The origin of antibiotic resistance is an area of active study. There is evidence that naturally occurring antibiotic resistance is common.[1] The genes that confer this resistance are known as the environmental resistome.[1] These genes may be transferred from non-disease-causing bacteria to those that do cause disease, leading to clinically significant antibiotic resistance.[1]
In 1952 an experiment conducted by Joshua and Esther Lederberg showed that penicillin-resistant bacteria existed before penicillin treatment.[2] While experimenting at the University of Wisconsin-Madison, Joshua Lederberg and his graduate student Norton Zinder also demonstrated preexistent bacterial resistance to streptomycin.[3] In 1962, the presence of penicillinase was detected in dormant Bacillus licheniformis endospores, revived from dried soil on the roots of plants, preserved since 1689 in the British Museum.[4][5][6] Six strains of Clostridium, found in the bowels of William Braine and John Hartnell (members of Franklin Expedition) showed resistance to cefoxitin and clindamycin.[7]
It was suggested that penicillinase may have emerged as a defense mechanism for the bacteria in their habitats, as in the case of penicillinase-rich Staphylococcus aureus, living with penicillin-producing Trichophyton. This, however, was deemed to be circumstantial.[6] Search for a penicillinase ancestor has focused on the class of proteins that must be a priori capable of specific combination with penicillin.[8] The resistance to cefoxitin and clindamycin in turn was speculatively attributed to Braine's and Hartnell's contact with microorganisms that naturally produce them or to random mutation in the chromosomes of Clostridium strains.[7] Nonetheless there is an evidence that heavy metals and some pollutants may select for antibiotic-resistant bacteria, generating a constant source of them in small numbers.[9]