Evolution and Antibiotic Resistance

The discovery of antibiotics to fight infectious diseases has revolutionized society. Common causes of mortality from infections such as syphilis and meningitis have declined dramatically since the introductions of antibiotics. Antibiotics have also enabled the development of advanced medical techniques such as cancer chemotherapy. Furthermore, antibiotics are heavily utilized in agriculture as growth enhancers.

Bacteria, however, show remarkable adaptability in the face of antibiotic therapeutics. Following the introduction of a new antibiotic, bacterial strains resistant to the new drug can be detected within a few years. There is a growing need to better understand how bacteria respond and evolve in the face of antibiotic treatments.

Bacteria become resistance to antibiotics via two major ways: spontaneous mutation and transfer of genetic material. Transfer of genetic material can occur through three specific mechanisms; transduction, transformation, and conjugation. Transduction is the transfer of genetic information between bacteria through bacteriophages. Some bacteria can uptake foreign DNA without bacteriophages; this is known as transformation. Conjugation is the transfer of functional DNA known as plasmids.

Bacteria may gain antibiotic resistance by induction of endogenous processes in the absence of horizontal gene transfer. Generally, decreased DNA fidelity in bacteria can be advantageous as it leads to the generation of mutants adapted to thrive in stressful environments. Further investigation into endogenous processes bacteria activate may reveal additional mechanisms by which antibiotic resistance develops in the absence of horizontal gene transfer.

The development of antibiotics to combat infectious diseases stands as one of the most significant advancements in medicine and public health. Since the discovery of Penicillin in 1929, our mechanistic understanding of antibiotics has centered on the chemical inhibition of essential bacterial proteins. To date, this drug-target model has been a success. However, the efficacy of these antibiotics is continually undermined by the preferential selection of resistance mutants, an unfortunate result of antibiotic use. As a consequence, we are always breeding new strains of antibiotic resistant bacteria.

Even in the absence of genetic changes, antibiotic tolerance mechanisms allow subpopulations of bacteria to withstand repeated treatments of lethal antibiotics, leading, in some cases to persistent and chronic infections.

These antibiotic-evasion tactics are particularly worrisome in light of the declining number of new antimicrobials in the development pipeline. There is a growing appreciation for the role those microbial environments, metabolic stresses within and metabolic influences between microbes, play in the defense strategies utilized by bacteria, to deal with antibiotics.

While the direct targets of most antibiotics