamases)P. aeruginosa[38,39]blaOXA encoding oxacillin resistanceS. aureus[40]blaNDM encoding metallo-β-lactamaseE. coli[41]blaNDM-1 gene; blaOXA-23A. baumannii[42]blaIMP-9, blaSIM-2, and blaVIM-2P. aeruginosa[42,43]blaNDM, blaIMP, blaIMP-27, blaVIM, and blaKPCEnterobacteriaceae[44,45]blaNDM-1E. coli[46]blaIMPMetagenome[39]blaOXA-23A. baumannii[42]blaTEM; blaSHV, blaOXAH. influenzae; E. coli; K. pneumoniae[47,48]blaTEMS. pneumoniae[49]PBP2aS. pneumoniae; E. coli[50,51]CTX-M, OXA-30E. coli[52]mecA,S. aureus[53]blaOXA-48Enterobacteriaceae[54]FluoroquinolonesqnrA, qnrB, qnrC, qnrD, qnrS, and aac(6′)-lb-crCampylobacter spp., Salmonella spp., and Shigella sp., K. pneumoniae, E. coli[55,56]gyrA E. coli[57,58]parC and parEE. coli; K. pneumoniae[57,59]NorC, NorA and MepAS. aureus[60]Rv1634Mycobacterium tuberculosis[61]MfpAMycobacterium[62]qnrS2Aeromonas[63,64]QepAE. coli[65]OqxABE. coli[66]parC and gyrAS. pneumoniae[67,68]SmeVWXS. maltophilia[69]SmqnrS. maltophilia[70]SmeDEFStenotrophomonas maltophilia[71]pqsAP. aeruginosa[72]glpD, ygfA, and yigBE. coli[73]GlycopeptidesvanA, vanB, vanC, vanD, vanE, vanG, vanL, vanM, and vanNEnterococci[74,75,76]vanRSHAXS. aureus[76]sarA[77]vanA and ermBEnterococci[78]Aminoglycosidesaac(3)-IVE. coli[79]Polymyxinsmcr-1E. coli[80]Tetracyclinestet genesStreptomyces[81]Tn916B. subtilis[82] Tet38S. aureus[83]Lipopetides pitAS. aureus[84]RifampicinpurB and purMS. aureus[85]CephalosporinsblaCTX-M, blaCMYKluyvera ascorbata; Kluyvera georgiana[86]blaCTX-M-1 and blaCMY-2E. coli[87]VancomycinvanA, vanB, vanH, vanR, vanS, vanW, vanX, vanY, and vanZS. aureus[88]Multidrug resistance (MDR)acrBE. coli[89]SGI1S. enterica[90]blaNDM-1P. aeruginosa[91]Like plasmids, resistance transposons are mobile genetic elements that carry resistance genes. For example, many Gram-negative bacteria, especially Enterobacteriaceae, contain the transposable element Tn5 (encodes resistance to aminoglycosides like kanamycin and neomycin) and Tn10 (encodes resistance to tetracycline). Other gene clusters include Tn3, encoding resistance to numerous β-lactam antibiotics, including ampicillin, and Tn21, encoding resistance to streptomycin, spectinomycin, and sulphonamides [30]. A recent study investigated Tn7-like transposons in Enterobacterales isolates from food animals. The study found that 54.9% of the isolates were multidrug-resistant, and high resistance rates were observed against streptomycin and trimethoprim-sulfamethoxazole [92].Resistance integrons are conserved sequences that, through site-specific recombination, can acquire gene cassettes that can transport drug-resistance genes [93]. For instance, K. pneumonia and K. oxytoca isolates resistant to gentamicin and cotrimoxazole were observed in patients with nosocomial infections. It was found that a significant number of these isolates carried integrons that contained inserted regions of foreign DNA encoding antibiotic resistance genes [94]. Four known classes of resistance integrons to date. Class I and II integrons contain multiple gene cassettes that code for antimicrobial resistance mechanisms like dihydroflavonol-4-reductase (dfr), broad-spectrum-lactamase (bsl), lipoprotein signal peptidase, quaternary ammonium compound (QAC) enzymes, sul1 (sulfonamide), and aminoglycoside-modifying enzymes (AMEs) [93]. In addition, these integrons have been observed in Gram-negative organisms such as Acinetobacter, Aeromonas, Alcaligenes, Burkholderia, Campylobacter, Citrobacter, E. coli Pseudomonas, Klebsiella, and Salmonella sp. [95,96,97]. Class III integrons were first discovered in S. marcescens transferred by Tn402 in Japan in 1993; however, they are not as active as other classes. However, the IncQ plasmid from E. coli has recently been found to contain a class III integron encoding blaGES-1 (an ESBL-encoding gene) [98,99,100]. In addition, gene cassettes that confer resistance to fosfomycin and chloramphenicol have been identified in class IV integrons [101]. However, current research is limited to class I integron and Gram-negative bacteria. Class I integron on Gram-positive microorganisms, along with classes II, III and IV, has barely been touched, making such concerns unnoticed about antibiotic resistance determinants. Further, the complex origin of antibiotic resistance still hinges on several factors. These include antibiotic overuse and abuse, inaccurate diagnosis, inappropriate antibiotic medicating, loss of responsiveness in patients, patients self-medicating, poor healthcare settings, lack of personal hygiene, and pervasive agricultural use [102,103]. 5. Mechanisms of Antibiotic ResistanceThe development of antibiotic resistance is a natural ecological phenomenon and the product of billions of years of evolution. However, much attention has been focused on antibiotic resistance in pathogenic organisms encountered in hospitalized patients and bacteria responsible for adverse health effects [104]. In addition, microbes in pristine environments, such as caves and permafrost, have been studied and found to develop resistance in the absence of human interference. Antibiotics are used for a wide variety of bacterial infections in humans and animals. This promotes the generation of resistance or “immunity” genes in the producer organisms and the selection of resistance in environmental species. The presence of resistance in the natural environment may be a natural occurrence’ this reservoir of resistance genes can be mobilized and transferred into human pathogens, worse the situation [105,106,107]. The presence of identical genes in both environmental and human bacteria demonstrates the movement of resistance genes from different environmental reservoirs, including aquatic and terrestrial environments, into human pathogens and vice versa. Furthermore, environmental microorganisms already have genes encoding resistance to antibiotics before they are widely used commercially [108,109].The development of antibiotic resistance has brought to light a plethora of diverse and intricate mechanisms responsible for the genesis and propagation of antibiotic resistance among bacteria of the same species or even among bacteria of different species [110]. Important resistance mechanisms shown in Figure 1 include (i) antibiotic exclusion by the cell membrane, (ii) antibiotic modification and/or deactivation within the cell, (iii) reduced sensitivity of the cellular target, (iv) antibiotic exclusion from the cell, and (v) intracellular sequestration [111]. These multiple processes mediate antibiotic resistance enabling bacteria to become resistant to all currently available antibiotics. For instance, three biochemical pathways can lead to fluoroquinolone resistance; these pathways can exist in the same bacteria at the same time with increased expression and, often, increased resistance levels such as (i) overexpression of efflux pumps that effectively remove the drug from the cell, (ii) mutations in genes that encode the target site of fluoroquinolones (DNA gyrase and topoisomerase IV), and (iii) protection of the fluoroquinolone site of action by a protein named Qnr [112]. The most common resistance mechanism in Gram-negative bacteria is the production of beta-lactamases; in Gram-positive organisms, resistance is typically achieved by alteration of the target site, i.e., penicillin-binding proteins (PBPs) [112]. One of the unique mechanisms of antibiotic resistance is the efflux pumps system, which pumps antibiotics and other toxins out of the cell. This mechanism is crucial in bacteria becoming resistant to the antibiotic. On the other hand, Gram-negative bacteria acquire tetracycline resistance via efflux pump systems, specifically the tet efflux pumps, which export tetracyclines from cells through proton exchange [113]. Other MDR efflux pumps that extrude tetracycline are AcrAB-TolC and MexAB-OprM, found in Enterobacteriaceae and P. aeruginosa [114]. Finally, resistance to trimethoprim is caused by alterations in metabolic pathways, such as the increased production of dihydrofolate reductase, an enzyme that lacks the binding site for trimethoprim [115], and dihydropteroate synthase. This enzyme mediates resistance to sulfonamides [116]. Table 3 explains the different mechanisms is mediating antibiotic resistance. 7. Antibiotic-Resistant Bacteria and Human Health ConcernsAntibiotic resistance or drug resistance is a worldwide public health crisis requiring immediate action. In 2019, antimicrobial resistance was linked to 4.95 million deaths, 1.27 million of which were attributed to drug-resistant illnesses alone. Without concerted action, this number might exceed ten million by 2050, costing more than USD 100 trillion [253]. In recent decades, many pathogenic bacteria have evolved into multi-drug resistant (MDR) bacteria. For instance, the US Centre for Disease Control and Prevention (CDC) released a list of the top public threats in 2015, which included drug-resistant diseases and classified them as Urgent, Serious, or concerning threats (Table 4). Four urgent threats include carbapenem-resistant Enterobacteriaceae and Acinetobacter, drug-resistant N. gonorrhoeae and Clostridium difficile, causing numerous deaths annually in the US and other countries. Serious infections include those indicated in Table 4, such as methicillin-resistant S. aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) infections and extremely drug-resistant tuberculosis (XDR-TB). Other members of this category include S. pneumoniae, which accounts for most bacterial pneumonia and meningitis worldwide, and Acinetobacter, Campylobacter, fluconazole-resistant Candida, Enterobacteriaceae (Pseudomonas aeruginosa, Salmonella (both typhi and non-typhi) generating a beta-lactamase that has extensive activity against most penicillins and cephalosporins. It is estimated that this group is responsible for around 22,500 deaths annually in the United States. In addition, the presence of streptococci resistant to erythromycin and clindamycin is viewed as “of concern” [16]. While these concerns focus more on human consumption of antibiotics, it should be noted that these problematic organisms could also originate from animal sources—directly through contact with infected animals or indirectly through the consumption of contaminated animal products. For example, hospitalized pets have been recognized as significant reservoirs and sources of carbapenem-resistant bacteria, including Acinetobacter spp. [254], implying a possible direct transmission from these animals to humans. These carbapenem-resistant bacteria have also been identified in food animals [255,256], meaning that indirect transmission to humans could occur through the consumption of these animals as a protein source. 8. Strategies for Addressing the Challenge of Antibiotic ResistanceThe challenge posed by antibiotic-resistant bacteria can be categorized into five primary intervention strategies within the human and veterinary sectors. In the first place, infection prevention and control principles continue to be the cornerstone in the fight against the spread of ABR [22]. Second, vaccinations are a critical tool for preventing infections and decreasing the demand for antibiotics. Although new vaccine initiatives are being developed for S. aureus, E. coli, and others, vaccines are only available for one of the six leading pathogens (S. pneumoniae) [257]. Third, reducing exposure to antibiotics for purposes other than treating human disease is an essential potential risk-reduction strategy. An increase in ABR in humans has been linked to the widespread use of antibiotics in agriculture, though the exact cause-and-effect relationship is still up for debate [258]. Intensive farming imposes stress on food animals, forcing farmers to use antibiotics to treat their animals [259]. However, treating individual sick animals is challenging; hence, providing antibiotics to all animals on a farm prophylactically through their feed and water helps reduce the disease burden and improves animal health. This is not without consequences, as ABR is favoured under such conditions. Combating this phenomenon would require the observation of stringent biosecurity measures [260] and the use of alternatives to antimicrobials to treat sick animals [261]. Fourth, antibiotics should not be used to treat viral infections unless necessary. For antimicrobial use can be reduced or stopped when necessary, it is critical to establish mechanisms that facilitate rapid and accurate diagnosis of disease by clinicians [262]. Finally, it is essential to continue investing in the pipeline for developing new antibiotics and providing access to second-line antibiotics in areas that do not have widespread access [263]. It is an urgent priority to identify strategies that can reduce the burden of bacterial ABR across a wide range of settings or specifically tailored to the available resources and the leading pathogen–drug combinations in a particular setting.

The environmental dimension of ABR remains the least addressed component in the fight against this global ill. This is partly because the environment presents a more complex scenario involving numerous stressors than humans and animals. Nevertheless, wastewater treatment plants have been recognized as hotspots for the dissemination of ABR in the environment. Therefore, improving the quality of the effluents from these plants would reduce the discharge of polluted waters containing antimicrobial-resistant pathogens and ARGs into receiving water bodies. This is, however, challenging for areas in low- and middle-income countries where such facilities are unavailable. Nevertheless, greater sensitization and the provision of mobile toilets could prevent open defecation and pollution of the environment.

Although these strategies have been presented separately, it must be noted that for effective, sustainable solutions to be achieved in the fight against ABR, firm collaborations and communication must be established between actors in the One Health triad—humans, animals, and the environment.

9. Conclusions

Antibiotic resistance remains a significant challenge threatening human, animal and environmental health. Although ABR has increased over the years due to the indiscriminate use of antibiotics in human and veterinary settings, ABR is also shown to be a natural process, with resistance genes discovered in pristine environments with little or no human interference. Furthermore, although less studied, the environmental dimension of ABMR constitutes a significant reservoir as a source of ABR through horizontal and vertical transfer, with plasmids and other mobile genetic elements playing a crucial role in this process. Within the environment, other less-considered factors like heavy metals and pesticides also play an important role in selection pressure, inducing resistance in previously susceptible environmental organisms. Furthermore, wastewater treatment plants remain major contributors of ARB and ARGs in the environment. Given the broad distribution of ABR, solutions aiming to curb this ill should be multifacet, involving antimicrobial stewardship in humans and animals, prevention of environmental pollution and promoting the discovery of new antibiotics, among others.