Mechanisms of Resistance

Antibiotics, whether made in the laboratory or in nature by other microbes, are designed to hinder metabolic processes such as cell wall synthesis, protein synthesis, or transcription, among others. If humans are to prosper against microbial disease, it is necessary to understand how and why bacteria are able to mount their clever defenses. Aided with the knowledge of the genetics and mechanisms of resistance, scientists can discover new ways to combat the resistant bacteria.

The phenomenon of antibiotic resistance in some cases is innate to the microbe. For instance, penicillin directly interferes with the synthesis of bacterial cell walls. Therefore, it is useless against many other microbes such as fungi, viruses, wall-less bacteria like Mycoplasma (which causes "walking pneumonia"), and even many Gram negative bacteria whose outer membrane prevents penicillin from penetrating them. Other bacteria change their "genetic programs," which allows them to circumvent the antibiotic effect. These changes in the genetic programs can be in the form of chromosomal mutations, acquisition of R (resistance) plasmids, or through transposition of "pathogenicity islands."

An example of a chromosomal mutation is the increasing number of cases of penicillin-resistant Neisseria gonorrhae. This bacterium mutated the gene coding for a porin protein in its outer membrane, thereby halting the transport of penicillin into the cell. This is also termed "vertical evolution," meaning that the spread occurs through bacterial population growth. The most common method by which antibiotic resistance is acquired is through the conjugation transfer of R plasmids, also termed "horizontal evolution." In this method the bacteria need not multiply to spread their plasmid. Instead the plasmid is moved during conjugation. These plasmids often code for resistance to several antibiotics at once.

The third method is transfer due to transposable elements on either side of a "pathogenicity island," which is group of genes that appear on the DNA

Gram negative bacteria that do not take up Gram stain, due to membrane structure plasmids small rings of DNA found in many bacteria pathogenicity ability to cause disease conjugation a type of DNA exchange between bacteria

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