## 1 Introduction  
Amid the ongoing antimicrobial resistance (AMR) crisis, bacterial survival strategies in response to antibiotic pressure have become a topic of increasing scientific and clinical relevance. Historically, research has focused primarily on genetic mechanisms of resistance, such as mutations in molecular targets, the overexpression of efflux pumps, enzymatic modifications, and horizontal gene transfer [1, 2, 3]. In recent years, however, a new dimension of bacterial resistance has emerged--more dynamic and plastic--centered on the ability of pathogens to profoundly reconfigure their metabolic architecture to adapt to hostile conditions, including those imposed by sublethal antibiotic exposure. This phenomenon, known as \"metabolic rewiring,\" involves the reorganization of major metabolic pathways to reduce drug susceptibility, optimize energy production under stress, and modulate the expression of virulence and persistence genes [4; 5]. Selective pressure from antibiotics acts not only as a mutagenic force but also as a biochemical stimulus capable of inducing reversible alterations in redox balance, energy homeostasis, and macromolecular biosynthesis [6]. An increasing number of studies have shown that metabolic adaptation can affect antibiotic susceptibility even in the absence of canonical genetic changes, through the modulation of pathways such as glycolysis, the tricarboxylic acid (TCA) cycle, the glyoxylate shunt, lipid metabolism, and oxidative stress responses [7; 8]. This phenotypic flexibility enables bacteria to enter a state of low metabolic activity--known as persistence--in which antibiotic efficacy is drastically diminished [9]. An additional layer of complexity arises from the interaction between bacterial metabolism and the host environment, including immune signals, nutrients, commensal microbiota, and temperate phages. In particular, the ability of bacteria to integrate environmental cues via quorum sensing (QS) systems and central metabolic pathways enables a coordinated adaptive response that often determines the outcome of infection [10]. Despite the emerging significance of these phenomena, current reviews in the literature tend to address metabolic rewiring only partially, often focusing on individual pathways or collateral effects of antibiotic pressure, without integrating their systemic, evolutionary, and clinical implications. In particular, there is a lack of critical syntheses that connect metabolic alterations to the molecular mechanisms of tolerance and the subsequent emergence of stable resistance mutations, as highlighted by recent experimental and conceptual models. This review aims to fill that gap by offering a critical and systemic overview of metabolic reprogramming in bacterial pathogens in response to antibiotic pressure. Specifically, it seeks to:  
* analyze the main metabolic circuits involved in rewiring induced by antibiotics from different classes (\(\beta\)-lactams, aminoglycos, quinolones, glycoptides, etc. );
* describe the interplay between molecular signaling, redox responses, and mutagenesis;
* discuss the evolutionary and therapeutic implications of these mechanisms, clearly distinguishing between metabolic plasticity and acquired genetic resistance; and
* propose an integrated conceptual framework for identifying novel metabolic targets, with a view toward metabolite-guided antibiotic therapy. 2 Key Concepts: Operational Definition of Metabolic Rewiring and Distinction from Genetic Resistance  
The concept of metabolic rewiring refers to the set of functional and dynamic restructuring processes of an organism's metabolic networks in response to environmental perturbations, including antibiotic pressure [11].