The original source of a number of resistance genes has been traced to antibiotic-producing bacteria. Antibiotic resistance resulting from mutation to alter the target site for the antibiotic usually involves only one or two amino acid changes in the protein. Since humans don't have that antiporter system, we are intrinsically resistant to tetracyclines. The transfer of penicillinases between cells can occur by conjugation. The diagram below was used to illustrate a number of points about sulfonamide resistance.
Sulfonamides block the folate synthase by a process of non-competitive inhibition.
The organism can overcome this blockade by increasing production of para-aminobenzoic acid. Humans are intrinsically resistant to sulfonamides. Transformation requires the pre-existence of a resistance gene. Transformation is a laboratory curiosity easily shown with Pseudomonas, but is not thought to be a clinically relevant process by which resistance occurs. The replica plate experiment is rationalized based on transformation.