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Resistance Mutation

A resistance mutation is a point mutations in virus genes that allow the virus to become resistant to treatment with a particular antiviral drug. The term was first used in in the management of HIV, the first virus in which genome sequencing was routinely used to look for drug resistance. Resistance mutation is now studied in bacteriology and parasitology. Resistance mutations can also be found in bacteria and infer resistance to anti-biotic drugs. Once a mutation has occurred it can be transferred horizontally to other members of the species via plasmids or transposons. This can result in a pathogen being immune to known treatments.

Origin of Resistance

Resistance mutations arise through evolution of the viral and bacterial genomes. Anti viral and antibiotic drugs create a selection pressure to evolve resistance. Both viral and bacterial have a quick replication times resulting in them occurring mutations at a high rate. If a mutation interferes with the mechanism of the drug it will infer resistance to the drug. A resistance mutation normally reduces the fitness of the organism this is known as the biological cost of resistance. However in an environment where the drug is present only the drug resistant organism survive. The organism can then thrive and grow as all competition without the resistance mutation has been eliminated.

Types of Mutations There are three main types of genes that when mutated might introduce resistance: Genes involved in synthesis of antibiotic target, this can result in the antibiotic not recognizing it's target. Genes involved in access of the antibiotic to its target, this can involve transport to the target or failing to activate the antibiotic. Finally genes causing protection of target form the drug, these include antibiotic modifying enzymes. Resistance can arise from a single gene mutation, Independent mutation. More often a variety of mutations are needed to invoke resistance this is known as cooperative mutation.

Prevention Drug cocktails are seeing increased use to combat pathogens developing resistance. Drug cocktails are treatments using several different anti-biotic or anti-viral drugs administered at the same time. This results in the organism not being able to evolve resistance to the drugs. If a mutation evolves which occurs resistance to one drug it will still be killed by another. This has seen effective use in treating HIV.