, 1987), which was different from what was observed in C. albicans with fluconazole (Andes et al., 2006). A possible explanation for the difference in the best dosing strategy in the different systems was proposed by Andes et al. (2006) to be the differences in modes of action on the target organisms. Aminoglycoside antimicrobials have cidal activities
against the bacteria tested while fluconazole is a fungistatic agent for C. albicans. The cidal activity of selleck screening library the aminoglycoside antimicrobials can effectively reduce the population size of the pathogens and thus reduce the supply of beneficial mutations. Under this type of selection, genetic drift may play a more important role because of the smaller population sizes, leading to the higher frequency of loss of rare beneficial mutations; thus exposure to a cidal agent may result in a more buy Galunisertib homogeneous population structure containing few drug-resistant mutants. However, a fungistatic agent may not effectively reduce the size of the population significantly to prevent the emergence of rare beneficial mutations, possibly leading to a more heterogeneous population containing multiple beneficial mutants. Thus, depending on the mode of action of the antimicrobial agent, different population dynamics may emerge. Additional studies with C. albicans using
fungicidal agents will help to shed additional insight on the effects of the mode of action of the drug on the population dynamics during drug exposure.
The fitness effect associated with a resistance mutation plays a key role in determining whether the resistant genotype can survive drift and whether it will become dominant in the population (Andersson, 2003; Andersson & Hughes, 2010). It is expected that if drug-resistant mutations carry a fitness cost in the absence of drug, the proportions of the drug-resistant phenotypes will decrease and may even be eliminated from the population when the drug is removed and further compensatory evolution is absent. This type of trade-off in the relative fitness between different environments is commonly out observed (Johanson et al., 1996; Schrag & Perrot, 1996; Schrag et al., 1997; Bjorkman et al., 1998, 1999; Sandegren et al., 2008). Several scenarios have been used to describe such differences in fitness effects in different environmental conditions (Elena & Lenski, 2003). The first scenario is antagonistic pleiotropy (AP), which describes mutations that are beneficial in one condition but are deleterious in another environment. The second is mutation accumulation (MA), in which neutral mutations that accumulated in one environment are deleterious in another condition. The third scenario is independent adaptation (IA), which describes mutations with beneficial effects in one environment but neutral in another.