Question

Cellular and molecular mechanism of action of antimicrobial agent

Answer 1

Infectious diseases caused by bacterial pathogens represent a serious public health concern. Antimicrobial agents such as anti-bacterial drugs are often indicated for chemotherapy of bacterial infections in clinical medicine. Thus, it is important to study the biological mechanisms that confer bacterial pathogenesis and virulence. Under selective evolutionary pressure when in the presence of antimicrobial agents, bacterial variants evolve mechanisms to survive in the presence of these inhibitory agents. Drug resistant bacteria that are selected with a single drug are also frequently multi-drug resistant against multiple structurally different drugs, thus confounding the chemotherapeutic efficacy of infectious disease caused by such pathogenic variants. There are several major classes of mechanisms for bacterial resistance to antimicrobial agents: (a) enzymatic inactivation of the drug results from the metabolic degradation of the drug into a form that is rendered ineffective in inhibiting bacterial growth; (b) alteration of the drug target results in the inability of the drug to bind to its biological target, thus rendering the drug unable to kill the bacteria. Bacterial cellular drug targets may include the protein synthesis apparatus, nucleic acid synthesis enzymes, cell wall synthesis machinery, and metabolite pathway enzymes; (c) drug permeability reduction mechanisms prevent cellular entry of drug into the inside of the bacterial cell; and (d) active efflux of drugs from bacteria results in the intracellular dilution of drugs, making the extruded drugs unavailable for their inhibitory action. Unfortunately, these drug and multi-drug resistance mechanisms are poorly understood at the molecular level, impeding our advances towards identifying new targets for possible inhibition of clinical multi-drug resistances; this prevents chemotherapeutic usefulness. Understanding how these bacterial resistance mechanisms work from the standpoint of molecular physiology and biochemistry will identify new targets for potential inhibition of multi-drug resistance and thus restore clinical utility of chemotherapy of infectious disease caused by serious bacterial pathogens.