A picture of the population dynamics PD98059 order (the changing genotypic landscape within the microbial population in the presence of antibiotics) will provide valuable insights into the aforementioned questions and contribute to the elucidation of the fundamental principles underlying how microbial pathogens evolve resistance to antimicrobial agents. Among human fungal pathogens, Candida spp. is recognized as a major challenge in public health, causing potentially life-threatening invasive infections in immunocompromised patients. Candida

spp. is the fourth most common cause of blood stream infections with a mortality rate approaching 50% in US hospitals (Zaoutis et al., 2005; Pfaller & Diekema, 2007). The species distribution among clinical Candida isolates varies depending this website on the geographic regions, with Candida albicans (C. albicans) being

the most commonly isolated species in Candidaemia according to a 10.5-year global survey (Pfaller et al., 2010), from the lowest frequency (48.9%) in North America to the highest one (67.9%) in European; however, there is an upward trend in the frequency of isolation of non-albicans species (NAC), likely due to reduced susceptibility to antifungal agents in some NAC (Lai et al., 2008; Pfaller & Diekema, 2010; Pfaller, 2012). In the management of fungal infections, there have been significant recent advances in antifungal therapy, including the introduction of a new generation of antifungal agents, the use of combination therapy, and improved standardization of susceptibility testing; however, drug resistance still poses a challenge in the management and treatment of fungal infections (Kanafani & Perfect, 2008; Chapeland-Leclerc et al., 2010; Pfaller, 2012). In the United States, the treatment associated with Candidemia cost more than US $1 billion annually (Beck-Sague & Jarvis, 1993; Miller et al., 2001). The high mortality rate, the rapid Carbachol development of drug resistance, and the high cost associated with therapeutic treatment make Candida spp. a medically important group of fungal pathogens. Antimicrobial resistance has become increasingly

important in antifungal therapy. Resistance to nearly all major antifungal agents has been reported in clinical isolates of Candida spp. (Marr et al., 1998; Sanglard & Odds, 2002; Katiyar et al., 2006), which poses a major public health concern as the arsenal of antifungal agents is limited. Single nucleotide polymorphism, loss-of-heterozygosity (LOH) and gross chromosomal rearrangements have been found to be important processes in the development of drug resistance (Selmecki et al., 2006, 2008, 2009). Research within the past couple of decades has identified numerous drug resistance mechanisms. Mutations in drug targets, such as ERG11 in fluconazole resistance and FKS1 in echinocandin resistance (Loffler et al., 1997; Lamb et al., 2000; White et al., 2002; Park et al.