NTU Undergraduates' research April 2014 - Biosciences | Seite 6

Targeting evolution in the fight against antibiotic resistance
Christopher Patton
Abstract
The increasing frequency of pathogens acquiring resistance and the level of resistance seen in
pathogens to current antibiotics presents an ever increasing threat to global public health (Levy & Marshall,
2004). In the past the conventional method of combatting antibiotic resistance was to alter the structure of
antibiotics and develop new more effective semi-synthetic antibiotics but this method was limited and we have
now entered an age where very few new antibiotics are being developed (Norrby et al., 2005). This lack of
development of new antibiotics means that emergence of new antibiotic resistant strains of bacteria are
becoming increasingly more problematic to treat. In an attempt to try and manage the evolution of antibiotic
resistance practices have been advocated that regulate how antibiotics are used in treatments but these have not
proven to be effective enough (Read et al., 2011).
This review asks the question: are there more effective ways in which to reduce the evolution of
antibiotic resistance? This question was answered by reviewing information on the mechanisms that are
involved in the evolution of antibiotic resistance and identifying potential ways to target these evolutionary
mechanisms. Reducing antibiotic use also reduces the evolution of antibiotic resistance by removing the
selection pressure they apply on bacterial populations. Therefore alternatives to antibiotics were also looked at.
Conjugation was identified as the predominant evolutionary mechanism by which bacteria acquire
resistance and relaxase inhibitors were identified as the most promising way to inhibit conjugation in a broad
range of plasmids. Antibiotics were found to cause a transient increase in the rate of the evolution as well as
cause an increase in the frequency of ‘hypervariable’ strains in a population due to second order selection.
Inhibition of the SOS response via inhibition of RecA protein was identified as a potential way to reduce the
effects of antibiotics on evolution rates. Various alternative therapies were identified and evaluated. The most
promising out of these that had already been shown to be effective at reducing antibiotic use was the use of
vaccinations. These findings show that more effective ways of targeting and reducing the evolution of antibiotic
resistance are available and that efforts to promote their development and introduction into current clinical
practices should to be made.