Antimicrobial resistance in the wild: Insights from epigenetics.

Spreading of bacterial and fungal strains that are resistant to antimicrobials poses a serious threat to the well-being of humans, animals, and plants. Antimicrobial resistance has been mainly investigated in clinical settings. However, throughout their evolutionary history microorganisms in the wild have encountered antimicrobial substances, forcing them to evolve strategies to combat antimicrobial action. It is well known that many of these strategies are based on genetic mechanisms, but these do not fully explain important aspects of the antimicrobial response such as the rapid development of resistance, reversible phenotypes, and hetero-resistance. Consequently, attention has turned toward epigenetic pathways that may offer additional insights into antimicrobial mechanisms. The aim of this review is to explore the epigenetic mechanisms that confer antimicrobial resistance, focusing on those that might be relevant for resistance in the wild. First, we examine the presence of antimicrobials in natural settings. Then we describe the documented epigenetic mechanisms in bacteria and fungi associated with antimicrobial resistance and discuss innovative epigenetic editing techniques to establish causality in this context. Finally, we discuss the relevance of these epigenetic mechanisms on the evolutionary dynamics of antimicrobial resistance in the wild, emphasizing the critical role of priming in the adaptation process. We underscore the necessity of incorporating non-genetic mechanisms into our understanding of antimicrobial resistance evolution. These mechanisms offer invaluable insights into the dynamics of antimicrobial adaptation within natural ecosystems.

Parental effects in a filamentous fungus: Phenotype, fitness and mechanism.

In nature, organisms have to cope with constantly changing environments. In certain conditions, it may be advantageous for the parents to pass on information about the environment, or resources to their offspring. Such transfers are known as parental effects, and they are well documented in plants and animals, but not in other eukaryotes, such as fungi. Many fungi disperse through spores, and fungal spores can potentially carry information or resources to the next generation. Understanding parental effects and their evolutionary consequences in fungi is of vital importance as they perform crucial ecosystem functions. In this study, we investigated whether parental effects are present in the filamentous fungus Neurospora crassa, how long do they last, whether the effects are adaptive, and what is their mechanism. We performed a fully factorial match/mismatch experiment for a good and a poor quality environment, in which we measured the initial growth of strains that experienced either a matched or mismatched environment in their previous generation. We found a strong silver-spoon effect in initial mycelium growth, which lasted for one generation, and increased fitness during competition experiments. By using deletion mutants that lacked key genes in epigenetic processes, we show that epigenetic mechanisms are not involved in this effect. Instead, we show that spore glycogen content, glucose availability and a radical transcription shift in spores are the main mechanisms behind this parental effect.

Chromatin structure influences rate and spectrum of spontaneous mutations in Neurospora crassa.

Although mutation rates have been extensively studied, variation in mutation rates throughout the genome is poorly understood. To understand patterns of genetic variation, it is important to understand how mutation rates vary. Chromatin modifications may be an important factor in determining variation in mutation rates in eukaryotic genomes. To study variation in mutation rates, we performed a mutation accumulation (MA) experiment in the filamentous fungus Neurospora crassa and sequenced the genomes of the 40 MA lines that had been propagated asexually for approximately 1015 [Formula: see text] mitoses. We detected 1322 mutations in total and observed that the mutation rate was higher in regions of low GC, in domains of H3K9 trimethylation, in centromeric regions, and in domains of H3K27 trimethylation. The rate of single-nucleotide mutations in euchromatin was [Formula: see text] In contrast, the mutation rate in H3K9me3 domains was 10-fold higher: 2.43 [Formula: see text] We also observed that the spectrum of single-nucleotide mutations was different between H3K9me3 and euchromatic domains. Our statistical model of mutation rate variation predicted a moderate amount of extant genetic variation, suggesting that the mutation rate is an important factor in determining levels of natural genetic variation. Furthermore, we characterized mutation rates of structural variants, complex mutations, and the effect of local sequence context on the mutation rate. Our study highlights that chromatin modifications are associated with mutation rates, and accurate evolutionary inferences should take variation in mutation rates across the genome into account.

DNA methylation patterns respond to thermal stress in the viviparous cockroach Diploptera punctata.

It is increasingly recognized that epigenetic mechanisms play a key role in acclimatization and adaptation to thermal stress in invertebrates. DNA methylation and its response to temperature variation has been poorly studied in insects. Here, we investigated DNA methylation and hydroxymethylation patterns in the viviparous cockroach Diploptera punctata at a global and gene specific level in response to variation in temperature. We specifically studied methylation percentage in the heat shock protein 70 (Hsp70), whose function is linked to thermal plasticity and resistance. We found high levels of DNA methylation in several tissues but only low levels of DNA hydroxymethylation in the brain. Hsp70 methylation patterns showed significant differences in response to temperature. We further found that global DNA methylation variation was considerably lower at 28°C compared to higher or lower temperatures, which may be indicative of the optimal temperature for this species. Our results demonstrate that DNA methylation could provide a mechanism for insects to dynamically respond to changing temperature conditions in their environment.