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.