Date Published: February 2, 2017
Publisher: Public Library of Science
Author(s): Paul Dahlin, Vaibhav Srivastava, Sophia Ekengren, Lauren S. McKee, Vincent Bulone, Mark Gijzen.
The oomycete class includes pathogens of animals and plants which are responsible for some of the most significant global losses in agriculture and aquaculture. There is a need to replace traditional chemical means of controlling oomycete growth with more targeted approaches, and the inhibition of sterol synthesis is one promising area. To better direct these efforts, we have studied sterol acquisition in two model organisms: the sterol-autotrophic Saprolegnia parasitica, and the sterol-heterotrophic Phytophthora infestans. We first present a comprehensive reconstruction of a likely sterol synthesis pathway for S. parasitica, causative agent of the disease saprolegniasis in fish. This pathway shows multiple potential routes of sterol synthesis, and draws on several avenues of new evidence: bioinformatic mining for genes with sterol-related functions, expression analysis of these genes, and analysis of the sterol profiles in mycelium grown in different media. Additionally, we explore the extent to which P. infestans, which causes the late blight in potato, can modify exogenously provided sterols. We consider whether the two very different approaches to sterol acquisition taken by these pathogens represent any specific survival advantages or potential drug targets.
The sterols are a highly diverse group of isoprenoid-derived amphipathic biomolecules which play important structural and physical roles in all eukaryotic cells [1–6]. The precursors to sterol synthesis are isopentenyl diphosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), which arise via the mevalonate (MVA) pathway, or alternatively via the methylerythritol phosphate (MEP) pathway in green algae and some red algae [7, 8].
Since sterols are vital for oomycete survival, we emphasise the importance of these molecules as potential drug targets in control strategies. However, the acquisition of these lipids differs greatly between the Saprolegniales and Peronosporales, which will limit the range of applicability of any sterol-targeting treatments. We have shown that the fish pathogen S. parasitica can produce a range of different sterols. The sterol profile in the mycelium is altered by changing the growth medium, which correlates with alterations in the level of expression of sterol synthesising genes. Our data indicate that the profile of sterols synthesised in a natural setting is likely to be host-dependent, and that S. parasitica could compensate for the loss of one sterol synthesis route. This observation should inform the design of control strategies. Nonetheless, the complex sterol synthesis pathway we present for S. parasitica may lead to the identification of some specific targets for inhibition. We have additionally confirmed that in our experimental set-up P. infestans mycelial growth is absolutely dependent upon sterol uptake, and found no evidence that the organism can modify exogenous sterols despite possessing some genes for sterol modification. We expect that future investigations into the inhibition of sterol uptake by P. infestans might be more successful by focussing on the elicitin proteins, which are likely key to sterol uptake by this devastating pathogen.