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Volume 5, Issue 2, pp. 63 - 118, February 2018

Issue cover
Cover: The colored micrograph features the grouping of numerous gram negative, anaerobic Borrelia burgdorferi bacteria (image by Jamice Haney Carr and Claudia Molins, US Centers for Disease Control and Prevention, USA); image modified by MIC. The cover is published under the Creative Commons Attribution (CC BY) license. Enlarge issue cover

Reviews

Ras signalling in pathogenic yeasts

Daniel R. Pentland, Elliot Piper-Brown, Fritz A. Mühlschlegel and Campbell W. Gourlay

page 63-73 | 10.15698/mic2018.02.612 | Full text | PDF | Abstract

The small GTPase Ras acts as a master regulator of growth, stress response and cell death in eukaryotic cells. The control of Ras activity is fundamental, as highlighted by the oncogenic properties of constitutive forms of Ras proteins. Ras also plays a crucial role in the pathogenicity of fungal pathogens where it has been found to regulate a number of adaptions required for virulence. The importance of Ras in fungal disease raises the possibility that it may provide a useful target for the development of new treatments at a time when resistance to available antifungals is increasing. New findings suggest that important regulatory sequences found within fungal Ras proteins that are not conserved may prove useful in the development of new antifungals. Here we review the roles of Ras protein function and signalling in the major human yeast pathogens Candida albicans and Cryptococcus neoformans and discuss the potential for targeting Ras as a novel approach to anti-fungal therapy.

Research Articles

Untargeted metabolomics confirms and extends the understanding of the impact of aminoimidazole carboxamide ribotide (AICAR) in the metabolic network of Salmonella enterica

Jannell V. Bazurto, Stephen P. Dearth, Eric D. Tague, Shawn R. Campagna and Diana M. Downs

page 74-87 | 10.15698/mic2018.02.613 | Full text | PDF | Abstract

In Salmonella enterica, aminoimidazole carboxamide ribotide (AICAR) is a purine biosynthetic intermediate and a substrate of the AICAR transformylase/IMP cyclohydrolase (PurH) enzyme. When purH is eliminated in an otherwise wild-type strain, AICAR accumulates and indirectly inhibits synthesis of the essential coenzyme thiamine pyrophosphate (TPP). In this study, untargeted metabolomics approaches were used to i) corroborate previously defined metabolite changes, ii) define the global consequences of AICAR accumulation and iii) investigate the metabolic effects of mutations that restore thiamine prototrophy to a purH mutant. The data showed that AICAR accumulation led to an increase in the global regulator cyclic AMP (cAMP) and that disrupting central carbon metabolism could decrease AICAR and/or cAMP to restore thiamine synthesis. A mutant (icc) blocked in cAMP degradation that accumulated cAMP but had wild-type levels of AICAR was used to identify changes in the purH metabolome that were a direct result of elevated cAMP. Data herein describe the use of metabolomics to identify the metabolic state of mutant strains and probe the underlying mechanisms used by AICAR to inhibit thiamine synthesis. The results obtained provide a cautionary tale of using metabolite concentrations as the only data to define the physiological state of a bacterial cell.

Fat storage-inducing transmembrane (FIT or FITM) proteins are related to lipid phosphatase/phosphotransferase enzymes

Matthew J Hayes, Vineet Choudhary, Namrata Ojha, John JH Shin, Gil-Soo Han, George M. Carman, Christopher JR Loewen, William A Prinz and Timothy P Levine

page 88-103 | 10.15698/mic2018.02.614 | Full text | PDF | Abstract

Fat storage-inducing transmembrane (FIT or FITM) proteins have been implicated in the partitioning of triacylglycerol to lipid droplets and the budding of lipid droplets from the ER. At the molecular level, the sole relevant interaction is that FITMs directly bind to triacyglycerol and diacylglycerol, but how they function at the molecular level is not known. Saccharomyces cerevisiae has two FITM homologues: Scs3p and Yft2p. Scs3p was initially identified because deletion leads to inositol auxotrophy, with an unusual sensitivity to addition of choline. This strongly suggests a role for Scs3p in phospholipid biosynthesis. Looking at the FITM family as widely as possible, we found that FITMs are widespread throughout eukaryotes, indicating presence in the last eukaryotic common ancestor. Protein alignments also showed that FITM sequences contain the active site of lipid phosphatase/phosphotransferase (LPT) enzymes. This large family transfers phosphate-containing headgroups either between lipids or in exchange for water. We confirmed the prediction that FITMs are related to LPTs by showing that single amino-acid substitutions in the presumptive catalytic site prevented their ability to rescue growth of the mutants on low inositol/high choline media when over-expressed. The substitutions also prevented rescue of other phenotypes associated with loss of FITM in yeast, including mistargeting of Opi1p, defective ER morphology, and aberrant lipid droplet budding. These results suggest that Scs3p, Yft2p and FITMs in general are LPT enzymes involved in an as yet unknown critical step in phospholipid metabolism.

Research Reports

Yeast quiescence exit swiftness is influenced by cell volume and chronological age

Damien Laporte, Laure Jimenez, Laëtitia Gouleme, Isabelle Sagot

page 104-111 | 10.15698/mic2018.02.615 | Full text | PDF | Abstract

Quiescence exit swiftness is crucial not only for micro-organisms in competition for an environmental niche, such as yeast, but also for the maintenance of tissue homeostasis in multicellular species. Here we explore the effect of replicative and chronological age on Saccharomyces cerevisiae quiescence exit efficiency. Our study reveals that this step strongly relies on the cell volume in quiescence but is not influenced by cell replicative age, at least for cells that have undergone less than 10 divisions. Furthermore, we establish that chronological age strongly impinges on cell’s capacities to exit quiescence. This effect is not related to cell volume or due to cell’s inability to metabolize external glucose but rather seems to depend on intracellular trehalose concentration. Overall, our data illustrate that the quiescent state is a continuum evolving with time, early and deep quiescence being distinguishable by the cell’s proficiency to re-enter the proliferation cycle.

Meeting Reports

New perspectives from South-Y-East, not all about death

A report of the 12th lnternational Meeting on Yeast Apoptosis in Bari, Italy, May 14th-18th, 2017

Nicoletta Guaragnella, Mariarita Stirpe, William Burhans, Manuela Côrte-Real, Campbell Gourlay, Paula Ludovico, Frank Madeo, Dina Petranovic, Joris Winderickx, Cristina Mazzoni and Sergio Giannattasio

page 112-115 | 10.15698/mic2018.02.616 | Full text | PDF |

Microreviews

Burkholderia gladioli strain NGJ1 deploys a prophage tail-like protein for mycophagy

Rahul Kumar, Sunil Kumar Yadav, Durga Madhab Swain and Gopaljee Jha

page 116-118 | 10.15698/mic2018.02.617 | Full text | PDF | Abstract

Fungal pathogens are responsible for approximately two third of the infectious plant diseases. Historically they have been associated with several devastating famines, causing death and disabilities in humans. Mostly fungal diseases are being controlled by using fungicides which otherwise have adverse side effects on the health of consumers as well as environment. Due to extensive usages, pathogens have evolved resistance against most of the commonly used fungicides and rendered them ineffective. Controlling fungal disease in a sustainable and eco-friendly fashion remains a challenge. The antifungal biocontrol agents are being considered as potent, alternative and ecofriendly approach to manage fungal diseases. In our recent work, we have identified a rice associated bacterium; Burkholderia gladioli strain NGJ1 which demonstrates broad spectrum fungal eating (mycophagous) property. We determined that the bacterium utilizes its type III secretion system (Injectisome) machinery to deploy a prophage tail-like protein (Bg_9562) into fungal cells to devour them. The purified Bg_9562 protein from over-expressing recombinant E. coli strain demonstrates broad spectrum antifungal activity. Overall our study opens up a new opportunity to exploit prophage tail-like protein as potent antifungal compound to control plant as well as animal fungal diseases.