The ultimate source of all alleles is the process of mutation. These changes may occur in either the endogenote or exogenote of a cell. Genes transmitted from one cell to another may increase in frequency in a microbial population. Genes for drug resistance that are found on the endogenote provide the cell with chromosomal resistance.
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Those found on plasmids provide extrachromosomal resistance. For example, chromosomal resistance to streptomycin occurs with a frequency of about 10 –10 and primarily centers on the cell’s ability to modify ribosomal structure. Drugs such s streptomycin is unable to attach to these modified ribosomes and interfere with protein synthesis.
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Other chromosomal mutations exist which enable bacteria to resist the effects of kanamycin, erythromycin, and tetracycline. Extrachromosomal resistance is usually associated with the production of enzymes that are able to destroy such drugs as the penicillins, cephalosporins, and chloramphenicol.
Also found on a plasmid are the genes that code for the production of the enzyme responsible for blocking the entrance of erythromycin. Gram-negative pathogens such as E. coli and Pseudomonas aeruginosa have between 60 to 90 percent of their resistance genes located on plasmids.
Since many of these R factors (like F factor) are self-replicating and self-transmitting, they are able to be spread very quickly by conjugation (and transformation) through a population of bacteria.
The likelihood of this transmission is greatly increased when Gram-negative bacteria are found in highly concentrated populations and subjected to the artificial selective pressure of antibiotics.
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These circumstances are typically associated with the normal intestinal flora of humans and many domesticated animals. Hospitals and military organizations using large amounts of antibiotics in the treatment of Gram-negative infections have also demonstrated a high incidence of drug resistance.
In one study, farm workers were found to harbor an abnormally large percentage of antibiotic-resistant, Gram-negative bacteria in their fecal material.
These farmers regularly supplemented their pig feed with antibiotics. This same heavy selective pressure is placed on populations of Gram-negative pathogens in hospital environments.
As more patients are treated with larger dose of broad spectrum antibiotics to control already resistant microbes, the frequency of resistance in pathogens such as Proteus, Serratia, Pseudomonas, and Enterobacter has drastically increased.
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The fact that patients and staff alike are confined to the hospital environment only serves to increase the possibility of exchanging drug-resistant bacteria and increases the severity of the problem.
Furthermore, increased resistance may also increase the virulence of pathogens and make the treatment of Gram- negative infections more complicated. Gram-positive pathogens such as Staphylococcus aureus have also experienced a dramatic increase in drug resistance.
However, conjugation has not been observed, and a third method of plasmid transfer is needed to explain the high incidence of drug resistance in this group. The transduction process relies on viruses to carry the genes for drug resistance from one bacterium to other of the same species.