# The Invisible Threat of Antibiotic Resistance in Food
## 2 Antibiotics and Their Effects on Bacterial Resistance
### Antibiotic Resistance and Tolerance: Adaptation Strategies
In the presence of antibiotics, tolerant cells are unable to replicate, thereby maintaining MIC at its original level. These tolerant cells are killed at a slower rate than more sensitive cells, leading to an increased Minimum Duration for Killing (MDK) of the population [119]. The term \"population-wide tolerance\" is employed to denote all cells within a population that exhibit the tolerant phenotype. In contrast, \"tolerance restricted to a subpopulation of cells\" is referred to as \"persistence\" or \"heterotolerance\" [119]. In the context of persistent infections, it was observed that a population or subpopulation of bacteria may exhibit resistance to conventional antibiotics, potentially in a state of non-replicating or metabolically altered growth [118]. In such cases, bacteria adapt to the stresses imposed by the host environment by entering a different physiological state, such as a non-replicating or slowly replicating growth rate, or a small colony variant (SCV) phenotype. The size and composition of the persister subpopulation in bacterial communities are largely controlled by stress signaling pathways, such as the general stress response or the SOS response, in conjunction with the second messenger (p)ppGpp, which is almost always involved in persister formation [120]. Antibiotics may contribute to the occurrence of ARGs through multiple actions, including the exertion of selective stress to allow the accumulation of resistant strains, the promotion of the horizontal transfer of ARGs, and the facilitation of resistance mutations [121]. Stress-induced mutations, otherwise referred to as adaptive mutagenesis, were demonstrated to play a significant role in the progress of antibiotic resistance. Stress conditions caused by exposure to antibiotics are known to induce genotoxic stress in bacterial cells [122]. Stress proteins, also referred to as universal stress proteins (USPs), exist across a wide range of species and play a pivotal role in enabling organisms to withstand challenging environments [123]. Antibiotics require active cells to kill; however, persisters are a small subpopulation of cells that enter a dormant state and cease independent division. In the context of a bactericidal antibiotic treatment, regular cells perish, whereas persisters survive, thereby facilitating their tolerance [122; 124]. The model developed by [PERSON] and [PERSON] [125] demonstrates that cell death is seldom attributable to antibiotic levels that exceed the maximum physiological limit. Instead, survival is constrained by the inability to modify gene expression rapidly enough to transition to a less susceptible physiological state. Furthermore, bacteria often overexpress stress response genes, even at the cost of reduced growth, thereby conferring enhanced protection against further antibiotic exposure. This strategy is in contrast to those employed in different nutrient environments, in which bacteria allocate resources to maximize growth rate. This underscores a pivotal trade-off between the cellular capacity for growth and the ability to survive antibiotic exposure. Given that both resistance and tolerance contribute significantly to the failure of antibiotic treatments, understanding the mechanisms of their evolution becomes imperative [126].