is the ability of amicroorganismto withstand the effects of antibiotics. It is a specific type of drug resistance. Antibiotic resistance evolves vianatural selectionacting upon randommutation, but it can also be engineered by applyingan evolutionary stress on a population. Once such ageneis generated, bacteria can thentransfer the genetic information in a horizontal fashion (between individuals) by plasmidexchange. If a bacterium carries several resistance genes, it is called
. The term
is sometimes used toexplicitly encompass organisms other than bacteria.Antibiotic resistance can also be introduced artificially into a microorganism throughtransformationprotocols. This can aid in implanting artificial genes into themicroorganism. If the resistance gene is linked with the gene to be implanted, theantibiotic can be used to kill off organisms that lack the new gene.
Schematic representation of how antibiotic resistance evolves via natural selection. Thetop section represents a population of bacteria before exposure to an antibiotic. Themiddle section shows the population directly after exposure, the phase in which selectiontook place. The last section shows the distribution of resistance in a new generation of bacteria. The legend indicates the resistance levels of individuals.Antibiotic resistance can be a result of horizontal gene transfer
, and also of unlinked point mutations in the pathogengenomeand a rate of about 1 in 10
per chromosomalreplication. The antibiotic action against the pathogen can be seen as an environmental pressure; those bacteria which have a mutation allowing them to survive will live on toreproduce. They will then pass this trait to their offspring, which will result in a fullyresistant colony.Several studies have demonstrated that patterns of antibiotic usage greatly affect thenumber of resistant organisms which develop
resistance. Other factors contributing towards resistanceinclude incorrect diagnosis, unnecessary prescriptions, improper use of antibiotics by patients, the impregnation of household items and children's toys with low levels of
antibiotics, and the administration of antibiotics by mouth in livestock for growth promotion.Researchers have recently demonstrated the bacterial proteinLexAmay play a key rolein the acquisition of bacterial mutations.
insome penicillin-resistant bacteria through the production of β-lactamases.2.Alteration of target site: e.g. alteration of PBP —the binding target site of penicillins—inMRSAand other penicillin-resistant bacteria.3.Alteration of metabolic pathway: e.g. somesulfonamide-resistant bacteria do notrequire para-aminobenzoic acid(PABA), an important precursor for the synthesisof folic acidandnucleic acidsin bacteria inhibited by sulfonamides. Instead, likemammalian cells, they turn to utilizing preformed folic acid.4.Reduced drug accumulation: by decreasing drug permeabilityand/or increasingactiveefflux(pumping out) of the drugs across the cell surface.
5.There are three known mechanisms of fluoroquinolone resistance. Some types of effluxpumps can act to decrease intracellular quinolone concentration. In gram-negative bacteria, plasmid-mediated resistance genes produce proteins that can bind toDNA gyrase,protecting it from the action of quinolones. Finally,mutations at key sites in DNA gyrase or Topoisomerase IVcan decrease their binding affinity to quinolones, decreasing the drug's effectiveness.
) is oneof the major resistant pathogens. Found on themucous membranesand theskinof arounda third of the population, it is extremely adaptable to antibiotic pressure. It was the first bacterium in which penicillinresistance was found—in 1947, just four years after thedrug started being mass-produced.Methicillinwas then the antibiotic of choice, but hassince been replaced byoxacillindue to significant kidney toxicity. MRSA (methicillin-resistant
) was first detected in Britain in 1961 and is now "quitecommon" in hospitals. MRSA was responsible for 37% of fatal cases of blood poisoningin theUK in 1999, up from 4% in 1991. Half of all
infections in theUSareresistant to penicillin, methicillin,tetracyclineanderythromycin.This leftvancomycinas the only effective agent available at the time. However, strainswith intermediate (4-8 ug/ml) levels of resistance, termed GISA (glycopeptide