Tuesday, March 16, 2010

The Microbiology of Antibiotic Resistance, Part 2: Bacterial Reproduction and Mechanisms of Resistance

Bacteria populate some of the most extreme and diverse environments in the world – from hydrothermal vents, located thousands of feet below sea level, to deep within the human body. This ability to cope with and adapt to ever changing environments in order to survive can be partially attributed to favorable evolutionary traits, which allow bacteria to quickly mutate and acclimate to new a environmental stressor, such as the presence of an antibiotic. These mechanisms of resistance are either natural (inherent) or acquired resistances (1).
With a natural resistance, bacteria may be resistant to the environmental stressor due to inherent structural or chemical characteristics. For example, a Gram-negative bacteria’s double cell wall acts as a permeability barrier against some antibiotics, preventing the drug’s uptake by the bacteria and thus eliminating its ability to affect the cell.
Acquired resistance can be further classified into vertical and horizontal gene transfer with vertical transfer temporally preceding horizontal gene transfer. One out of every 108 - 109 chromosomal replications will result in an unlinked point mutation that leads to antibiotic resistance. With the fast growth and high frequency of bacterial replication, it does not take long for resistance to appear in a bacterial population. Once resistance genes develop through mutations, they are transferred to all the bacteria’s progeny during DNA replication. In a stressed environment, with the presence of antibiotics for example, the wild type bacterial genome will not be able to survive and this spontaneous mutation, imparting resistance, will allow the mutant antibiotic-resistant bacteria and its progeny to grow, flourish and overtake the entire bacterial population (2).
Once a bacterium has acquired a favorable spontaneous mutation, it can also pass the mutation onto other non-progeny bacteria through horizontal gene transfer, which involves the lateral transfer of genetic material between individual bacteria of the same of different species. This transfer usually involves the acquisition and maintenance of the supplementary genetic information on accessory DNA pieces termed plasmids.
These plasmids exist separately from the main bacterial chromosome; carry their own unique genes, sometimes as many as 300; and are able to duplicate themselves independently. Each bacterial cell may have as many as 1000 copies of a single plasmid and are able to have several unique plasmids concurrently. The benefits of this come with the information that plasmids can carry, which allow bacteria to perform new functions and create new products that are not coded in their chromosomal genetics. Some of these new traits will allow bacteria to survive in extreme environments, while others confer important functions to bacteria, such as antibiotic resistance. Many times, two plasmids, frequently ones that carry genes for antibiotic resistance, are able to combine to form one large plasmid or exchange pieces of their DNA to create more diversity on a single plasmid. Thus, a single bacterium can acquire multiple antibiotic resistance genes from one plasmid.
Through the exchange and uptake of different plasmids, one bacterium can gain the ability to survive through a wide variety of environmental stresses. Plasmid exchange occurs in bacteria through horizontal gene transfer, even between distantly related bacteria. When one bacterial cell acquires antibiotic resistance, it can quickly transfer this resistance to several other species of bacteria through one of three common methods: conjuction, the transfer of genetic material, usually a plasmid, through cell-to-cell contact, usually by pili; transformation, the introduction, uptake and expression of foreign genetic material; and transduction the transfer of DNA by a bacteriophage (bacterial virus) (3).

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