On the emergence, spread and resistance of : host, pathogen and environmental tipping points.

Over a decade ago, a multidrug-resistant nosocomial fungus emerged worldwide and has since become a significant challenge for clinicians and microbiologists across the globe. A resilient pathogen, survives harsh disinfectants, desiccation and high-saline environments. It readily colonizes the inanimate environment, susceptible patients and causes invasive infections that exact a high toll. Prone to misidentification by conventional microbiology techniques, rapidly acquires multiple genetic determinants that confer multidrug resistance. Whole-genome sequencing has identified four distinct clades of , and possibly a fifth one, in circulation. Even as our understanding of this formidable pathogen grows, the nearly simultaneous emergence of its distinct clades in different parts of the world, followed by their rapid global spread, remains largely unexplained. We contend that certain host-pathogen-environmental factors have been evolving along adverse trajectories for the last few decades, especially in regions where originally appeared, until these factors possibly reached a tipping point to compel the evolution, emergence and spread of . Comparative genomics has helped identify several resistance mechanisms in that are analogous to those seen in other species, but they fail to fully explain how high-level resistance rapidly develops in this yeast. A better understanding of these unresolved aspects is essential not only for the effective management of patients, hospital outbreaks and its global spread but also for forecasting and tackling novel resistant pathogens that might emerge in the future. In this review, we discuss the emergence, spread and resistance of , and propose future investigations to tackle this resilient pathogen.