Genetic mutations resistance

Bacteria can develop resistance to antimicrobial agents as a result of mutational changes in the chromosome or via the acquisition of genetic material (resistance genes carried on plasmids or transposons or the recombination of foreign DNA into the chromosome) (Fig. 2). 

Bacteria can obtain the various types of resistance mechanisms described previously by undergoing modifications in their genetic constitution. Many bacteria simply inherit their resistance genes from their forerunners. In addition, genetic mutations can occur that can confer a new trait. For example, it has been estimated that bacteria undergo spontaneous mutation at a frequency of approximately 1 in 10 cells. These mutations can confer resistant traits to the subsequent progeny. Mutations are believed... 

Resistance—In bacteria, the acquisition of genetic mutations that render the bacteria invulnerable to the action of antibiotics. 

Bacteria have been shown to present either acquired or intrinsic acquired resistance to the quinolone agents. Acquired resistance occurs due to genetic mutations affecting the structure of the A subunit of DNA gyrase as well as membrane permeation of the agents. The mechanism of intrinsic resistance has not yet been defined. It is expected that resistant DNA gyrase or altered drug permeation or both will be involved (30). 

Several genetic mutations have been described in the insuhn receptor and are associated with insulin resistance. Type A insuhn resistance refers to the clinical syndrome of acanthosis nigricans, virilization in women, polycystic ovaries, and hyperinsulinemia. Leprechaunism is a pediatric syndrome with specific facial features and severe insulin resistance due to a defect in the insuhn receptor gene. Lipoatrophic diabetes probably results from postreceptor defects in insulin signaling. 

The complete genetic code is shown in Figure 24.16. We can make several observations about the genetic code. First, methionine and tryptophan are the only amino acids that have a single codon. All others have at least two codons, and serine and leucine have six codons each. The genetic code is also somewhat mutation-resistant. For those amino acids that have multiple codons the first two bases are... 

Figure 18.9 Apoptosis resistance is a hallmark of cancer. Multiple genetic lesions results In an Increased apoptotic threshold that accompanies the cancerous phenotype. The relative resistance of cells to apoptosis Is Indicated by the thickness of the arrow and the key genes involved In setting the apoptotic threshold are shown. The function of these genes can be affected by either genetic mutations (such as loss of heterozygosity, LOH) or direct inhibition of their function by cellular Inhibitors (such as Bcl-2, lAP, or heath shock (HSP) proteins). The ultimate outcome is the inability of cancer cells to undergo apoptosis despite exposure to potent cell death triggers (such as In case of therapeutic inten/ention with chemo- or radiation therapy).

The evolution of different species is the result of genetic mutations, which occur in organisms as primitive as bacteria. Bacteria can exchange genes. When grown in a culture medium, they reproduce every 20 or 30 min. Mutations enhance their survival in the face of a harmful environment, such as an environment containing antibiotics. Mutations result in the reproduction of bacteria resistant to the effects of antibiotics. The antibiotic-resistant bacteria survive and reproduce, creating a new strain of bacteria. 

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