Tim B. Schille, Jakob L. Sprague, Julian R. Naglik, Sascha Brunke, Bernhard Hube
{"title":"Commensalism and pathogenesis of Candida albicans at the mucosal interface","authors":"Tim B. Schille, Jakob L. Sprague, Julian R. Naglik, Sascha Brunke, Bernhard Hube","doi":"10.1038/s41579-025-01174-x","DOIUrl":"10.1038/s41579-025-01174-x","url":null,"abstract":"Fungi are important and often underestimated human pathogens. Infections with fungi mostly originate from the environment, from soil or airborne spores. By contrast, Candida albicans, one of the most common and clinically important fungal pathogens, permanently exists in the vast majority of healthy individuals as a member of the human mucosal microbiota. Only under certain circumstances will these commensals cause infections. However, although the pathogenic behaviour and disease manifestation of C. albicans have been at the centre of research for many years, its asymptomatic colonization of mucosal surfaces remains surprisingly understudied. In this Review, we discuss the interplay of the fungus, the host and the microbiome on the dualism of commensal and pathogenic life of C. albicans, and how commensal growth is controlled and permitted. We explore hypotheses that could explain how the mucosal environment shapes C. albicans adaptations to its commensal lifestyle, while still maintaining or even increasing its pathogenic potential. In this Review, Hube and colleagues overview the commensal and pathogenic lifestyles of Candida albicans, focusing on how the fungus transitions between these two states, the fungal and host factors involved, and the role of the mucosal microbiota on C. albicans commensalism.","PeriodicalId":18838,"journal":{"name":"Nature Reviews Microbiology","volume":"23 8","pages":"525-540"},"PeriodicalIF":103.3,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Lassoing bacterial ribosomes","authors":"Andrea Du Toit","doi":"10.1038/s41579-025-01182-x","DOIUrl":"10.1038/s41579-025-01182-x","url":null,"abstract":"This study reports the identification of a ribosome-targeting lasso peptide that acts on a new ribosomal binding site.","PeriodicalId":18838,"journal":{"name":"Nature Reviews Microbiology","volume":"23 6","pages":"335-335"},"PeriodicalIF":103.3,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Growing together under pressure","authors":"Andrea Du Toit","doi":"10.1038/s41579-025-01184-9","DOIUrl":"10.1038/s41579-025-01184-9","url":null,"abstract":"This study shows that mechanical pressure induces multicellular development in Haloferax volcanii.","PeriodicalId":18838,"journal":{"name":"Nature Reviews Microbiology","volume":"23 6","pages":"335-335"},"PeriodicalIF":103.3,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The global resistance problem and the clinical antibacterial pipeline","authors":"Ursula Theuretzbacher","doi":"10.1038/s41579-025-01169-8","DOIUrl":"10.1038/s41579-025-01169-8","url":null,"abstract":"A comprehensive analysis of the clinical antibacterial pipeline demonstrates that there is a limited range of strategies that are primarily focused on modified versions of widely used chemical classes. These modifications aim to circumvent class-specific resistance mechanisms and reduce resistance rates in certain multidrug-resistant pathogens. Owing to the great variation in resistance rates and mechanisms, the clinical success of current approaches varies substantially across different countries, regions, and economic and environmental conditions, which affects the global societal value of these antibiotics that remain vulnerable to cross-resistance. Although there has been some progress in developing urgently needed antibiotics with novel targets and chemical structures, some of which have advanced to phase I/II trials, further breakthroughs are required. Additionally, adjunctive agents designed to enhance the outcome of conventional antibiotic therapies, along with bacteriophages that offer targeted and personalized treatments, are also under investigation. However, the potential of adjunctive therapeutics, such as antivirulence agents, and bacteriophages has yet to be realized in terms of feasibility and global societal impact. In this Review, Theuretzbacher explores current clinical antibacterial agents in clinical development, incorporating global health considerations and the need for effective, accessible therapies worldwide.","PeriodicalId":18838,"journal":{"name":"Nature Reviews Microbiology","volume":"23 8","pages":"491-508"},"PeriodicalIF":103.3,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143813665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cellular souvenirs in viral luggage","authors":"Yumary M. Vasquez","doi":"10.1038/s41579-025-01179-6","DOIUrl":"10.1038/s41579-025-01179-6","url":null,"abstract":"This Genome Watch article highlights recent findings of cellular-like genes in giant viruses and how these viruses acquire and repurpose host cellular machinery.","PeriodicalId":18838,"journal":{"name":"Nature Reviews Microbiology","volume":"23 7","pages":"409-409"},"PeriodicalIF":103.3,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143813668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A new strain of thought in gut metagenomics","authors":"Bonface M. Gichuki, Andrew G. Van Camp, Yan Shao","doi":"10.1038/s41579-025-01176-9","DOIUrl":"10.1038/s41579-025-01176-9","url":null,"abstract":"This Genome Watch discusses advancements in our understanding of interpersonal transmission dynamics of the human gut microbiota and their implications for host health and therapeutic outcomes.","PeriodicalId":18838,"journal":{"name":"Nature Reviews Microbiology","volume":"23 6","pages":"337-337"},"PeriodicalIF":103.3,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143758171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Martin Kaltenpoth, Laura V. Flórez, Aurélien Vigneron, Philipp Dirksen, Tobias Engl
{"title":"Origin and function of beneficial bacterial symbioses in insects","authors":"Martin Kaltenpoth, Laura V. Flórez, Aurélien Vigneron, Philipp Dirksen, Tobias Engl","doi":"10.1038/s41579-025-01164-z","DOIUrl":"10.1038/s41579-025-01164-z","url":null,"abstract":"Beneficial bacterial symbionts are widespread in insects and affect the fitness of their hosts by contributing to nutrition, digestion, detoxification, communication or protection from abiotic stressors or natural enemies. Decades of research have formed our understanding of the identity, localization and functional benefits of insect symbionts, and the increasing availability of genome sequences spanning a diversity of pathogens and beneficial bacteria now enables comparative approaches of their metabolic features and their phylogenetic affiliations, shedding new light on the origin and function of beneficial symbioses in insects. In this Review, we explore the symbionts’ metabolic traits that can provide benefits to insect hosts and discuss the evolutionary paths to the formation of host-beneficial symbiotic associations. Phylogenetic analyses and molecular studies reveal that extracellular symbioses colonizing cuticular organs or the digestive tract evolved from a broad diversity of bacterial partners, whereas intracellular beneficial symbionts appear to be restricted to a limited number of lineages within the Gram-negative bacteria and probably originated from parasitic ancestors. To unravel the general principles underlying host–symbiont interactions and recapitulate the early evolutionary steps leading towards beneficial symbioses, future efforts should aim to establish more symbiotic systems that are amenable to genetic manipulation and experimental evolution. In this Review, Kaltenpoth et al. examine the evolution and function of beneficial symbioses between bacteria and their insect hosts, focusing on their effects on the host fitness and the microbial factors that play a role in the evolution of these symbiotic associations.","PeriodicalId":18838,"journal":{"name":"Nature Reviews Microbiology","volume":"23 9","pages":"551-567"},"PeriodicalIF":103.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143712975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
José R. Penadés, Kimberley D. Seed, John Chen, David Bikard, Eduardo P. C. Rocha
{"title":"Genetics, ecology and evolution of phage satellites","authors":"José R. Penadés, Kimberley D. Seed, John Chen, David Bikard, Eduardo P. C. Rocha","doi":"10.1038/s41579-025-01156-z","DOIUrl":"10.1038/s41579-025-01156-z","url":null,"abstract":"Phage satellites are defined as viruses that have a life cycle dependent on a helper virus. Thus, they are often considered as parasites of parasites, although recent work suggests it may be more accurate to consider them as symbionts that evolved along a parasitism–mutualism continuum. Over the past years, multiple studies have examined the fascinating life cycle of these elements, focusing on the characterization of the molecular mechanisms they use to hijack the helper phage machinery for their own packaging and transfer. As some phage satellites encode toxins and other virulence and resistance genes, the impact of these elements on bacterial virulence has also been extensively analysed. Recent studies suggest that satellites have unprecedented roles in the ecology and evolution of bacteria and their mobile genetic elements. In this Review, we explore the genetics and the life cycle of these elements, with special emphasis on the new mechanisms involved in their spread in nature. We discuss the unexpected impact of these elements on the evolution of other mobile genetic elements and their host bacteria, and examine their potential origins. In this Review, Penadés et al. explore the genetics, potential origins and life cycle of phage satellites, and they discuss the impact of these elements on the evolution of other mobile genetic elements and their host bacteria.","PeriodicalId":18838,"journal":{"name":"Nature Reviews Microbiology","volume":"23 7","pages":"410-422"},"PeriodicalIF":103.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143712977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ursula Theuretzbacher, Ravindra P. Jumde, Alan Hennessy, Jennifer Cohn, Laura J. V. Piddock
{"title":"Global health perspectives on antibacterial drug discovery and the preclinical pipeline","authors":"Ursula Theuretzbacher, Ravindra P. Jumde, Alan Hennessy, Jennifer Cohn, Laura J. V. Piddock","doi":"10.1038/s41579-025-01167-w","DOIUrl":"10.1038/s41579-025-01167-w","url":null,"abstract":"Antibacterial resistance is a global challenge that requires a coordinated international response. The current clinical pipeline largely consists of derivatives of established antibiotic classes, whereas the discovery and preclinical pipeline is diverse and innovative including new direct-acting agents with no cross-resistance with existing antibiotics. These novel compounds target pathways such as lipoprotein synthesis, lipopolysaccharide biosynthesis and transport, outer membrane assembly, peptidoglycan biosynthesis, fatty acid biosynthesis and isoprenoid biosynthesis. If these agents can be developed into safe, effective and affordable drugs, they could address a broad range of infections worldwide, benefiting large patient populations without geographical limitations. However, strategies such as indirect-acting or pathogen-specific treatments are likely to benefit small patient groups, primarily in high-income countries that have advanced health-care systems and diagnostic infrastructure. Although encouraging, the discovery and preclinical pipeline remains insufficiently robust to offset the high attrition rates typical of early-stage drug innovation and to meet global health needs. Piddock and colleagues explore new antibacterial compounds in active late discovery phase and preclinical development focusing on innovative strategies, with a global health perspective.","PeriodicalId":18838,"journal":{"name":"Nature Reviews Microbiology","volume":"23 8","pages":"474-490"},"PeriodicalIF":103.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143712976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Galo A. Goig, Etthel M. Windels, Chloé Loiseau, Christoph Stritt, Loza Biru, Sonia Borrell, Daniela Brites, Sebastien Gagneux
{"title":"Ecology, global diversity and evolutionary mechanisms in the Mycobacterium tuberculosis complex","authors":"Galo A. Goig, Etthel M. Windels, Chloé Loiseau, Christoph Stritt, Loza Biru, Sonia Borrell, Daniela Brites, Sebastien Gagneux","doi":"10.1038/s41579-025-01159-w","DOIUrl":"10.1038/s41579-025-01159-w","url":null,"abstract":"With the COVID-19 pandemic receding, tuberculosis (TB) is again the number one cause of human death to a single infectious agent. TB is caused by bacteria that belong to the Mycobacterium tuberculosis complex (MTBC). Recent advances in genome sequencing have provided new insights into the ecology and evolution of the MTBC. This includes the discovery of new phylogenetic lineages within the MTBC, a deeper understanding of the host tropism among the various animal-adapted lineages, enhanced knowledge on the evolutionary dynamics of antimicrobial resistance and transmission, as well as a better grasp of the within-host MTBC diversity. Moreover, advances in long-read sequencing are increasingly highlighting the relevance of structural genomic variation in the MTBC. These findings not only shed new light on the biology and epidemiology of TB, but also give rise to new questions and research avenues. The purpose of this Review is to summarize these new insights and discuss their implications for global TB control. In this Review, Gagneux and colleagues discuss ecological and evolutionary concepts related to the biology and epidemiology of the Mycobacterium tuberculosis complex, including new phylogenetic lineages, host tropism among the various animal-adapted lineages, the evolutionary dynamics of antimicrobial resistance and transmission, as well as within-host diversity and structural genomic variation.","PeriodicalId":18838,"journal":{"name":"Nature Reviews Microbiology","volume":"23 9","pages":"602-614"},"PeriodicalIF":103.3,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143695669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}