Heteroresistance: a hidden cause behind antifungal prophylaxis failure
Invasive fungal infections in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients on antimicrobial prophylaxis is a major cause of infectious mortality, although its underlying pathophysiological mechanisms remain unclear. In a new report, Zhai and colleagues provide evidence that heteroresistance drives breakthrough Candida parapsilosis bloodstream infections in allo-HSCT recipients receiving micafungin prophylaxis.
TldR: TnpB's evolutionary shift from transposon nucleases to RNA-guided transcriptional regulators
TnpB proteins are transposon-encoded nucleases involved in transposon DNA propagation. Wiegand et al. identified a new class of TnpB-derived proteins, called TnpB-like nuclease-dead repressors (TldRs), which function as RNA-guided transcriptional regulators targeting conserved promoter regions. In Enterobacteriaceae, bacteriophages use TldRs and an adjacent phage gene to modulate host flagellar assembly.
Tradeoffs and constraints on the evolution of tailocins
Phage tail-like bacteriocins (tailocins) are protein complexes produced by bacteria with the potential to kill their neighbors. Widespread throughout Gram-negative bacteria, tailocins exhibit extreme specificity in their targets, largely killing closely related strains. Despite their presence in diverse bacteria, the impact of these competitive weapons on the surrounding microbiota is largely unknown. Recent studies revealed the rapid evolution and genetic diversity of tailocins in microbial communities and suggest that there are constraints on the evolution of specificity and resistance. Given the precision of their targeted killing and the ease of engineering new specificities, understanding the evolution and ecological impact of tailocins may enable the design of promising candidates for novel targeted antibiotics.
From advisors to mentors: fostering supportive mentorship in academia
A supportive mentorship has long-lasting effects on shaping students' personal and professional development. Here, we outline important aspects of mentoring and indicators of good mentors, focusing on effective mutualistic interaction. We believe that traditional academic advice should be expanded to include supportive group mentoring to foster future top scientific talent.
Short-chain fatty acids in viral infection: the underlying mechanisms, opportunities, and challenges
Viral infections can cause cellular pathway derangements, cell death, and immunopathological responses, leading to host inflammation. Short-chain fatty acids (SCFAs), produced by the microbiota, have emerged as a potential therapeutic for viral infections due to their ability to modulate these processes. However, SCFAs have been reported to have both beneficial and detrimental effects, necessitating a comprehensive understanding of the underlying mechanisms. This review highlights the complex mechanisms underlying SCFAs' effects on viral infection outcomes. We also emphasize the importance of considering how SCFAs' activities may differ under diverse contexts, including but not limited to target cells with different metabolic wiring, different viral causes of infection, the target organism/cell's nutrient availability and/or energy balance, and hosts with varying microbiome compositions.
Tea plant microorganisms in the improvement of tea quality
Microorganisms residing in different parts of tea plants play an important role in the growth and development, disease resistance, and stress tolerance of the plants; these microorganisms have certain potential for improving the quality of tea. This forum mainly summarizes and discusses the role of microorganisms in regulating tea plants and their prospects for improving the quality of tea.
The double play of a phage HTH regulator
Bacteriophages use anti-CRISPR (Acr) proteins to inhibit CRISPR-Cas systems. The expression of Acr is regulated by anti-CRISPR-associated (Aca) proteins, which are helix-turn-helix (HTH) repressors that bind DNA. Recently, Birkholz et al. discovered that an Aca can also repress Acr expression by binding RNA, revealing a new function for HTH repressors.
Agents of change: a partnership between mobile genetic elements facilitates rapid bacterial adaptation
While the evolutionary interests of mobile genetic elements may differ from those of their bacterial hosts, these elements can be beneficial for their hosts by delivering, disrupting, or activating genes. A recent paper by Sastre-Domínguez et al. describes a novel synergistic effect of mobile elements in clinically relevant bacteria, whereby conjugative plasmids that carry transposable elements can be agents of rapid adaptive change through an elevation in transposition-mediated mutation rate.
From carrion to soil: microbial recycling of animal carcasses
Decomposer microbial communities are gatekeepers in the redistribution of carbon and nutrients from dead animals (carrion) to terrestrial ecosystems. The flush of decomposition products from a carcass creates a hot spot of microbial activity in the soil below, and the animal's microbiome is released into the environment, mixing with soil communities. Changes in soil physicochemistry, especially reduced oxygen, temporarily constrain microbial nutrient cycling, and influence the timing of these processes and the fate of carrion resources. Carcass-related factors, such as mass, tissue composition, or even microbiome composition may also influence the functional assembly and succession of decomposer communities. Understanding these local scale microbially mediated processes is important for predicting consequences of carrion decomposition beyond the hot spot and hot moment.
Diverse molecular mechanisms underpinning Staphylococcus aureus small colony variants
Small colony variants (SCVs) of Staphylococcus aureus are a relatively rare but clinically significant growth morphotype. Infections with SCVs are frequently difficult to treat, inherently antibiotic-resistant, and can lead to persistent infections. Despite a long history of research, the molecular underpinnings of this morphotype and their impact on the clinical trajectory of infections remain unclear. However, a growing body of literature indicates that SCVs are caused by a diverse range of molecular factors. These recent findings suggest that SCVs should be thought of as an ensemble collection of loosely related phenotypes, and not as a single phenomenon. This review describes the diverse mechanisms currently known to contribute to SCVs and proposes an ensemble model for conceptualizing this morphotype.
Loading and unloading plasmid cargoes
Plasmids are vehicles for horizontal gene transfer between cells, but they also exchange genes with associated chromosomes in a process termed 'intracellular mobility'. I discuss a recent article by Kadibalban et al. mapping such plasmid-chromosomal sequence similarities across diverse bacteria.
The role of noncoding RNAs in bacterial immunity
The evolutionary arms race between bacteria and phages has driven the development of diverse anti-phage defense mechanisms. Recent studies have identified noncoding RNAs (ncRNAs) as key players in bacteria-phage conflicts, including CRISPR-Cas, toxin-antitoxin (TA), and reverse transcriptase (RT)-based defenses; however, our understanding of their roles in immunity is still emerging. In this review, we explore the multifaceted roles of ncRNAs in bacterial immunity, offering insights into their contributions to defense and anti-defense mechanisms, their influence on immune regulatory networks, and potential biotechnological applications. Finally, we highlight key outstanding questions in the field to spark future research directions.
A unique bacterial family strikes again!
Garcia et al. recently identified a novel myxobacterial family, Pendulisporaceae, encompassing four strains with novel biosynthetic gene clusters. This study underscores the value of exploring underrepresented microbial taxa for novel natural products, highlighting the potential of the family Pendulisporaceae as a source of new antimicrobial and therapeutic agents.
Tackling coinfections
Mechanistic understanding of the impact of coinfections is a critical knowledge gap. A workshop on coinfections highlighted key aspects required to advance this field, including identifying the coinfection priorities, creating research platforms for this type of research, promoting cross-expertise collaborations, and securing funding to support cross-kingdom pathogen research.
Ancient environmental microbiomes and the cryosphere
In this review, we delineate the unique set of characteristics associated with cryosphere environments (namely, ice and permafrost) which present both challenges and opportunities for studying ancient environmental microbiomes (AEMs). In a field currently reliant on several assumptions, we discuss the theoretical and empirical feasibility of recovering microbial nucleic acids (NAs) from ice and permafrost with varying degrees of antiquity. We also summarize contamination control best practices and highlight considerations for the latest approaches, including shotgun metagenomics, and downstream bioinformatic authentication approaches. We review the adoption of existing software and provide an overview of more recently published programs, with reference to their suitability for AEM studies. Finally, we summarize outstanding challenges and likely future directions for AEM research.
Balancing act: counteracting adverse drug effects on the microbiome
The human gut microbiome, a community of microbes that plays a crucial role in our wellbeing, is highly adaptable but also vulnerable to drug treatments. This vulnerability can have serious consequences for the host, for example, increasing susceptibility to infections, immune, metabolic, and cognitive disorders. However, the microbiome's adaptability also provides opportunities to prevent, protect, or even reverse drug-induced damage. Recently, several innovative approaches have emerged aimed at minimizing the collateral damage of drugs on the microbiome. Here, we outline these approaches, discuss their applicability in different treatment scenarios, highlight current challenges, and suggest avenues that may lead to an effective protection of the microbiome.
Microbial bases of herbivory in beetles
The ecological radiation of herbivorous beetles is among the most successful in the animal kingdom. It coincided with the rise and diversification of flowering plants, requiring beetles to adapt to a nutritionally imbalanced diet enriched in complex polysaccharides and toxic secondary metabolites. In this review, we explore how beetles overcame these challenges by coopting microbial genes, enzymes, and metabolites, through both horizontal gene transfer (HGT) and symbiosis. Recent efforts revealed the functional convergence governing both processes and the unique ways in which microbes continue to shape beetle digestion, development, and defense. The development of genetic and experimental tools across a diverse set of study systems has provided valuable mechanistic insights into how microbes spurred metabolic innovation and facilitated an herbivorous transition in beetles.
Transitioning ecosystems: how will permafrost cryophiles respond to a changing climate?
Permafrost harbours a diversity of cryophilic microorganisms that can be metabolically active at sub-zero temperatures and likely play a role in global carbon cycling. This forum article explores possible impacts of permafrost warming on cold-adapted microbiota, highlights underexplored areas of research, and suggests future short and long-term research foci.
Environmental microbiome, human fungal pathogens, and antimicrobial resistance
Traditionally, antifungal resistance (AFR) has received much less attention compared with bacterial resistance to antibiotics. However, global changes, pandemics, and emerging new fungal infections have highlighted global health consequences of AFR. The recent report of the World Health Organisation (WHO) has identified fungal priority pathogens, and recognised AFR among the greatest global health threats. This is particularly important given the significant increase in fungal infections linked to climate change and pandemics. Environmental factors play critical roles in AFR and fungal infections, as many clinically relevant fungal pathogens and AFR originate from the environment (mainly soil). In addition, the environment serves as a potential rich source for the discovery of new antifungal agents, including mycoviruses and bacterial probiotics, which hold promise for effective therapies. In this article, we summarise the environmental pathways of AFR development and spread among high priority fungal pathogens, and propose potential mechanisms of AFR development and spread. We identify a research priority list to address key knowledge gaps in our understanding of environmental AFR. Further, we propose an integrated roadmap for predictive risk management of AFR that is critical for effective surveillance and forecasting of public health outcomes under current and future climatic conditions.