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Volume 5, Issue 11, pp. 472 - 524, November 2018

Issue cover
Cover: Microscopic image of encapsulated Cryptococcus neoformans cells. The polysaccharide capsule is the most important virulence factor in this fungal pathogen. Cells were stained with India ink to visualize the capsule as a light halo around the fungal cell body. The image was acquired using Differential Interference Contrast Microscopy (image by François L. Mayer; University of British Columbia, Canada); image modified by MIC. The cover is published under the Creative Commons Attribution (CC BY) license. Enlarge issue cover

Reviews

Protective roles of ginseng against bacterial infection

Ye-Ram Kim and Chul-Su Yang

page 472-481 | 10.15698/mic2018.11.654 | Full text | PDF | Abstract

Ginseng (Panax ginseng Meyer) is a well-known traditional herbal medicine that plays a protective role against microbial attack. Several studies have revealed its anti-cancer, anti-inflammatory, and immune-modulatory effects. Ginseng contains several components that vary according to the year of cultivation and the processing method used, such as heating, drying, and steaming, which induce different degrees of pharmacological activities. This review discusses the antibacterial effects of ginseng against pathogenic bacterial infections. We describe how ginseng regulates pathogenic factors that are harmful to the host and discuss the therapeutic potential of ginseng as a natural antibacterial drug to combat bacterial infectious disease, which is a global public health challenge. The components of ginseng could be novel alternatives to solve the growing problem of antibiotic resistance and toxicity.

Conventional and emerging roles of the energy sensor Snf1/AMPK in Saccharomyces cerevisiae

Paola Coccetti, Raffaele Nicastro and Farida Tripodi

page 482-494 | 10.15698/mic2018.11.655 | Full text | PDF | Abstract

All proliferating cells need to match metabolism, growth and cell cycle progression with nutrient availability to guarantee cell viability in spite of a changing environment. In yeast, a signaling pathway centered on the effector kinase Snf1 is required to adapt to nutrient limitation and to utilize alternative carbon sources, such as sucrose and ethanol. Snf1 shares evolutionary conserved functions with the AMP-activated Kinase (AMPK) in higher eukaryotes which, activated by energy depletion, stimulates catabolic processes and, at the same time, inhibits anabolism. Although the yeast Snf1 is best known for its role in responding to a number of stress factors, in addition to glucose limitation, new unconventional roles of Snf1 have recently emerged, even in glucose repressing and unstressed conditions. Here, we review and integrate available data on conventional and non-conventional functions of Snf1 to better understand the complexity of cellular physiology which controls energy homeostasis.

Research Articles

A chemical genetic screen reveals a role for proteostasis in capsule and biofilm formation by Cryptococcus neoformans

François L. Mayer, Eddy Sánchez-León, James W. Kronstad

page 495-510 | 10.15698/mic2018.11.656 | Full text | PDF | Abstract

Pathogenic microorganisms employ specialized virulence factors to cause disease. Biofilm formation and the production of a polysaccharide capsule are two important virulence factors in Cryptococcus neoformans, the fungal pathogen that causes meningoencephalitis. Here, we show that the bipolar disorder drug lithium inhibits formation of both virulence factors by a mechanism involving dysregulation of the ubiquitin/proteasome system. By using a chemical genetics approach and bioinformatic analyses, we describe the cellular landscape affected by lithium treatment. We demonstrate that lithium affects many different pathways in C. neoformans, including the cAMP/protein kinase A, inositol biosynthesis, and ubiquitin/proteasome pathways. By analyzing mutants with defects in the ubiquitin/proteasome system, we uncover a role for proteostasis in both capsule and biofilm formation. Moreover, we demonstrate an additive influence of lithium and the proteasome inhibitor bortezomib in inhibiting capsule production, thus establishing a link between lithium activity and the proteasome system. Finally, we show that the lithium-mimetic drug ebselen potently blocks capsule and biofilm formation, and has additive activity with lithium or bortezomib. In summary, our results illuminate the impact of lithium on C. neoformans, and link dysregulation of the proteasome to capsule and biofilm inhibition in this important fungal pathogen.

Nutritional and meiotic induction of transiently heritable stress resistant states in budding yeast

Heldder Gutierrez, Bakhtiyar Taghizada, and Marc D. Meneghini

page 511-521 | 10.15698/mic2018.11.657 | Full text | PDF | Abstract

Transient exposures to environmental stresses induce altered physiological states in exposed cells that persist after the stresses have been removed. These states, referred to as cellular memory, can even be passed on to daughter cells and may thus be thought of as embodying a form of epigenetic inheritance. We find that meiotically produced spores in the budding yeast S. cerevisiae possess a state of heightened stress resistance that, following their germination, persists for numerous mitotic generations. As yeast meiotic development is essentially a starvation response that a/alpha diploid cells engage, we sought to model this phenomenon by subjecting haploid cells to starvation conditions. We find also that haploid cells exposed to glucose withdrawal acquire a state of elevated stress resistance that persists after the reintroduction of these cells to glucose-replete media. Following release from lengthy durations of glucose starvation, we confirm that this physiological state of enhanced stress resistance is propagated in descendants of the exposed cells through two mitotic divisions before fading from the population. In both haploid starved cells and diploid produced meiotic spores we show that their cellular memories are not attributable to trehalose, a widely regarded stress protectant that accumulates in these cell types. Moreover, the transiently heritable stress resistant state induced by glucose starvation in haploid cells is independent of the Msn2/4 transcription factors, which are known to program cellular memory induced by exposure of cells to NaCl. Our findings identify new developmentally and nutritionally induced states of cellular memory that exhibit striking degrees of persistence and mitotic heritability.

Microreviews

A comparative approach to decipher intestinal animal-microbe associations

Keisuke Nakashima

page 522-524 | 10.15698/mic2018.11.658 | Full text | PDF | Abstract

Mammalian guts harbor indigenous microbes that are integral to host health. Microbiome research using sophisticated model organisms has provided insights into intricate interactions between microbiota and host animals. However, it remains unclear how these animal-microbe associations developed. We have recently addressed this question via comparative analyses of chordates, given that complex biological systems can be resolved into ancestral and derived elements when examined in an evolutionary framework (Nat Commun 9: 3402). Results support the view that microbial colonization of the mucus layer that overlies mammalian gastrointestinal epithelium was established upon loss of ancestral chitin-based barrier immunity. Comparative approaches enable us to arrange ongoing biological processes into host natural history for better understanding of intestinal animal-microbe associations.

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