From the mechanistic point of view three basic principles of microbial resistance to drugs are known: inactivation of the drug, alteration of the target, and reduced drug accumulation at the target site. However, several variations on these themes are known.

The phenomenon of bacterial resistance to antibiotics was already known by the pioneers of the era of antibiotics, like Paul Ehrlich, who coined the term “selective toxicity” as the basic principle of antimicrobial therapeutics, as well as Gerhard Domagk, the inventor of the sulfonamide drugs, and Sir Alexander Fleming, the discoverer of the penicillins. When penicillin G was introduced into clinical practice in 1944, as many as 5% of the isolates of Staphylococcus aureus were resistant to penicillin, while 5 years later the percentage was 50%.

That bacterial resistance predates the era of clinical use of antibiotics by several hundred millions of years is the recent result of genomic sequence data...