{"title":"Recent advances in natural and synthetic phosphonate therapeutics","authors":"Jerry Cui , Kou-San Ju","doi":"10.1016/j.mib.2025.102630","DOIUrl":"10.1016/j.mib.2025.102630","url":null,"abstract":"<div><div>Phosphonate and phosphinate compounds — both natural and synthetic — have given rise to major families of therapeutics and agricultural agents. The antibiotic fosfomycin, the antivirals foscarnet and tenofovir, the bisphosphonates, and the herbicides phosphinothricin and glyphosate all belong to this compound class. The carbon–phosphorus bonds that define these molecules enable chemical mimicry of essential phosphate ester and carboxylate metabolites within metabolism, which is the foundation for their bioactivity. Here, we review examples of C-P compounds in drug discovery. In the first half, we highlight the ongoing development of two phosphonate natural products, both of which were initially discovered as antibiotics: fosmidomycin, which has undergone clinical trials as an antimalarial, and SF-2312, derivatives of which are currently being explored as chemotherapeutics. In the second half, we summarize how the C-P moiety has inspired chemical synthesis of new antimicrobials, immunomodulators, and targeted protein degradation agents.</div></div>","PeriodicalId":10921,"journal":{"name":"Current opinion in microbiology","volume":"87 ","pages":"Article 102630"},"PeriodicalIF":5.9,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144604198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Laura Rodriguez-Velandia , Ethan A Older , Laura M Sanchez
{"title":"Seeing between the lines: matrix-assisted laser desorption/ionization mass spectrometry imaging advances for microbial interactions","authors":"Laura Rodriguez-Velandia , Ethan A Older , Laura M Sanchez","doi":"10.1016/j.mib.2025.102634","DOIUrl":"10.1016/j.mib.2025.102634","url":null,"abstract":"<div><div>This review delves into the technical advancements of matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) applications from the last 15 years, highlighting its importance as an analytical tool for exploring the complex interactions within microbial communities. Recognizing the limitations of standard laboratory cultivation practices, we examine how recent research has worked toward bridging the gap between controlled laboratory experiments and <em>in situ</em> measurements. We discuss the shift from traditional agar-based co-culture to newer methods, such as 3D MALDI-MSI and artificial environments, ultimately progressing toward <em>in situ</em> analysis. We highlight the innovative aspects of these methodologies, emphasizing the technical challenges of sample preparation and subsequent metabolite identification. While MALDI-MSI has proven to be an invaluable tool for mapping chemical communication within complex microbial communities, we acknowledge the significant bottlenecks that remain. We call on the researchers to use establish reporting standards and support the expansion of metabolomic databases for future discoveries.</div></div>","PeriodicalId":10921,"journal":{"name":"Current opinion in microbiology","volume":"87 ","pages":"Article 102634"},"PeriodicalIF":5.9,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144604199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pingzhuang Ge , Fatema-Zahra M Rashid , Remus T Dame
{"title":"The role of nucleoid-associated proteins in mediating responses to environmental changes","authors":"Pingzhuang Ge , Fatema-Zahra M Rashid , Remus T Dame","doi":"10.1016/j.mib.2025.102628","DOIUrl":"10.1016/j.mib.2025.102628","url":null,"abstract":"<div><div>Bacteria face diverse environmental challenges, such as changes in temperature, pH, and osmolarity, and exposure to antibiotics, which necessitate adaptive responses for survival. The chromosome-structuring nucleoid-associated proteins (NAPs) are key to these responses owing to their role in global gene regulation. In this review, we summarize the functional interplay between environmental challenges and NAPs, and the adaptive responses mediated by NAPs. Specifically, physicochemical environmental factors modify the transcription level of NAP genes and affect protein activity, which facilitates bacterial adaptation via a short-term strategy. Additionally, NAPs regulate horizontally transferred genes, such as those involved in antibiotic resistance and virulence, by affecting their expression and integration into the host genome. Via this long-term strategy, NAPs contribute to both stress resilience and the evolution of bacterial traits, ensuring survival under environmental stress while facilitating genetic diversity through horizontal gene transfer.</div></div>","PeriodicalId":10921,"journal":{"name":"Current opinion in microbiology","volume":"87 ","pages":"Article 102628"},"PeriodicalIF":5.9,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144588508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Swimming or sessile: the interplay between c-di-GMP signalling and flagellar motility","authors":"Xuanlin Chen, Liyun Wang, Victor Sourjik","doi":"10.1016/j.mib.2025.102632","DOIUrl":"10.1016/j.mib.2025.102632","url":null,"abstract":"<div><div>Bacteria have evolved multiple strategies to thrive in diverse environments. These include the ability to make rapid transitions between motile and sessile lifestyles, either of which might be favoured dependent of the environmental conditions. The central regulator for these lifestyle transitions is the second messenger cyclic dimeric guanosine monophosphate (c-di-GMP), which in general, inhibits flagellar motility and promotes the formation of sessile biofilm communities. Reciprocally, flagellated cells suppress c-di-GMP synthesis or activate its degradation to preserve motility. The interplay between c-di-GMP signalling and motility occurs at multiple levels of regulation, with evolutionarily conserved general principles but species-specific molecular mechanisms enabling environmental adaptations. Recent studies, described in this review, have revealed the emergent complexity of the intricate cross-regulation between c-di-GMP signalling and flagellar motility, highlighting context-specific deviations from simple antagonism and underscoring the importance of studying transient dynamics of c-di-GMP, gene expression, and motility changes during the lifestyle transitions.</div></div>","PeriodicalId":10921,"journal":{"name":"Current opinion in microbiology","volume":"87 ","pages":"Article 102632"},"PeriodicalIF":5.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144588506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Olga Iwańska, Przemysław Latoch, Agata L. Starosta
{"title":"Compartmentalization during bacterial spore formation","authors":"Olga Iwańska, Przemysław Latoch, Agata L. Starosta","doi":"10.1016/j.mib.2025.102633","DOIUrl":"10.1016/j.mib.2025.102633","url":null,"abstract":"<div><div>Here, we explore the recent advancements in understanding cellular compartmentalization during bacterial spore formation, primarily focusing on the model organism <em>Bacillus subtilis</em>. The hallmark of sporulation, asymmetric septation, physically separates the mother cell and forespore, enabling distinct developmental fates. We highlight the role of the asymmetric septum as an organizational hub coordinating diverse compartmentalized functions — from gene regulation to metabolism and protein synthesis machinery localization.</div><div>Asymmetric septation involves precise positioning of the division machinery, chromosome segregation, and septal pore formation. Recent studies have revealed detailed structure of the asymmetric septum and its role in maintaining compartment integrity, especially through interactions involving SpoIIE, SpoIIIE, peptidoglycan remodeling enzymes (like the SpoIIDMP complex), and the SpoIIIA-SpoIIQ channel. The asymmetric septum also plays a role in the spatiotemporal localization of ribosomes, with their entry into the forespore being coupled to septal peptidoglycan remodeling. This observation not only demonstrates translational compartmentalization during sporulation but also reveals the uncoupling of transcription and translation processes in <em>B. subtilis</em>. Moreover, the mother cell and forespore establish distinct metabolic roles, as the mother cell supplies essential metabolites to the forespore through the SpoIIIA-SpoIIQ feeding tube channel, supporting the synthesis of the spore structural components necessary for spore maturation.</div><div>Advanced imaging techniques and multi-omics approaches have significantly enhanced our understanding of compartmentalization during sporulation. We conclude by discussing future research directions, including the application of machine learning approaches, expansion of research to nonmodel bacterial species, and exploration of evolutionary aspects of compartmentalization, which may reveal universal mechanisms of microbial organization.</div></div>","PeriodicalId":10921,"journal":{"name":"Current opinion in microbiology","volume":"87 ","pages":"Article 102633"},"PeriodicalIF":5.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144588507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Encapsulins: catalysis inside a shell","authors":"Asif Fazal, Tobias W Giessen","doi":"10.1016/j.mib.2025.102629","DOIUrl":"10.1016/j.mib.2025.102629","url":null,"abstract":"<div><div>Internal cellular organization is a defining feature of life, and encapsulins are an effective, protein-based method for prokaryotic cells to achieve compartmentalization of chemical reactions and metabolic processes. The defining feature of encapsulins is their ability to encapsulate cargo proteins inside a self-assembling protein shell, mediated by cargo-encoded targeting peptides or domains. The biochemical and physiological function of an encapsulin system is dictated by the catalytic activity of encapsulated components, with the protein shell acting as a selectively permeable diffusion barrier. Encapsulating cargo proteins confers multiple advantages, including enhanced stability, increased activity, regulatory control, and sequestration of reactive intermediates or reaction products. Encapsulin-cargo systems have key functions in elemental homeostasis, storage, stress resistance, and varied anabolic pathways. This review will focus on the so far characterized cargo proteins encapsulated within encapsulin shells, specifically their catalytic mechanisms and the particular reasons and benefits for protein encapsulation.</div></div>","PeriodicalId":10921,"journal":{"name":"Current opinion in microbiology","volume":"86 ","pages":"Article 102629"},"PeriodicalIF":5.9,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144557019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A tale of two nitrous oxide reductases: a cautionary perspective","authors":"Sukhwan Yoon , Min Joon Song , Michele Laureni","doi":"10.1016/j.mib.2025.102631","DOIUrl":"10.1016/j.mib.2025.102631","url":null,"abstract":"<div><div>Nitrous oxide reductases (N2OR) are the sole sink of the potent greenhouse gas nitrous oxide (N<sub>2</sub>O) in the environment. Having been studied for decades, N2OR have attracted renewed attention following the discovery of a previously unrecognized clade, now termed clade II. This clade exhibits unexpectedly widespread taxonomic distribution and prevalence across diverse environments, prompting research efforts to define and assign distinct clade-specific traits. In this perspective, we aim to critically review and evaluate dichotomous clade-based classifications, addressing oversimplifications and unresolved ambiguities in linking clade identity to physiological traits like substrate affinity, acid tolerance, and aerotolerance. Growing experimental evidence from N<sub>2</sub>O-reducing isolates and enrichments suggests a general difference in substrate affinity between the clades. Recent discoveries of N<sub>2</sub>O reduction at pH < 5.0 attribute the long-sought acidophilic N<sub>2</sub>O reduction exclusively to organisms possessing clade II <em>nosZ</em>, and attempts have also been made to relate clade separation to aerotolerant N<sub>2</sub>O reduction. However, it is important to note that such binary characterizations are based on limited observations and lack a solid understanding of the underlying mechanisms, exposing them to bias and oversimplification risks. We emphasize the need for a balanced research effort to establish a robust link between ecophysiology and biochemistry, enabling a more accurate evaluation of clade-based characterizations and, ultimately, a deeper understanding and effective harnessing of N<sub>2</sub>O-reducing organisms.</div></div>","PeriodicalId":10921,"journal":{"name":"Current opinion in microbiology","volume":"86 ","pages":"Article 102631"},"PeriodicalIF":5.9,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144557020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Skin models for studying vector-borne kinetoplastid infections","authors":"Laura Hauf , Markus Engstler","doi":"10.1016/j.mib.2025.102617","DOIUrl":"10.1016/j.mib.2025.102617","url":null,"abstract":"<div><div>Kinetoplastid infections, caused by <em>Leishmania</em> and <em>Trypanosoma</em> species, pose significant global health challenges, disproportionally affecting vulnerable populations in tropical regions. Despite the skin’s pivotal role as both an entry point and a reservoir for these parasites, the mechanistic understanding of host–parasite interactions at this interface remains limited.</div><div>Recent advancements in bioengineered skin models, such as full thickness skin equivalents and skin organoids, provide a promising complement to <em>in vivo</em> and <em>ex vivo</em> models. These <em>in vitro</em> systems address key challenges related to accessibility, reproducibility, and anatomical relevance, while potentially incorporating key tissue components, including immune cells and vascular structures. By replicating the complex structure of human skin at customizable levels of complexity, they offer powerful platforms for high-resolution studies of parasite–host interactions. Furthermore, by supporting natural vector transmission and enabling the simulation of diverse biological conditions, these systems open new avenues for investigating parasite development, tissue invasion, dissemination and immune dynamics.</div></div>","PeriodicalId":10921,"journal":{"name":"Current opinion in microbiology","volume":"86 ","pages":"Article 102617"},"PeriodicalIF":5.9,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144271741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cell cycle regulation in Escherichia coli: from governing principles, checkpoints, and control variables to molecular mechanisms","authors":"Alix Meunier, Sander K Govers","doi":"10.1016/j.mib.2025.102616","DOIUrl":"10.1016/j.mib.2025.102616","url":null,"abstract":"<div><div>All cells share the basic challenge of integrating the various processes that ensure their faithful replication. In most bacteria, this occurs without the dedicated regulatory machinery and additional layers of internal organization seen in eukaryotic cells. Despite this apparent reduction in complexity, bacterial replication is remarkably faithful and can be exceptionally fast. While spatiotemporal regulation of cell cycle processes is crucial for such efficient and reliable proliferation, many aspects of this currently remain elusive in bacteria. In this review, we focus on the cell cycle regulation of <em>Escherichia coli</em>, one of the best-studied bacterial models. We highlight how large-scale quantitative phenomenological studies have leveraged cellular variability to identify governing principles of cell cycle control in recent years. We discuss how these principles constrain the ongoing search for molecular mechanisms, examine the limitations of various approaches, and compare contradicting models and proposed molecular mechanisms.</div></div>","PeriodicalId":10921,"journal":{"name":"Current opinion in microbiology","volume":"86 ","pages":"Article 102616"},"PeriodicalIF":5.9,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144231899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Molly E Bunkofske , Fernando J Sanchez-Valdez , Rick L Tarleton
{"title":"The importance of persistence and dormancy in Trypanosoma cruzi infection and Chagas disease","authors":"Molly E Bunkofske , Fernando J Sanchez-Valdez , Rick L Tarleton","doi":"10.1016/j.mib.2025.102615","DOIUrl":"10.1016/j.mib.2025.102615","url":null,"abstract":"<div><div><em>Trypanosoma cruzi</em> typically establishes a life-long infection in its mammalian hosts, causing the destruction of muscle tissues and ultimately resulting in potentially fatal Chagas disease. In this review, we consider the array of avoidance mechanisms that allow for <em>T. cruzi</em> persistence, many of which are unconventional among protozoan pathogens but which collectively are highly effective in the face of otherwise potent host immune responses. We also reflect on the phenomenon of dormancy in <em>T. cruzi</em> amastigotes, which is likely not involved in the long-term persistence of infection. Lastly, we consider how these phenomena of persistence and dormancy complicate the effectiveness of potential therapeutic interventions to prevent Chagas disease.</div></div>","PeriodicalId":10921,"journal":{"name":"Current opinion in microbiology","volume":"86 ","pages":"Article 102615"},"PeriodicalIF":5.9,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144223495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}