Antibiotic resistance has become a global issue. The most significant risk is the acquisition of these mechanisms by pathogenic bacteria, which can have a severe clinical impact and pose a public health risk. This problem assumes that bacterial fitness is a constant phenomenon and should be approached from an evolutionary perspective to develop the most appropriate and effective strategies to contain the emergence of strains with pathogenic potential. Resistance mechanisms can be understood as adaptive processes to stressful conditions. This review examines the relevance of homeostatic regulatory mechanisms in antimicrobial resistance mechanisms. We focus on the interactions in the cellular physiology of pathogenic bacteria, particularly Gram-negative bacteria, and specifically Klebsiella pneumoniae. From a clinical research perspective, understanding these interactions is crucial for comprehensively understanding the phenomenon of resistance and developing more effective drugs and treatments to limit or attenuate bacterial sepsis, since the most conserved adjuvant phenomena in bacterial physiology has turned out to be more optimized and, therefore, more susceptible to alterations due to pharmacological action.