# The Invisible Threat of Antibiotic Resistance in Food
## 2 Antibiotics and Their Effects on Bacterial Resistance
### Antibiotic Resistance and Tolerance: Adaptation Strategies  
Bacteria have the capacity to adapt to their environment and develop mechanisms to survive and proliferate in the presence of antibiotics [99]. \"_Adaptation is simply the process of evolution by natural selection_\" [100]. Adaptation involves the progressive modification of microorganisms in a stressful environment to increase their tolerance [101]. Antibiotics are a significant source of stress for bacteria, prompting them to activate protective responses. Bacterial genome plasticity is imperative for the adaptation and response to environmental threats, including the presence of antibiotics [102]. An enhanced comprehension of bacterial stress responses and evolution indicates that, under certain conditions, the capacity of bacteria to withstand antibiotic therapy, either by transiently tolerating antibiotics or by evolving resistance, necessitates specific biochemical processes [103]. It is evident that several mechanisms can lead to resistance, and these have been the subject of detailed investigation [104]. These molecular mechanisms are categorized into classic and novel groups of resistance. Classic mechanisms encompass (i) antibiotic target modification or protection, (ii) antibiotic inactivation, (iii) increased efflux, or (iv) reduced uptake of antibiotics. Among the newly emerging antibiotic resistance mechanisms (v) the inactivation of bacterial metabolic enzymes, (vi) siderophore receptor mutation, (vii) formation of wall off antibiotics, and (viii) amplification of transposon in tandem array should be mentioned [105; 106; 107; 108]. Moreover, a significant proportion of bacteria possess an inherent resistance to a wide range of antibiotics, including many commonly prescribed medications. Acquired resistance, on the other hand, is developed through gene mutations or via external genetic acquisition from nearby resistant organisms through horizontal gene transfer (HGT) [102]. Intrinsic resistance refers to the innate ability of species to resist a particular antibiotic agent due to their inherent structural and/or functional features (it is not transferable) [109]. It can be found in the genome of bacterial species and is independent of previous antibiotic exposure (antibiotic selective pressure) and HGT [110; 111]. It is a stable, heritable trait specific to species or larger taxa. It may be linked to, e.g., the absence of a receptor for the antibiotic, a lack of affinity of the drug for the bacterial target, cell wall impermeability, or the presence of drug-degrading enzymes [112]. Intrinsic resistance includes, for example, the natural resistance of Gram-negative bacteria to vancomycin due to their cell wall structure (due to their large size and high molecular weight, these substances are unable to penetrate the outer membrane) [113]. The phenomenon of acquired resistance is achieved by the transfer of the genetic material conferring resistance. It is the result of mutations in the genetic material of the microorganism, or the transfer of the genetic material itself, which provides resistance via plasmids, bacteriophages, transposons, integrins, or other mobile genetic elements (MGEs), and is usually by conjugation, less often by transduction or transformation [1; 114; 115; 116]. These MGEs can be horizontally transferred between different genera, even between pathogenic species. Acquired resistance develops as a result of selection pressure on the bacterial population [117]. Antibiotic resistance is a direct consequence of genetic alterations that are inherited by daughter cells; in contrast, antibiotic tolerance is an alternative strategy that enables survival in the presence of antibiotic doses that exceed MIC. The term antibiotic tolerance is frequently employed in scientific literature to denote the phenomenon of non-heritable antibiotic resistance. In the review by [PERSON] and [PERSON] [118], the term was defined as the reduced efficacy of antibiotics in the absence of genotypic resistance.