Current opinion in microbiology最新文献

Predicting the evolution of antibiotic resistance is critical for realizing precision antibiotic therapies. How exactly to achieve such predictions is a theoretical challenge. Insights from mathematical models that reflect future behavior of microbes under antibiotic stress can inform intervention protocols. However, this requires going beyond heuristic approaches by modeling ecological and evolutionary responses linked to metabolic pathways and cellular functions. Developing such models is now becoming possible due to increasing data availability from systematic experiments with microbial systems. Here, I review recent theoretical advances promising building blocks to piece together a predictive theory of antibiotic resistance evolution. I focus on the conceptual framework of eco-evolutionary response models grounded on quantitative laws of bacterial physiology. These forward-looking models can predict previously unknown behavior of bacteria upon antibiotic exposure. With current developments covering mostly the case of ribosome-targeting antibiotics, I write this Opinion piece as an invitation to generalize the principles discussed here to a broader range of drugs and context dependencies.

The bacterial stressosome is a supramolecular multiprotein complex that acts as a critical signal integration and transduction hub, orchestrating cellular responses to environmental stimuli. Recent studies have resolved near-atomic stressosome structures from various bacterial species, revealing assemblies that should be capable of altering their configuration in response to external changes. Further genetic, biochemical, and cell biology research has elucidated interactions and phosphorylation status within the stressosome complex as well as its subcellular localization and mobility within living cells. These insights enhance our comprehension of the stressosome pathways and their roles in directing various survival responses during environmental stress.

Improved understanding of the human fungal pathogen Cryptococcus neoformans, classically described as a basidiomycete budding yeast, has revealed new infection-relevant single cell morphologies in vivo and in vitro. Here, we ask whether these morphologies constitute true morphotypes, requiring updated classification of C. neoformans as a pleomorphic fungus. We profile recent discoveries of C. neoformans seed cells and titan cells and provide a framework for determining whether these and other recently described single-cell morphologies constitute true morphotypes. We demonstrate that multiple C. neoformans single-cell morphologies are transcriptionally distinct, stable, heritable, and associated with active growth and therefore should be considered true morphotypes in line with the classification in other well-studied fungi. We conclude that C. neoformans is a pleomorphic fungus with an important capacity for morphotype switching that underpins pathogenesis.

Although our understanding of both bacterial cell physiology and the complex behaviors exhibited by bacterial biofilms is expanding rapidly, we cannot yet sum the behaviors of individual cells to understand or predict biofilm behavior. This is both because cell physiology in biofilms is different from planktonic growth and because cell behavior in biofilms is spatiotemporally patterned. We use developmental biology as a guide to examine this phenotypic patterning, discussing candidate cues that may encode spatiotemporal information and possible roles for phenotypic patterning in biofilms. We consider other questions that arise from the comparison between biofilm and eukaryotic development, including what defines normal biofilm development and the nature of biofilm cell types and fates. We conclude by discussing what biofilm development can tell us about developmental processes, emphasizing the additional challenges faced by bacteria in biofilm development compared with their eukaryotic counterparts.

The cell envelope is at the center of many processes essential for bacterial lifestyles. In addition to giving bacteria shape and delineating it from the environment, it contains macromolecules important for energy transduction, cell division, protection against toxins, biofilm formation, or virulence. Hence, many systems coordinate different processes within the cell envelope to ensure function and integrity. Two-component systems have been identified as crucial regulators of cell envelope functions over the last few years. In this review, we summarize the new information obtained on the regulation of cell envelope biosynthesis and homeostasis in α-proteobacteria, as well as newly identified targets that coordinate the processes in the cell envelope.

RNA polymerase (RNAP), the central enzyme of transcription, intermittently pauses during the elongation stage of RNA synthesis. Pausing provides an opportunity for regulatory events such as nascent RNA folding or the recruitment of transregulators. NusG (Spt5 in eukaryotes and archaea) regulates RNAP pausing and is the only transcription factor conserved across all cellular life. NusG is a multifunctional protein: its N-terminal domain (NGN) binds to RNAP, and its C-terminal KOW domain in bacteria interacts with transcription regulators such as ribosomes and termination factors. In Escherichia coli, NusG acts as an antipausing factor. However, recent studies have revealed that NusG has distinct transcriptional regulatory roles specific to bacterial clades with clinical implications. Here, we focus on NusG’s dual roles in the regulation of pausing.

Bacteria thrive in diverse environments and must withstand various stresses. A key stress response mechanism is the reprogramming of macromolecular biosynthesis and metabolic processes through alarmones — signaling nucleotides that accumulate intracellularly in response to metabolic stress. Diadenosine tetraphosphate (Ap4A), a putative alarmone, is produced in a noncanonical reaction by universally conserved aminoacyl-tRNA synthetases. Ap4A is ubiquitous across all domains of life and accumulates during heat and oxidative stress. Despite its early discovery in 1966, Ap4A’s alarmone status remained inconclusive. Recent discoveries identified Ap4A as a precursor to RNA 5′ caps in Escherichia coli. Additionally, Ap4A was found to directly bind to and allosterically inhibit the purine biosynthesis enzyme inosine 5′-monophosphate dehydrogenase, regulating guanosine triphosphate levels and enabling heat resistance in Bacillus subtilis. These findings, along with previous research, strongly suggest that Ap4A plays a crucial role as an alarmone, warranting further investigation to fully elucidate its functions.

Membrane vesicles (MVs) are produced in all domains of life. In eukaryotes, extracellular vesicles have been shown to mediate the horizontal transfer of biological material between cells [1]. Therefore, bacterial MVs are also thought to mediate horizontal material transfer to host cells and other bacteria, especially in the context of cell stress. In this review, we discuss the mechanisms of bacterial MV production, evidence that their contents can be trafficked to host cells and other bacteria, and the biological relevance of horizontal material transfer by bacterial MVs.

Fungal effector proteins function at the interfaces of diverse interactions between fungi and their plant and animal hosts, facilitating interactions that are pathogenic or mutualistic. Recent advancements in protein structure prediction have significantly accelerated the identification and functional predictions of these rapidly evolving effector proteins. This development enables scientists to generate testable hypotheses for functional validation using experimental approaches. Research frontiers in effector biology include understanding pathways through which effector proteins are secreted or translocated into host cells, their roles in manipulating host microbiomes, and their contribution to interacting with host immunity. Comparative effector repertoires among different fungal–host interactions can highlight unique adaptations, providing insights for the development of novel antifungal therapies and biocontrol strategies.

D-galactonate, a widely prevalent sugar acid, was first reported as a nutrient source for enteric bacteria in the 1970s. Since then, decades of research enabled a description of the modified Entner-Doudoroff pathway involved in its degradation and reported the structural and biochemical features of its metabolic enzymes, primarily in Escherichia coli K-12. However, only in the last few years, the D-galactonate transporter has been characterized, and the regulation of the dgo operon, encoding the structural genes for the transporter and enzymes of D-galactonate metabolism, has been detailed. Notably, in recent years, multiple evolutionary studies have identified the dgo operon as a dominant target for adaptation of E. coli in the mammalian gut. Despite considerable research on dgo operon, numerous fundamental questions remain to be addressed. The emerging relevance of the dgo operon in host–bacterial interactions further necessitates the study of D-galactonate metabolism in other enterobacterial strains.