Ana Belén Ramos-Aloi, Luciana Soledad Arias, Alipio Pinto, Jorge Goldstein
{"title":"Deleterious consequences of Shiga toxin in the CNS.","authors":"Ana Belén Ramos-Aloi, Luciana Soledad Arias, Alipio Pinto, Jorge Goldstein","doi":"10.1128/mmbr.00301-25","DOIUrl":"10.1128/mmbr.00301-25","url":null,"abstract":"<p><p>SUMMARYThe primary objective of this review is to provide an update on the most recent findings concerning the adverse effects of Shiga toxin-producing <i>Escherichia coli</i> (STEC) on the central nervous system (CNS), from both clinical and experimental perspectives. Considered the main predictor of death, STEC encephalopathy plays a critical role in hemolytic uremic syndrome (HUS), which affects between 11% and 64% of HUS patients and considerably increases the risk of morbidity and mortality. Of note, STEC encephalopathy in the absence of HUS has been observed in approximately 5% of cases. The ability of enterohemorrhagic <i>E. coli</i> to adapt to its microenvironment has been responsible for global outbreaks. Once in circulation, Shiga toxin rapidly induces endothelial damage via the Gb3 receptor. Brain inflammation in STEC encephalopathies has been consistently reported and experimentally confirmed. The entry of Shiga toxin into the brain leads to direct neuronal damage through its interaction with neuronal Gb3, as demonstrated in clinical case studies and experimental models. This review also discusses the adverse effects of STEC on the brain, which may arise from metabolic or circulatory disruptions, secondary damage to the CNS, or a multifactorial combination. Recent studies have highlighted the significance of neuroimaging techniques in diagnosing HUS encephalopathy. Efforts have been made to identify early neural biomarkers and develop corresponding treatments. Although various biomarkers have been reported, additional studies are needed for further development and standardization. Late-stage pharmacological treatments for encephalopathy are also discussed, both in clinical settings and experimental research.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0030125"},"PeriodicalIF":7.8,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13014766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145900787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Velvet regulators as master integrators of development, metabolism, and pathogenicity in filamentous fungi.","authors":"Wanping Chen, Ye-Eun Son, He-Jin Cho, Yonghua Wang, Hee-Soo Park, Jae-Hyuk Yu","doi":"10.1128/mmbr.00293-24","DOIUrl":"10.1128/mmbr.00293-24","url":null,"abstract":"<p><p>SUMMARYThe velvet family of fungal regulatory proteins constitutes a unique and evolutionarily conserved set of transcriptional and epigenetic regulators that coordinate development, secondary metabolism, and pathogenicity in filamentous fungi. Among them, VeA, VelB, VelC, and VosA form dynamic protein complexes that act as molecular hubs, integrating environmental cues such as light and nutrient availability with intrinsic developmental signals. Over the past two decades, extensive genetic, molecular, and biochemical studies-particularly in <i>Aspergillus</i> species-have elucidated the central roles of these regulators in governing asexual and sexual development, spore viability, cell wall integrity, and the biosynthesis of secondary metabolites. Recent advances in genome-wide analyses, proteomics, and chromatin mapping have expanded our understanding of how velvet complexes influence chromatin architecture and coordinate transcriptional programs across fungal genomes. Velvet proteins not only regulate gene clusters involved in specialized metabolism but also control developmental transitions and stress responses, including those related to virulence in plant and human fungal pathogens. The interaction between LaeA-a methyltransferase-and velvet proteins further links transcriptional regulation to epigenetic control. This review synthesizes recent findings on the molecular functions, regulatory networks, and evolutionary conservation of velvet regulators, highlighting their emerging significance as master integrators in fungal biology. We also discuss knowledge gaps and future directions, including the therapeutic and biotechnological potential of targeting velvet-mediated regulation.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0029324"},"PeriodicalIF":11.8,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13014761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147271266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The many journeys of botulinum neurotoxins and the bacteria that produce them-evolutionary, geographic, and research-related movements that have contributed to our understanding of a diverse pathogen.","authors":"Theresa J Smith","doi":"10.1128/mmbr.00230-25","DOIUrl":"10.1128/mmbr.00230-25","url":null,"abstract":"<p><p>SUMMARYBotulism is a neuroparalytic intoxication caused by a collection of large proteins, known as botulinum neurotoxins (BoNTs), that are related in amino acid sequence and structure. The extreme potency of BoNTs can be traced to their ability to access and enter cholinergic nerve terminals, their enzymatic nature, and their persistence within these cells. The extreme diversity seen among the BoNTs (7 serotypes and 44 subtypes) and the bacteria that produce them (7 species) stands in stark contrast to its close relative, tetanus toxin, which exists as a single protein entity produced by a single bacterial strain. Botulism may take many forms. It can be due to direct ingestion with BoNT (foodborne), or it may be the consequence of germination and toxin production within the body (infant and adult toxicoinfections, wound botulism). As BoNT-producing organisms are soil inhabitants, the cycle that results in botulism begins when the spores of these bacteria are moved to a location that is favorable for its growth and toxin production, be that in foods, humans, or animals. Multiple researchers in the United States did pioneering work concerning the etiology of botulism, including the identification of different types, the recognition of various host sensitivities, and the necessary conditions for germination and toxin production of these bacteria. As part of their work, several large collections of BoNT-producing bacteria were amassed. This review is a culmination of historical events relating to botulism in the United States and provides listings containing source information on strains from various collections that have provided valuable reference bacteria for basic research studies on botulism and the development of diagnostic tests, quality control testing, and botulism treatments and countermeasures, such as antisera and vaccines.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0023025"},"PeriodicalIF":11.8,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13014758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145912179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shinji Yamasaki, Atsushi Hinenoya, Dieter Bulach, M John Albert
{"title":"<i>Escherichia albertii</i>: the still unfolding journey of a misdiagnosed pathogen that became a new species and a new member of the family of attaching and effacing enteric bacterial pathogens.","authors":"Shinji Yamasaki, Atsushi Hinenoya, Dieter Bulach, M John Albert","doi":"10.1128/mmbr.00088-23","DOIUrl":"10.1128/mmbr.00088-23","url":null,"abstract":"<p><p>SUMMARY<i>Escherichia albertii,</i> initially identified as <i>Hafnia alvei</i>, by the commercial identification biochemical strip, API 20E, was isolated from an infant with diarrhea in Bangladesh in 1989. However, this bacterium was later renamed as a novel species, <i>E. albertii</i> (after M. John Albert, the discoverer) because of its similarities in biochemical and genetic properties to the genus <i>Escherichia</i>, but different from those of any known species in the genus. <i>E. albertii</i> possesses many pathogenic attributes, including a key one, which is the ability to produce attaching and effacing (A/E) lesions in the intestinal mucosa mediated by genes on a 35kb pathogenicity island called the locus of enterocyte effacement. Therefore, it is a member of the family of A/E pathogens. Some of the initially reported enteropathogenic <i>Escherichia coli</i> (EPEC), enterohemorrhagic <i>E. coli</i> (EHEC), <i>Shigella boydii</i> O13, and cytolethal distending toxin II-producing <i>E. coli</i> (CTEC-II) were later confirmed as <i>E. albertii. E. albertii</i> caused sporadic cases of diarrhea and diarrheal outbreaks and rarely extraintestinal infections. <i>E. albertii</i> was also associated with the death of birds in Scotland, UK, and Alaska in the USA. Not only birds (including chickens) but also mammals, including raccoons, seem to be major reservoirs of <i>E. albertii,</i> suggesting that <i>E. albertii</i> is an emerging zoonotic pathogen. Specific detection methods and selective and differential media for <i>E. albertii</i> have been developed for diagnosis. Several <i>E. albertii</i> isolates have been sequenced, revealing key characteristics of the organism. However, there are still many gaps in knowledge that exist regarding this bacterium. In this review, we will describe what is known about some key facets of this bacterium but also directions of future research to fill the knowledge gap.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0008823"},"PeriodicalIF":7.8,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13014760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145715025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Advancing Africa's bioeconomy and biosolutions through microbial natural product discovery: unlocking indigenous microbe potential for sustainability.","authors":"Adetomiwa Ayodele Adeniji, Du Toit Loots","doi":"10.1128/mmbr.00174-25","DOIUrl":"10.1128/mmbr.00174-25","url":null,"abstract":"<p><p>SUMMARYAfrica's rich microbial diversity presents a significant opportunity to drive innovation in healthcare, agriculture, and industrial biotechnology through microbial natural product discovery. However, despite its potential, the continent remains underrepresented in the global bioeconomy due to limited microbial culture repositories, inadequate genomic sequencing infrastructure, and weak commercialization models. This review highlights the critical role of microbial biotechnology in advancing Africa's bioeconomy and outlines a roadmap for leveraging indigenous microbial resources. By exploring the Bacterial and Viral Bioinformatics Resource Center (BV-BRC) database, we compiled the genomic distribution of traditional model and emerging non-model bacterial chassis indigenous to Africa. Although the survey is limited to BV-BRC data, this approach provides a reliable snapshot of microbial bioresources suitable for omics-driven biosolution development. The review integrates database insights with literature evidence to identify key microbial genera for further investigation. Key areas include microbial bioprospecting, functional omics, biofortification, and synthetic biology as drivers of sustainable innovation. Challenges such as scaling up biomanufacturing, bridging research-industry gaps, and establishing microbial biofoundries and biobanks are discussed as critical to strengthening Africa's biotechnology landscape. This paper also emphasizes the importance of enabling policy frameworks, strategic funding mechanisms, and public-private partnerships to accelerate commercialization pathways. By investing in microbial biotechnology, Africa can enhance food security, reduce dependency on chemical synthetic inputs, and address pressing issues such as antimicrobial resistance. Strengthening omics research capacity, expanding biomanufacturing infrastructure, and fostering cross-sector collaboration are essential steps toward unlocking Africa's untapped bioeconomic potential and positioning the continent as a global hub for sustainable biosolutions.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0017425"},"PeriodicalIF":7.8,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13014764/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145743281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abigail Kimball, Wanyi Huang, Iti Saraav, Lisa Funkhouser-Jones, Valentin Greigert, Fuxian Yang, Rui Xu, Yaoyu Feng, Lihua Xiao, L David Sibley
{"title":"New tools for exploring parasite biology and elucidating host-pathogen interactions in cryptosporidiosis.","authors":"Abigail Kimball, Wanyi Huang, Iti Saraav, Lisa Funkhouser-Jones, Valentin Greigert, Fuxian Yang, Rui Xu, Yaoyu Feng, Lihua Xiao, L David Sibley","doi":"10.1128/mmbr.00148-22","DOIUrl":"10.1128/mmbr.00148-22","url":null,"abstract":"<p><p>SUMMARYCryptosporidiosis is a major public health concern, the extent of which has only truly been appreciated within the last decade. <i>Cryptosporidium</i> research has undergone a renaissance, with new insights into population structure, species diversity, and evolution of the parasite driven by the advent of genetic transformation techniques and novel models for culture <i>in vitro</i> and <i>in vivo</i>. Here, we summarize the impact of these advances on our understanding of this important parasite. In the initial section, we focus on what we have learned about host range and infectivity from comparative genomics, briefly review the public health impact of human infection, and summarize recent findings on immune control and interactions with other gut microbes that influence infection. The second half of the review is devoted to new technical advances that have uncovered novel biological findings. As research on <i>Cryptosporidium</i> is still in its infancy, we finish by summarizing some of the challenges and opportunities for future research.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0014822"},"PeriodicalIF":11.8,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13014763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145912084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cell wall hydrolases of <i>Escherichia coli</i>.","authors":"Shambhavi Garde, Debnita Mongal, Manjula Reddy","doi":"10.1128/mmbr.00226-24","DOIUrl":"10.1128/mmbr.00226-24","url":null,"abstract":"<p><p>SUMMARYBacterial cell walls are made up of peptidoglycan (PG), a primary load-bearing layer that forms a protective exoskeleton around the cytoplasmic membrane. PG is a heteropolymer composed of glycan chains attached to short peptides that are crosslinked to each other, forming a mesh-like macromolecule that prevents osmotic lysis of the cell. Far from being a static exoskeleton, PG is a dynamic living polymer that undergoes continuous synthesis, expansion, remodeling, and turnover throughout the bacterial cell cycle. Central to the dynamic nature of PG is a finely tuned balance between two seemingly opposite processes-synthesis and hydrolysis. The PG synthases, which are essential for bacterial viability, have long been recognized as excellent drug targets and have therefore been studied extensively for decades. On the other hand, the significance of PG hydrolysis in diverse fundamental PG processes has become increasingly evident in recent years. Bacteria encode several highly conserved PG hydrolases with distinct substrate specificities that contribute to critical cellular processes, including cell wall expansion during growth, cell division, remodeling, and recycling, as well as predation and pathogenesis. Consequently, PG hydrolases represent promising targets for the development of novel antibacterial therapeutics. This review provides a comprehensive overview of the classification, physiological functions, and regulatory mechanisms governing the PG hydrolases in the model organism <i>Escherichia coli</i> and highlights parallels among related taxa across the bacterial kingdom.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0022624"},"PeriodicalIF":11.8,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13014775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145911796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhemin Zhang, Philip A Klenotic, Wei-Tse Hung, Rakesh Maharjan, Emma Kundracik, William D Gregor, Edward W Yu
{"title":"Do RND efflux pumps require protomeric cooperativity within the trimer to mediate antimicrobial resistance?","authors":"Zhemin Zhang, Philip A Klenotic, Wei-Tse Hung, Rakesh Maharjan, Emma Kundracik, William D Gregor, Edward W Yu","doi":"10.1128/mmbr.00304-25","DOIUrl":"10.1128/mmbr.00304-25","url":null,"abstract":"<p><p>SUMMARYGram-negative bacteria frequently use efflux pumps of the resistance-nodulation-cell division (RND) superfamily to extrude various toxic compounds out of the cell. In particular, the hydrophobe-amphiphile efflux 1 (HAE1) and heavy-metal efflux (HME)-RND families are critical for the export of antimicrobials and heavy metals, respectively. These efflux pumps assemble as trimers at the inner membrane of the bacterium. In this review, structural and functional data are summarized for several of these HAE1 and HME-RND efflux pumps from work performed in our laboratory and others. Experimental results and analyses suggest that individual protomers of these efflux pumps within their respective trimer function independently and in an uncoordinated manner to export substrates. Based on these observations, a molecular mechanism that governs substrate recognition and extrusion for these membrane proteins is proposed. It is our hope that researchers in the field will continue to build upon these efforts and employ various biophysical and biochemical methodologies to fully understand the mechanistic basis of important RND efflux systems.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0030425"},"PeriodicalIF":7.8,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13014756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145668883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Blondelle Matio Kemkuignou, Magnus Haahr, Matiss Maleckis, Ling Ding
{"title":"Discovery and biosynthesis of antifungal microbial secondary metabolites.","authors":"Blondelle Matio Kemkuignou, Magnus Haahr, Matiss Maleckis, Ling Ding","doi":"10.1128/mmbr.00075-25","DOIUrl":"10.1128/mmbr.00075-25","url":null,"abstract":"<p><p>SUMMARYThe high mortality associated with invasive fungal infections, coupled with limited therapeutic options, underscores the urgent need for antifungal agents with novel mechanisms of action. Natural products represent a particularly valuable resource, providing structurally diverse and evolutionary refined scaffolds that often outperform those found in synthetic libraries. Historically, microorganisms have proven to be a rich source of antibiotics and other therapeutic agents. Access to diverse phylogenetic lineages and biosynthetic pathways has been essential for antifungal drug development. In this review, we highlight the chemical and biosynthetic diversity of antifungal natural products derived from both fungi and bacteria. We emphasize that microbial natural products continue to play a crucial role in antifungal development, particularly through the integration of natural product chemistry, microbiology, genetics, and advanced omics technologies.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0007525"},"PeriodicalIF":11.8,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13014777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145959554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effects of cooling on <i>E. coli</i>'s DNA organization, structure, and gene expression.","authors":"Amir M Arsh, Miguel M Azevedo, Andre S Ribeiro","doi":"10.1128/mmbr.00153-25","DOIUrl":"10.1128/mmbr.00153-25","url":null,"abstract":"<p><p>SUMMARYBacteria are frequently subject to potentially lethal temperature shifts in their natural environments. We review the changes in the structure and dynamics of the gene regulatory network of the bacterium <i>Escherichia coli</i> during cold shocks. First, we describe the effects of cold shocks on higher-order cellular structures (cytoplasm and membrane) and functions (growth, division, and biofilm formation). Next, we focus on the nucleoid, DNA supercoiling, topoisomerases, ATP, and nucleoid-associated proteins. Afterward, we describe the mutual effects of changes in transcription dynamics and DNA supercoiling during cold shocks, followed by the consequent genome-wide, time-lapse changes in the transcriptome. Finally, we briefly describe the post-transcriptional effects of cold shocks and the cellular processes of acclimatization. In the end, we discuss how studying this topic can assist in developing temperature-sensitive synthetic genetic circuits, efficient bioindustrial processes, and new means to cope with bacterial antibiotic tolerance.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0015325"},"PeriodicalIF":7.8,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12713389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145452377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}