Development of microbial resistance to antimicrobial agents requires alterations in the microbe's cell physiology and structure. Antimicrobial resistance is defined as the loss of susceptibility to an extent that the drug is no longer effective for clinical use against an organism. Resistance can be mediated by the environment or the microorganism itself (Figure 1).
Environmentally-mediated antimicrobial resistance is affected by the environment's chemical and physical properties such as pH, anaerobic conditions, cation concentrations (calcium, magnesium), and thymine-thymidine content (available metabolites and nutrients).
Microorganism-mediated antimicrobial resistance is due to genetically-encoded traits of the microorganism and can be divided into intrinsic or acquired. Intrinsic resistance is considered to be a natural and inherited property with high predictability. Once the identity of the organism is known, the aspects of its anti-microbial resistance are also recognized. On the other hand, acquired resistance results from a change in the organism's genetic makeup. This trait is associated with only some strains of an organism's group but not the others. It is also an unpredictable trait and necessitates the development of laboratory methods to detect it. Microorganism-mediated antimicrobial resistance is acquired by gene change or exchange such as genetic mutations, acquisition of genes from other organisms via gene transfer mechanisms, or a combination of mutational and gene transfer events. Some common pathways bacteria use to effect antimicrobial resistance include: enzymatic degradation or modification of the antimicrobial agent, decreased uptake or accumulation of the antimicrobial agent, altered antimicrobial target, circumvention of consequences of antimicrobial actions, uncoupling of antimicrobial agent-target interaction, or any combination of these mechanisms.