Antibiotics are classified on the basis of their chemical structure. As a result, members of a given class are closely related molecules, sharing the same mode of action and therefore prone to cross-resistance. This is why resistance must be approached in terms of classes, not isolated molecules. Bacteria have developed four main resistance mechanisms: (i) modification of the target, resulting in reduced affinity of the molecule for its target; (ii) production of an enzyme that inactivates the antibiotic; (iii) impermeability; and (iv) extrusion of antibiotics out of cells by energy-dependent pumps.
The bacterial genome is made up of the chromosome and accessory mobile genetic elements. The chromosome contains the genetic information necessary for the life of the cell, while, as their name suggests, the genetic elements carry genes that are dispensable, although they may provide important advantages for host survival, such as antibiotic resistance. Resistance can be endogenous, secondary to mutations in chromosomal structural or regulatory genes, and is generally not infectious from bacterium to bacterium. Conversely, exogenous resistance is due to the horizontal transfer of genetic information between bacteria. There are three levels of resistance dissemination, depending on the vector: bacterial (clonal dissemination), replicon (plasmid epidemic) or gene (transposon epidemic). These various levels, which are responsible for the extraordinary increase in resistance, are not only infectious but also exponential, as each is associated with DNA replication. The acquisition of resistance corresponds to a gain in function and is therefore generally associated with a biological cost; resistant derivatives have a lower degree of fitness than the parental strain. The biological cost determines the stability and reversibility of resistance. Compensatory evolution can occur, reducing the biological cost and stabilizing resistant bacteria in the natural population. As the spread of resistance is closely associated with the extent of selection pressure, the only hope is to delay this spread. This leaves us with just one recommendation: antibiotics must be used with care.
