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Microbes are constantly confronted with changes and challenges in their environment. A proper response to these environmental cues is needed for optimal cellular functioning and fitness. Interestingly, past exposure to environmental cues can accelerate or boost the response when this condition returns, even in daughter cells that have not directly encountered the initial cue. Moreover, this behavior is mostly epigenetic and often goes hand in hand with strong heterogeneity in the strength and speed of the response between isogenic cells of the same population, which might function as a bet-hedging strategy. In this review, we discuss examples of history-dependent behavior (HDB) or "memory," with a specific focus on HDB in fluctuating environments. In most examples discussed, the lag time before the response to an environmental change is used as an experimentally measurable proxy for HDB. We highlight different mechanisms already implicated in HDB, and by using HDB in fluctuating carbon conditions as a case study, we showcase how the metabolic state of a cell can be a key determining factor for HDB. Finally, we consider possible evolutionary causes and consequences of such HDB. [ABSTRACT FROM AUTHOR]

Histone acetylation, which is critical for transcriptional regulation and various biological processes in eukaryotes, is a reversible dynamic process regulated by HATs and HDACs. This study determined the function of 6 histone acetyltransferases (HATs) (Gcn5 , RTT109 , Elp3 , Sas3 , Sas2 , Nat3) and 6 histone deacetylases (HDACs) (Hos2 , Rpd3 , Hda1 , Hos3 , Hst2 , Sir2) in the phytopathogenic fungus Alternaria alternata by analyzing targeted gene deletion mutants. Our data provide evidence that HATs and HDACs are both required for mycelium growth, cell development and pathogenicity as many gene deletion mutants (Δ Gcn5 , Δ RTT109 , Δ Elp3 , Δ Sas3 , Δ Nat3 , Δ Hos2 , and Δ Rpd3) displayed reduced growth, conidiation or virulence at varying degrees. In addition, HATs and HDACs are involved in the resistance to multiple stresses such as oxidative stress (Sas3 , Gcn5 , Elp3 , RTT109 , Hos2), osmotic stress (Sas3 , Gcn5 , RTT109 , Hos2), cell wall-targeting agents (Sas3 , Gcn5 , Hos2), and fungicide (Gcn5 , Hos2). Δ Gcn5 , Δ Sas3 , and Δ Hos2 displayed severe growth defects on sole carbon source medium suggesting a vital role of HATs and HDACs in carbon source utilization. More SNPs were generated in Δ Gcn5 in comparison to wild-type when they were exposed to ultraviolet ray. Moreover, Δ RTT109 , Δ Gcn5 , and Δ Hos2 showed severe defects in resistance to DNA-damaging agents, indicating the critical role of HATs and HDACs in DNA damage repair. These phenotypes correlated well with the differentially expressed genes in Δ Gcn5 and Δ Hos2 that are essential for carbon sources metabolism, DNA damage repair, ROS detoxification, and asexual development. Furthermore, Gcn5 is required for the acetylation of H3K4. Overall, our study provides genetic evidence to define the central role of HATs and HDACs in the pathological and biological functions of A. alternata. [ABSTRACT FROM AUTHOR]

Cells face major changes in demand for and supply of inorganic phosphate (Pi). Pi is often a limiting nutrient in the environment, particularly for plants and microorganisms. At the same time, the need for phosphate varies, establishing conflicts of goals. Cells experience strong peaks of Pi demand, e.g., during the S-phase, when DNA, a highly abundant and phosphate-rich compound, is duplicated. While cells must satisfy these Pi demands, they must safeguard themselves against an excess of Pi in the cytosol. This is necessary because Pi is a product of all nucleotide-hydrolyzing reactions. An accumulation of Pi shifts the equilibria of these reactions and reduces the free energy that they can provide to drive endergonic metabolic reactions. Thus, while Pi starvation may simply retard growth and division, an elevated cytosolic Pi concentration is potentially dangerous for cells because it might stall metabolism. Accordingly, the consequences of perturbed cellular Pi homeostasis are severe. In eukaryotes, they range from lethality in microorganisms such as yeast (Sethuraman et al., 2001; Hürlimann, 2009), severe growth retardation and dwarfism in plants (Puga et al., 2014; Liu et al., 2015; Wild et al., 2016) to neurodegeneration or renal Fanconi syndrome in humans (Legati et al., 2015; Ansermet et al., 2017). Intracellular Pi homeostasis is thus not only a fundamental topic of cell biology but also of growing interest for medicine and agriculture. [ABSTRACT FROM AUTHOR]

Ubiquitin is a small modifier protein which is usually conjugated to substrate proteins for degradation. In recent years, a number of ubiquitin-like proteins have been identified; however, their roles in eukaryotes are largely unknown. Here, we describe a ubiquitin-like protein URM1, and found it plays important roles in the development and infection process of the rice blast fungus, Magnaporthe oryzae. Targeted deletion of URM1 in M. oryzae resulted in slight reduction in vegetative growth and significant decrease in conidiation. More importantly, the Δ urm1 mutant also showed evident reduction in virulence to host plants. Infection process observation demonstrated that the mutant was arrested in invasive growth and resulted in accumulation of massive host reactive oxygen species (ROS). Further, we found the Δ urm1 mutant was sensitive to the cell wall disturbing reagents, thiol oxidizing agent diamide and rapamycin. We also showed that URM1-mediated modification was responsive to oxidative stresses, and the thioredoxin peroxidase Ahp1 was one of the important urmylation targets. These results suggested that URM1-mediated urmylation plays important roles in detoxification of host oxidative stress to facilitate invasive growth in M. oryzae. [ABSTRACT FROM AUTHOR]

Pyrococcus furiosus DSM 3638 is a model organism for hyperthermophilic archaea with an optimal growth temperature near 100°C. The genome was sequenced about 18 years ago. However, some publications suggest that in contrast to other Pyrococcus species, the genome of P. furiosus DSM 3638 is prone to genomic rearrangements. Therefore, we re-sequenced the genome using third generation sequencing techniques. The new de novo assembled genome is 1,889,914 bp in size and exhibits high sequence identity to the published sequence. However, two major deviations were detected: (1) The genome is 18,342 bp smaller than the NCBI reference genome due to a recently described deletion. (2) The region between PF0349 and PF0388 is inverted most likely due an assembly problem for the original sequence. In addition, numerous minor variations, ranging from single nucleotide exchanges, deletions or insertions were identified. The total number of insertion sequence (IS) elements is also reduced from 30 to 24 in the new sequence. Re-sequencing of a 2-year-old "lab culture" using Nanopore sequencing confirmed the overall stability of the P. furiosus DSM 3638 genome even under normal lab conditions without taking any special care. To improve genome annotation, the updated DNA sequence was combined with an RNA sequencing approach. Here, RNAs from eight different growth conditions were pooled to increase the number of detected transcripts. Furthermore, a differential RNA-Seq approach was employed for the identification of transcription start sites (TSSs). In total, 2515 TSSs were detected and classified into 834 primary (pTSS), 797 antisense (aTSS), 739 internal and 145 secondary TSSs. Our analysis of the upstream regions revealed a well conserved archaeal promoter structure. Interrogation of the distances between pTSSs and aTSSs revealed a significant number of antisense transcripts, which are a result of bidirectional transcription from the same TATA box. This mechanism of antisense transcript production could be further confirmed by in vitro transcription experiments. We assume that bidirectional transcription gives rise to non-functional antisense RNAs and that this is a widespread phenomenon in archaea due to the architecture of the TATA element and the symmetric structure of the TATA-binding protein. [ABSTRACT FROM AUTHOR]

Aspergillus flavus is an opportunistic pathogenic fungus for both plant and animal that produces carcinogenic toxins termed aflatoxins (AFs). To identify possible genetic targets to reduce AF contamination, in this study, we have characterized a novel A. flavus Set3, and it shares sequence homology with the yeast protein Set3. The set3 deletion mutants present no difference in growth rate but alterations in asexual development and secondary metabolite production when compared to the A. flavus wild type. Specifically, deletion of set3 gene decreases conidiophore formation and conidial production through downregulating expression of brlA and abaA genes. In addition, normal levels of set3 are required for sclerotial development and expression of sclerotia-related genes nsdC and sclR. Further analyses demonstrated that Set3 negatively regulates AF production as well as the concomitant expression of genes in the AF gene cluster. Importantly, our results also display that A. flavus Set3 is involved in crop kernel colonization. Taking together, these results reveal that a novel Set3 plays crucial roles in morphological development, secondary metabolism, and fungal virulence in A. flavus. [ABSTRACT FROM AUTHOR]

Temperatures had a strong effect on many life history traits, including growth, development and reproduction. At near-freezing temperatures (0–4°C), yeast cells could trigger series of biochemical reactions to respond and adapt to the stress, protect them against sever cold and freeze injury. Different Saccharomyces cerevisiae strains vary greatly in their ability to grow at near-freezing temperatures. However, the molecular mechanisms that allow yeast cells to sustain this response are not yet fully understood and the genetic basis of tolerance and sensitivity to near-freeze stress remains unclear. Uncovering the genetic determinants of this trait is, therefore, of is of significant interest. In order to investigate the genetic basis that underlies near-freezing temperature tolerance in S. cerevisiae , we mapped the major quantitative trait loci (QTLs) using bulk segregant analysis (BSA) in the F2 segregant population of two Chinese indigenous S. cerevisiae strains with divergent tolerance capability at 4°C. By genome-wide comparison of single-nucleotide polymorphism (SNP) profiles between two bulks of segregants with high and low tolerance to near-freezing temperature, a hot region located on chromosome IV was identified tightly associated with the near-freezing temperature tolerance. The Reciprocal hemizygosity analysis (RHA) and gene deletion was used to validate the genes involved in the trait, showed that the gene NAT1 plays a role in the near-freezing temperature tolerance. This study improved our understanding of the genetic basis of the variability of near-freezing temperature tolerance in yeasts. The superior allele identified could be used to genetically improve the near-freezing stress adaptation of industrial yeast strains. [ABSTRACT FROM AUTHOR]

Fungi are generally benign members of the human mucosal flora or live as saprophytes in the environment. However, they can become pathogenic, leading to invasive and life threatening infections in vulnerable patients. These invasive fungal infections are regarded as a major public health problem on a similar scale to tuberculosis or malaria. Current treatment for these infections is based on only four available drug classes. This limited therapeutic arsenal and the emergence of drug-resistant strains are a matter of concern due to the growing number of patients to be treated, and new therapeutic strategies are urgently needed. Adaptation of fungi to drug pressure involves transcriptional regulation, in which chromatin dynamics and histone modifications play a major role. Histone deacetylases (HDACs) remove acetyl groups from histones and actively participate in controlling stress responses. HDAC inhibition has been shown to limit fungal development, virulence, biofilm formation, and dissemination in the infected host, while also improving the efficacy of existing antifungal drugs toward Candida spp. In this article, we review the functional roles of HDACs and the biological effects of HDAC inhibitors on Candida spp., highlighting the correlations between their pathogenic effects in vitro and in vivo. We focus on how HDAC inhibitors could be used to treat invasive candidiasis while also reviewing recent developments in their clinical evaluation. [ABSTRACT FROM AUTHOR]