There are several unique aspects of microbial genetics that largely account for the great genotypic and phenotypic diversity, the ability to cause disease, and the propensity to develop resistance to virtually any antibiotic observed in bacteria. Bacteria have a simple genetic organization relative to eukaryotic organisms. They are haploid, usually possessing a single chromosome and therefore a single copy of each gene. This is in contrast to eukaryotic cells (such as human cells), which are diploid, meaning they have a pair of each chromosome and therefore have two copies of each gene. In diploid cells, one copy of a gene (allele) may be expressed as a protein (i.e., be dominant), whereas another allele may not be expressed (i.e., be recessive). In haploid cells, any gene that has acquired a mutation will result in a cell synthesizing either a mutant protein or no protein at all depending on the type of mutation.
A mutation is a change in the base sequence of DNA that can result in the insertion of a different amino acid or stop codon into a protein and the appearance of an altered phenotype. Mutations result from three types of molecular changes:
The first type is the base substitution. This occurs when one base is inserted in place of another. It takes place at the time of DNA replication, either because the DNA polymerase makes an error or because a mutagen alters the hydrogen bonding of the base being used as a template in such a manner that the wrong base is inserted. When the base substitution results in a codon that simply causes a different amino acid to be inserted, the mutation is called a missense mutation; when the base substitution generates a termination codon that stops protein synthesis prematurely, the mutation is called a nonsense mutation. Nonsense mutations almost always destroy protein function.
The second type of mutation is the frameshift mutation. This occurs when one or more base pairs are added or deleted, which shifts the reading frame on the ribosome and results in incorporation of the wrong amino acids “downstream” from the mutation and in the production of an inactive protein.
The third type of mutation occurs when transposons or insertion sequences are integrated into the DNA. These newly inserted pieces of DNA can cause profound changes in the genes into which they insert and in adjacent genes.
Mutations can be caused by chemicals, radiation, or viruses. Chemicals act in several different ways.
Some, such as nitrous acid and alkylating agents, alter the existing base so that it forms a hydrogen bond preferentially with the wrong base (e.g., adenine would no longer pair with thymine but with cytosine).
Some chemicals, such as 5-bromouracil, are base analogues, since they resemble normal bases. Because the bromine atom has an atomic radius similar to that ...