62 DECEMBER • WORLD AQUACULTURE • WWW.WAS.ORG parE), often coupled with efflux pump overexpression. Recently, plasmidmediated quinolone resistance has emerged, adding a transferable dimension to this problem. Tetracycline resistance is conferred by three major mechanisms: efflux pumps that expel the drug from the cell, ribosomal protection proteins that prevent binding, and enzymatic inactivation such as TetX-mediated hydroxylation. These processes enable near-complete crossresistance across tetracycline derivatives. Overall, bacterial resistance is a multifaceted phenomenon shaped by chromosomal mutations, mobile genetic elements, and adaptive enzyme systems. The rapid expansion of ESBLs, AmpC enzymes, and carbapenemases, combined with plasmid-mediated mechanisms in other drug classes, highlights the escalating threat of multidrug-resistant pathogens (Dowling et al., 2017). Favorable Impacts of Antibiotics in Aquaculture • Widely used as prophylactic and therapeutic agents to reduce the occurrence and spread of bacterial infections, especially in regions lacking alternative preventive measures. • Certain antibiotics, such as oxytetracycline and florfenicol, are also used as growth promoters, improving productivity of cultured species. • Utilized globally, including in Asia, Europe, Canada, and the USA, reflecting their recognized role in managing fish and shellfish health. Drawbacks of Antibiotics in Aquaculture • Often administered to entire populations, leading to overuse and misuse in many countries. • Dosages can be higher than in terrestrial farming, with contamination levels difficult to track. • Lack of proper training, education, and diagnostic facilities contributes to misuse. • Overuse has resulted in rejection of aquaculture products by export markets (e.g., EU, USA) due to residues of banned antibiotics. • Promotes the development of antibiotic resistance in aquatic environments and cultured species. • Human health risks arise from consuming fish treated with antibiotics. Alternatives to Antibiotics New antibioticfree measures are being developed to protect aquaculture species from pathogens. A holistic approach involving pathogen, host, and environment is most effective, with prevention as the main strategy. However, since infections cannot always be avoided, innovative control methods alongside rational antibiotic use are needed for sustainability (Figure 2). • A targeted approach to controlling pathogenic bacteria is the use of specific antibacterial agents instead of broad-spectrum ones. This method spares beneficial microbes and reduces the risk of resistance, since fewer bacteria are exposed. One such technique is bacteriophage therapy, which uses viruses that selectively infect and kill particular pathogens. • Another strategy to control pathogens is the use of short-chain fatty acids (SCFAs), which inhibit bacterial growth rather than kill them. SCFAs lower intestinal pH, promoting beneficial microbes like lactic acid bacteria while suppressing harmful bacteria. Their main limitation in aquaculture is leaching into water, requiring higher doses for effectiveness. • Virulence therapy focuses on disabling a pathogen’s ability to cause infection rather than killing it. This approach targets virulence factors, the traits essential for infection, by either disrupting their regulation (affecting multiple factors at once) or directly blocking a specific factor (Defoirdt et al., 2011). • Bacteriocins are small, ribosomally synthesized peptides that act as a sustainable alternative to antibiotics in aquaculture. They inhibit harmful pathogens while promoting beneficial gut bacteria, making them eco-friendly and safe for both fish and the environment. FIGURE 2. Approaches to curb antimicrobial application in aquaculture. Bondad-Reantaso et al. 2023. Overall, bacterial resistance is a multifaceted phenomenon shaped by chromosomal mutations, mobile genetic elements, and adaptive enzyme systems. The rapid expansion of ESBLs, AmpC enzymes, and carbapenemases, combined with plasmid-mediated mechanisms in other drug classes, highlights the escalating threat of multidrug-resistant pathogens.
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