Annual review of microbiology最新文献

Apicomplexan and trypanosomatid parasites cause important human diseases, including malaria, toxoplasmosis, Chagas disease, and human leishmaniasis. The mammalian-infective stages of these parasites colonize nutrient-rich, intracellular niches in a range of different host cells. These niches include specialized vacuoles (Plasmodium spp., Toxoplasma gondii), the mature lysosome of phagocytic cells (Leishmania), and the cytoplasm of nucleated host cells (Trypanosoma cruzi). Here, we review the different growth and metabolic strategies utilized by each of these protists to survive in these niches. Although all stages utilize sugars as preferred carbon sources, different species or developmental stages vary markedly in their dependence on aerobic fermentation versus respiratory metabolism and their co-utilization of other carbon sources. Stage-specific differences in glycolytic and mitochondrial respiratory capacity may be a hardwired feature of each stage and reflect the trade-off of achieving high growth rates at the expense of host range adaptability and establishing long-lived persistent infections.

Opportunistic fungal infections are a major cause of morbidity and mortality in sub-Saharan Africa. The high prevalence of advanced HIV disease, limited surveillance and reporting of fungal disease, and lack of access to healthcare lead to a disproportionate number of fungal-related deaths in this region. This review explores selected fungal pathogens associated with the highest mortality rates: Cryptococcus neoformans and Pneumocystis jirovecii, as well as endemic dimorphic fungal pathogens Histoplasma spp. and Emergomyces africanus, which are underreported in the region. Recent advances in our understanding of pathogenesis and how this knowledge may be exploited for the development of novel antifungals and therapies are discussed. We reflect on the risk factors unique to sub-Saharan Africa and on the diagnostic and treatment challenges, and we highlight the current research priorities that are needed to reduce the burden of fungal disease in this endemic region.

My time in science spans the period from the early 1960s to the present and has enabled me to experience science from the dawn of molecular biology to our current time of rapid technological advancement and knowledge explosion. I have also been privileged to be a part of the great democratization of science. I tell the story of this impactful time in science and society from the perspective of my personal and professional journey, starting from Lac repressor studies, progressing to studying bacterial transcription (most especially the "σ universe"), and now centering on the development and use of global technologies to solve the huge genotype-phenotype gap: how to acquire in years, not decades, gene function and pathway information in understudied organisms critical to human and planetary health. The scientific explosion I have witnessed also suggests that the potential for science to positively influence our world has never been higher.

The characterization of the human microbiome has opened a new chapter in understanding human biology and its relationship to health and disease. Yet we also have learned that our ancient coevolved microbiome has been changing across recent human generations; we have been losing a substantial amount of its diversity. This is especially concerning because the microbiota that we acquire early in life has important bearing on our developmental trajectory, especially with regard to metabolism, immunity, and cognition. Collectively, the early-life microbiota is a partner in our human developmental biology. We detail the medical, public health, and dietary phenomena bearing on the acquisition, maintenance, and loss of members of the microbiota and then consider the linkages between the altered microbiome and the diseases that have been emerging in recent years. Finally, we highlight ways to address and solve these problems associated with modernization.

Over billions of years, marine microorganisms evolved a vast genetic potential to produce the molecules we denote as natural products or secondary metabolites. While these molecules show promise as therapeutics, their ecological roles, beyond those as antimicrobials, are receiving increasing attention. This review examines recent advances in our understanding of the ecological functions of marine microbial natural products and highlights both known and emerging roles. We summarize the involvement of these natural products in biological, ecological, and biogeochemical processes in the oceans; outline how their production may profoundly affect the producing organism; and discuss how the presence of natural product-producing microorganisms may affect microbiome composition and function. Despite progress, knowledge about the ecological roles of marine microbial natural products remains limited, and we also discuss challenges and opportunities in this field, including promising new technologies that could provide novel insights.

Bacteria of the phylum Actinomycetota are extremely diverse: They inhabit niches ranging from soils and ocean sediments to the normal human microbiota, and they cause tuberculosis, one of the most prevalent chronic bacterial infections. They display an accordingly wide range of adaptive traits that enable their persistence, including, in some clades, a vast repertoire of biologically active small molecules. While humans have capitalized on this trove of useful natural products (also called secondary or specialized metabolites), the utility of these molecules for their producers has been challenging to directly assess. In this review, we consider adaptations that may have paved the way for the evolution of the expansive specialized metabolisms present in certain clades of Actinomycetota. We also consider the evolutionary pressures that may have driven diversification of these metabolisms and document how these organisms use these molecules in microbial interactions.

Purines are ubiquitous metabolites that play evolutionarily conserved roles, including as precursors to molecules central to life. Purine synthesis is metabolically and energetically expensive; thus, under physiological conditions, intermediates of purine degradation are efficiently reused through salvage pathways. Excess purines are oxidized and eliminated via the kidneys and intestine. The efficient elimination of excess purines in humans is critical because the primary waste product of purine metabolism, uric acid, is proinflammatory and has been linked to multiple health conditions. Recent studies suggest that gut bacteria influence the purine pool locally and systemically. Bacteria can break down uric acid and other purines aerobically and anaerobically and may regulate their homeostasis. In this article, we provide an overview of purines and their metabolism, and we discuss our current understanding of the complex purine-dependent cross talk and cross-feeding between the host and the gut microbiome.

Plant biomass has emerged as a cornerstone of the global bioenergy landscape because of its abundance and cost-effectiveness. The cell wall of plant biomass is an intricate network of cellulose, hemicellulose, and lignin. The hydrolysis of cellulose and hemicellulose by holoenzymes converts these polymers into monosaccharides and paves the way for the production of bioethanol and other bio-based products. This enzymatic and fermentative process is crucial for the sustainable use of agro-industrial residues as renewable energy sources, reducing reliance on fossil fuels and lowering greenhouse gas emissions. This review explores critical aspects of lignocellulolytic enzyme systems, all of which derive from microorganisms. Furthermore, it underscores the advantages of microbial sources and their potential for enhancing enzyme properties through genetic engineering and enzyme immobilization.

Drosophila fruit flies are a powerful model for studying innate immunity. In Drosophila, seven classical antimicrobial peptide (AMP) gene families were identified in the 1990s. These genes are primarily regulated by the TOLL and IMD NF-κB pathways in response to infection. Analyses of mutants have revealed their important roles, including a surprising degree of peptide-microbe specificity at the effector level, in the host defense against gram-negative bacteria and fungi. Many new families of host defense peptides (HDPs) with unknown mechanisms of action are now being investigated. One prominent example is the Bomanins, which are peptides with an essential role in combatting infection by practically all gram-positive bacteria and fungi. Recent studies suggest that AMPs may have broader roles beyond direct antimicrobial activity, notably in the brain and behavior. This review summarizes what is known about each family of Drosophila HDPs and provides supplementary discussion for less characterized genes involved in defense against infection.

Circadian rhythms play a fundamental role in regulating biological processes across the tree of life. While these 24-h cycles are well-characterized in model organisms, their role in parasitic organisms has remained largely unexplored until recently. Here, we review emerging evidence that parasites possess intrinsic timekeeping abilities, focusing particularly on the malaria parasite Plasmodium. We examine two principal paradigms of biological timing: transcriptional-translational feedback loops and posttranscriptional feedback loops. Despite lacking canonical clock genes found in other eukaryotes, Plasmodium employs sophisticated regulatory machinery, including ApiAP2 transcription factors, chromatin regulators, and noncoding RNAs, that could form novel timing circuits. We discuss how these mechanisms might enable parasites to synchronize with host rhythms and optimize their development and transmission. Understanding these temporal regulatory networks could reveal new therapeutic strategies and expand our knowledge of biological timing mechanisms across evolution.