The Clock Keeps on Ticking: Emerging Roles for Circadian Regulation in the Control of Fungal Physiology and Pathogenesis.

Tic-tac, tic-tac, the sound of time is familiar to us, yet, it also silently shapes daily biological processes conferring 24-hour rhythms in, among others, cellular and systemic signaling, gene expression, and metabolism. Indeed, circadian clocks are molecular machines that permit temporal control of a variety of processes in individuals, with a close to 24-hour period, optimizing cellular dynamics in synchrony with daily environmental cycles. For over three decades, the molecular bases of these clocks have been extensively described in the filamentous fungus Neurospora crassa, yet, there have been few molecular studies in fungi other than Neurospora, despite evidence of rhythmic phenomena in many fungal species, including pathogenic ones. This chapter will revise the mechanisms underlying clock regulation in the model fungus N. crassa, as well as recent findings obtained in several fungi. In particular, this chapter will review the effect of circadian regulation of virulence and organismal interactions, focusing on the phytopathogen Botrytis cinerea, as well as several entomopathogenic fungi, including the behavior-manipulating species Ophiocordyceps kimflemingiae and Entomophthora muscae. Finally, this review will comment current efforts in the study of mammalian pathogenic fungi, while highlighting recent circadian lessons from parasites such as Trypanosoma and Plasmodium. The clock keeps on ticking, whether we can hear it or not.