Microbiology And Molecular Biology Reviews[JOURNAL]
Sun
200 papers
Structure, assembly, and mechanism of the MmpL family of transporters.
Zhang Z, Kundracik E, Li W … +10 more , Babii S, Choukate K, Aboagye A, Klenotic PA, Maharjan R, Gregor WD, Swarts BM, Zgurskaya HI, Jackson M, Yu EW
Microbiol Mol Biol Rev · 2026 Jun · PMID 42370679 · Publisher ↗
SUMMARYThe mycobacterial cell envelope, one of the most complex membranes found in bacteria, plays a major role in bacterial pathogenesis, virulence, and antimicrobial resistance. Biogenesis and modeling of this cell env...
SUMMARYThe mycobacterial cell envelope, one of the most complex membranes found in bacteria, plays a major role in bacterial pathogenesis, virulence, and antimicrobial resistance. Biogenesis and modeling of this cell envelope are heavily influenced by the mycobacterial membrane protein large (MmpL) family of transporters due to their ability to export fatty acids and lipid components. Select MmpL transporters can also function as siderophore exporters to help regulate the acquisition of iron, which is critical for mycobacterial survival. Additionally, certain MmpLs can participate in active efflux of antimycobacterial drugs, directly contributing to antimicrobial resistance. Given the physiological significance of these MmpL membrane proteins and their potential to serve as important antimycobacterial targets, questions regarding their functional roles, cellular assemblies, interactions, and regulation need to be fully addressed. In this review, we summarize our current knowledge on the structures and functions of these MmpL transporters. It is our hope that researchers in the field will continue to build upon these efforts and apply various structural, biophysical, and biochemical methodologies to fully elucidate how MmpL transporters coordinate to participate in cell envelope biogenesis, cell elongation and division, and antimicrobial resistance.
Killer meiotic drivers in fungi.
Hua Y
Microbiol Mol Biol Rev · 2026 Jun · PMID 42370678 · Publisher ↗
SUMMARYMendel's Law of Segregation posits an equal probability for each allele to be inherited during sexual reproduction. This process, however, is subverted by killer meiotic drivers (KMDs)-selfish genetic elements tha...
SUMMARYMendel's Law of Segregation posits an equal probability for each allele to be inherited during sexual reproduction. This process, however, is subverted by killer meiotic drivers (KMDs)-selfish genetic elements that enhance their own transmission in driver+/driver- heterozygotes by selectively eliminating meiotic products lacking the driver allele. Such elements arise recurrently during evolution, and the genomic conflicts they generate are considered potent evolutionary forces shaping genome architecture and sexual reproductive systems. While documented across diverse eukaryotes-including plants, fungi, and animals-most KMDs remain molecularly uncharacterized, and their actual prevalence in nature remains elusive. In fungi, KMDs can act at two distinct life-cycle stages: by directly killing sexual spores (fungal gametes)-hence termed "spore killers"-or by targeting haploid progeny after spore germination. Fungal models have profoundly advanced our understanding of these elements. This review synthesizes current knowledge on characterized fungal KMDs (from , , , and ), emphasizing their molecular basis and interplay with the host. Approaches for KMD discovery are also discussed. Growing evidence from fungi suggests that these selfish elements are likely far more prevalent than previously appreciated.
From dividing to dormant: embracing the full activity spectrum for environmental microorganisms.
Guigard L, Bal V, Bintarti AF … +6 more , Buron M, Chavan E, Gonzalo M, Liu X, Zheng W, Shade A
Microbiol Mol Biol Rev · 2026 Jun · PMID 42345569 · Publisher ↗
SUMMARYMicroorganisms can cope with stress by entering dormancy, a viable state of reduced metabolic activity that enables persistence, dispersal, and long-term survival. However, microbial life in environmental systems...
SUMMARYMicroorganisms can cope with stress by entering dormancy, a viable state of reduced metabolic activity that enables persistence, dispersal, and long-term survival. However, microbial life in environmental systems is best understood as a spectrum of metabolic activity, spanning from highly active, dividing cells to deeply dormant phenotypes. This spectrum reflects dynamic survival strategies under fluctuating conditions, with critical implications for ecosystem stability, gene dissemination, and resilience to disturbances in natural and human-influenced systems. Yet, microbial activity is often treated as binary (active vs. dormant), oversimplifying a biological continuity that remains technically difficult to quantify. Here, we synthesize advances in microbial dormancy to reconceptualize activity as a spectrum. We review current and emerging methods to quantify environmental activity, linking each to the Central Dogma of molecular biology (DNA to RNA to protein) to guide interpretation along a generalizable continuum. Through a literature synthesis of terrestrial, aquatic, and wastewater treatment ecosystems, we compare how methods estimate active cells and populations. We recommend standardized reporting of total community size, active cell abundance, and proportional activity to enrich the interpretation of microbiome 'omics data, with activity intensity and active-inactive switching providing deeper insights. To achieve this, we advocate for increased accessibility and throughput of precise activity-discriminating technologies, alongside renewed use of reliable methods like direct cell counts and activity stains. Adopting this spectrum-based perspective will improve our ability to tackle key societal challenges, such as understanding microbial contributions to ecosystem function under climate change and gene dispersal at human-environment interfaces.
Role of TMDs in Class I viral fusion proteins.
Ortiz-Mateu J, Martinez-Gil L
Microbiol Mol Biol Rev · 2026 Jun · PMID 42328981 · Publisher ↗
SUMMARYClass I fusion proteins are trimeric viral membrane proteins that mediate fusion between the virion and cellular membranes. In their prefusion state, they comprise three domains: a globular "head" domain that bind...
SUMMARYClass I fusion proteins are trimeric viral membrane proteins that mediate fusion between the virion and cellular membranes. In their prefusion state, they comprise three domains: a globular "head" domain that binds the target cell receptor, a helical "stalk" domain, and a transmembrane domain (TMD) at the carboxy-terminal end that anchors the protein in the viral membrane. However, it is now evident that the role of the TMD extends beyond simple membrane anchoring. This review explores the dynamic and regulatory functions of the TMD throughout the viral life cycle. TMDs contribute to intracellular trafficking and modulate membrane fusion activity and receptor binding. During virion assembly, they facilitate the incorporation of fusion proteins into budding particles, and influence virion formation and release. Furthermore, TMDs mediate interactions between viral and host proteins, shaping the structural organization of viral complexes, and impacting cellular responses to infection. Collectively, these findings highlight the TMD as a critical determinant of viral fitness and infectivity, underscoring its potential as a novel therapeutic target.
The microbiome in reptile health, disease, and ecology.
Hoffbeck C, Taylor MW
Microbiol Mol Biol Rev · 2026 Jun · PMID 42307225 · Publisher ↗
SUMMARYReptiles are a diverse and speciose class of animals that are broadly threatened by habitat loss, climate change, and other factors. From a microbiological perspective, reptiles have historically been examined as...
SUMMARYReptiles are a diverse and speciose class of animals that are broadly threatened by habitat loss, climate change, and other factors. From a microbiological perspective, reptiles have historically been examined as a source of disease, particularly salmonellosis, with most studies being culture-based investigations into causative agents of disease and potential for zoonoses. More recent work has sought to characterize the oral, skin, and gut microbiomes of reptiles more broadly to understand their contribution to reptile health and digestion. Non-avian reptiles are particularly interesting as ectothermic tetrapods, which usually lay eggs and have limited interaction with their young, as their digestion and life history strategies diverge substantially from the more well-studied mammals. Here, we review the reptile skin, oral, gut, eggshell, and nest microbiomes, along with the relationship between the microbiome and temperature stress. We present findings that distinguish the reptile microbiome from those of other studied vertebrate taxa, and place them in the context of their phylogenetic and ecological similarities to other animals. We discuss major disease-causing agents in reptiles, which was historically the main lens through which to view reptile microbiology, along with potential zoonoses. Finally, we examine how temperature and thermoregulation interact with the microbiome in reptiles, and how the microbiome may play a role in reptile conservation.
Overcoming the energy-dependent barrier to aminoglycoside uptake: multimodal strategies to sensitize persisters.
Baek S, Choe YJ, Yune PS … +2 more , Mylonakis E, Kim W
Microbiol Mol Biol Rev · 2026 Jun · PMID 42300731 · Publisher ↗
SUMMARYPersistent infections pose a major therapeutic challenge due to the formation of metabolically dormant persister cells that survive antibiotic exposure without acquiring genetic resistance. Despite their potent b...
SUMMARYPersistent infections pose a major therapeutic challenge due to the formation of metabolically dormant persister cells that survive antibiotic exposure without acquiring genetic resistance. Despite their potent bactericidal activity, aminoglycosides fail against these persisters due to their reliance on energy-dependent uptake driven by the proton motive force (PMF). This review synthesizes emerging strategies designed to overcome this critical bottleneck. Metabolic stimulation using specific carbon sources or PMF-modulating agents reactivates membrane energetics, thereby restoring aminoglycoside uptake in dormant cells. Membrane-targeting adjuvants bypass PMF altogether, enabling antibiotic entry via biophysical remodeling and disruption of the lipid bilayer. Additionally, we discuss rationally engineered aminoglycoside hybrids, such as peptide-conjugated variants, that achieve self-directed, energy-independent penetration while preserving ribosomal targeting. Collectively, these approaches highlight that aminoglycoside failure against persisters can be a modifiable physiological limitation rather than an issue of intrinsic resistance. The convergence of metabolic and membrane-based potentiation underscores the therapeutic potential of combinatorial regimens tailored to the unique bioenergetic state of persisters. Their clinical translation, combined with efforts to address toxicity, may transform the treatment landscape of recalcitrant infections and mitigate the risk of relapse.
NrdR-a unique nucleotide-sensing regulator of prokaryotic ribonucleotide reductases.
Rozman Grinberg I, Lundin D, Cohen G … +4 more , Borovok I, Aharonowitz Y, Sjöberg B-M, Logan DT
Microbiol Mol Biol Rev · 2026 Jun · PMID 42267808 · Publisher ↗
SUMMARYThe transcriptional regulator NrdR is present in most bacteria and in some archaea, but is lacking in eukaryotes. It controls the expression of operons of the universal and essential ribonucleotide reductase (RNR)...
SUMMARYThe transcriptional regulator NrdR is present in most bacteria and in some archaea, but is lacking in eukaryotes. It controls the expression of operons of the universal and essential ribonucleotide reductase (RNR) enzymes, which provide building blocks of DNA by reducing ribonucleotides to their corresponding deoxyribonucleotides. The NrdR protein consists of an N-terminal zinc-ribbon domain that can bind to specific NrdR boxes in DNA, followed by an ATP-cone domain that binds adenosine nucleotides. Discovered 20 years ago, it was not until the recent high-resolution structures of NrdR in its DNA-bound and -unbound forms that its intricate mechanism of action could be described in detail. Contrary to early assumptions, the ATP-cone in NrdR has two nucleotide-binding sites, an inner and an outer site. When cellular dATP is low, NrdR is loaded with ATP in both sites and forms oligomers unable to bind to DNA, allowing transcription of RNR-encoding operons, and DNA replication and repair. When dATP levels increase, ATP in the outer site is substituted for dATP, NrdR will bind to DNA, and the expression of RNR-encoding genes will be inhibited. Interestingly, many RNRs also carry an ATP-cone that binds either one or two adenosine nucleotides, and that acts as an allosteric on/off switch of its enzyme activity. On the basis of current knowledge, this is a unique utilization of the same horizontally transferable domain for controlling both enzyme expression and enzyme activity.
Effective influenza treatment: a comprehensive review of challenges and advances.
Pomeshikova K, Poromov A, Schmidtke M … +1 more , Makarov V
Microbiol Mol Biol Rev · 2026 Jun · PMID 42262144 · Publisher ↗
SUMMARYInfluenza viruses remain a serious global health problem, causing annual epidemics and potential pandemics with significant morbidity and mortality. Antiviral therapy, particularly with direct-acting antivirals (D...
SUMMARYInfluenza viruses remain a serious global health problem, causing annual epidemics and potential pandemics with significant morbidity and mortality. Antiviral therapy, particularly with direct-acting antivirals (DAAs), is a critical component of influenza control. This comprehensive review analyzes the current landscape of DAA drugs, with special attention paid to the complexity of synthesis, pharmacokinetic properties, and the development of antiviral resistance. We evaluated approved treatments, including neuraminidase (NA) inhibitors, viral RNA polymerase inhibitors, hemagglutinin (HA) inhibitors, and M2 ion channel blockers. We identify several critical obstacles to effective treatment: (i) the high genetic variability of influenza viruses, which facilitates the emergence of resistance, particularly in the case of M2 blockers (widespread) and, to a lesser but concerning extent, NA and polymerase inhibitors, both through natural evolution and selective pressure during drug treatment, and (ii) the suboptimal pharmacokinetic profiles of many existing drugs. This review provides a crucial framework for evaluating existing and investigational drugs for influenza, emphasizing the need to develop balanced therapeutic strategies that consider efficacy, resistance management, and global accessibility. The novelty of this review is a comprehensive comparative analysis of not only the drugs officially recommended by the WHO but also a wide range of other anti-influenza drugs approved in individual countries or under development. We have identified key comparative aspects that are discussed in detail here and are not always brought together in other reviews. The purpose of the article is to provide a generalized overview of the current state of knowledge, identify key trends and problems, and discuss future prospects without providing new primary data or experimental results.
Toward synthetic biology in mushroom-forming Agaricomycete fungi: from tools to applications.
Allen PM, Sinar D, Schwartz S … +1 more , Hill-Maini V
Microbiol Mol Biol Rev · 2026 Jun · PMID 42233661 · Full text
SUMMARYMushroom-forming Agaricomycete fungi underpin global nutrient cycling and carbon sequestration, and support large and growing markets across food, medicinal supplements, and biomaterials. Yet most commercial and r...
SUMMARYMushroom-forming Agaricomycete fungi underpin global nutrient cycling and carbon sequestration, and support large and growing markets across food, medicinal supplements, and biomaterials. Yet most commercial and research uses still rely on wild-type strains, highlighting the opportunity for genetic engineering to expand possibilities for both fundamental research and biotechnological applications. In this review, we highlight progress toward synthetic biology in Agaricomycetes, and outline the main barriers that limit predictable genetic engineering. We emphasize engineering constraints unique to mushroom biology, including complex sexual cycles, heterokaryosis, and strain instability during transformation and outgrowth. We then transition to gene expression bottlenecks: the scarcity of characterized promoters and terminators, the challenges for gene integration posed by the condensed nature of Agaricomycete genomes, and the effects of introns and specific sequence motifs. Finally, drawing inspiration from progress in related fungi and other eukaryotes, we highlight the priorities for the field: systematic cross-species evaluation of genetic parts, development of more sophisticated gene-editing strategies, higher-throughput screening methods, and the establishment of a unifying model system. These advances would enable new possibilities in the study and use of Agaricomycetes, establishing these elusive organisms as programmable platforms for sustainable biomanufacturing, designer biomaterials, climate solutions, and mechanistic studies of fungal biology.
and : their past, present, and future in scientific research and publications.
Bernstein HD, Detweiler CS, Freddolino L … +4 more , Karp P, Lovett ST, Slauch JM, Torres AG
Microbiol Mol Biol Rev · 2026 Jun · PMID 42227755 · Full text
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Moonlighting in metabolism: bifunctional enzymes control nitrogen metabolism in .
Gibhardt J, Lieber MM, Götz CS … +6 more , Völker F, Blank LM, Forchhammer K, Jayaraman V, Noda-Garcia L, Commichau FM
Microbiol Mol Biol Rev · 2026 Jun · PMID 42126227 · Full text
SUMMARYGlutamate is an essential building block and the most important amino group donor in the cell. The reactions involved in synthesis and degradation link carbon to nitrogen metabolism. The synthesis and activity of...
SUMMARYGlutamate is an essential building block and the most important amino group donor in the cell. The reactions involved in synthesis and degradation link carbon to nitrogen metabolism. The synthesis and activity of the enzymes catalyzing these reactions must, therefore, be precisely regulated. In the Gram-positive model bacterium , glutamate is exclusively synthesized by the combined action of the glutamine synthetase (GS) and the glutamate synthase (GOGAT). The GS catalyzes the ATP-dependent assimilation of ammonium, resulting in the formation of glutamine. Glutamine is converted together with 2-oxoglutarate by the GOGAT into glutamate, which can be used either for further assimilation of ammonium, or as a building block, or amino group donor. The glutamate dehydrogenases (GDHs) GudB and RocG are strictly devoted to glutamate degradation. In recent years, exciting new observations have been made in nitrogen metabolism in . The GS, GOGAT, and the GDHs are multifunctional enzymes, with the GS and GDHs acting as trigger enzymes in the control of gene expression, in addition to their enzymatic activity. The glutamate-synthesizing GOGAT acts as a counter enzyme, inactivating the major GDH GudB to prevent a futile cycle. In this review, we intend to summarize the current state of knowledge about nitrogen metabolism in and discuss open questions that need to be answered in the future.
Roles of transcription factors and chromatin remodelers in regulating innate immune responses in .
Warushavithana PS, Howard DT, West JD … +1 more , Lažetić V
Microbiol Mol Biol Rev · 2026 Jun · PMID 42126198 · Full text
SUMMARYEffective immunity requires the ability to mount strong pathogen defenses while minimizing detrimental effects on organismal fitness. To achieve this balance, many immune genes are maintained in a transcriptionall...
SUMMARYEffective immunity requires the ability to mount strong pathogen defenses while minimizing detrimental effects on organismal fitness. To achieve this balance, many immune genes are maintained in a transcriptionally repressed but responsive state, ensuring rapid induction upon infection and timely repression once the threat subsides. This dynamic regulation is controlled by transcription factors and chromatin remodelers that fine-tune the accessibility of immune loci. The nematode provides a powerful model for dissecting these mechanisms in non-professional immune cells. Its antiviral RNA interference (RNAi) pathway serves as a rapid, sequence-specific silencing system targeting viral RNA. Complementing RNAi, the intracellular pathogen response represents a specialized, inducible transcriptional program that protects from intracellular pathogens, including viruses and microsporidia. In addition, pathways regulated by STAT family transcription factors coordinate immune activation in a pathogen- and tissue-specific manner, providing further regulatory diversity. This review explores how transcriptional and chromatin mechanisms coordinate these distinct immune programs to maintain effective yet balanced immune responses. Investigating these pathways in continues to uncover both conserved and novel principles of immune regulation, offering insight into how organisms integrate transcriptional control with physiological constraints to thrive in a pathogen-rich environment.
Turning defects into defenses: the potential and challenges of defective viral genome-based antiviral strategies.
Li D, Lin M-H, Hao H … +3 more , Zhou P, Maniam P, Harrich D
Microbiol Mol Biol Rev · 2026 Jun · PMID 42089568 · Full text
SUMMARYViral defective interfering particles (DIPs) are produced during replication by many RNA viruses, acting as non-infectious particles containing defective viral genomes (DVGs). DVGs are most clearly defined and mec...
SUMMARYViral defective interfering particles (DIPs) are produced during replication by many RNA viruses, acting as non-infectious particles containing defective viral genomes (DVGs). DVGs are most clearly defined and mechanistically understood in positive- and negative-strand RNA viruses, and this review focuses on these RNA viruses in which DVGs and DIPs are best characterized. DVGs function as molecular parasites that rely on co-infection with a standard virus to obtain essential viral proteins needed for their replication. This parasitic relationship interferes with wild-type virus replication, making DIPs attractive antiviral candidates because they resist viral escape through mutation. Beyond replication interference, DVGs have emerged as potent stimulators of innate immunity, capable of inhibiting diverse, unrelated viruses by triggering robust antiviral responses. These dual mechanisms, direct interference and immune activation, highlight the value of DIPs/DVGs as a versatile antiviral strategy. Advances in understanding DIP/DVG formation, immune modulation, and therapeutic engineering underscore their promise for broad-spectrum antiviral applications. This review explores recent breakthroughs and addresses the critical remaining challenges for DIPs/DVGs to progress from promising preclinical agents to effective clinical antivirals.
(p)ppGpp: the magic goes on.
Potrykus K, Bryszkowska K, Gąsior F … +1 more , Klasa W
Microbiol Mol Biol Rev · 2026 Jun · PMID 42053290 · Full text
SUMMARYBacteria are constantly exposed to changing environmental conditions, and to survive they need to adapt quickly, adjusting their gene expression and metabolism to make the most of the resources available. One of t...
SUMMARYBacteria are constantly exposed to changing environmental conditions, and to survive they need to adapt quickly, adjusting their gene expression and metabolism to make the most of the resources available. One of the mechanisms involved is the stringent response, characterized by production of specific guanosine derivatives-ppGpp and pppGpp (collectively called (p)ppGpp). These regulators exert their action and coordinate a global response at many different levels, for example, transcription, translation, nucleotide metabolism, DNA replication, and carbon and lipid metabolism. In this review, we discuss how (p)ppGpp is synthesized and degraded, how it controls different cellular processes and their interplay with other second messengers. A description of differences in (p)ppGpp regulation in Gram-negative and Gram-positive bacteria, along with recent findings and some historical perspectives, is provided. We argue that although much is known about the stringent response and the novel discoveries are definitely advancing the (p)ppGpp field, they are not exhaustive. Instead, they seem to constantly point to aspects that are still waiting to be uncovered-thus, the (p)ppGpp magic goes on.
Updated scheme for the classification of bacteriocins in gram-positive bacteria and a comprehensive overview for Lactobacillaceae.
Dillen J, Maeyens LT, Hill C … +1 more , Lebeer S
Microbiol Mol Biol Rev · 2026 Jun · PMID 42053281 · Full text
SUMMARYMany gram-positive bacteria, particularly those within the family Lactobacillaceae, possess significant biotechnological potential across food, feed, supplement, pharmaceutical, and agricultural sectors. Numerous...
SUMMARYMany gram-positive bacteria, particularly those within the family Lactobacillaceae, possess significant biotechnological potential across food, feed, supplement, pharmaceutical, and agricultural sectors. Numerous species produce bacteriocins or ribosomally synthesized antimicrobial peptides, some of which undergo post-translational modifications that may confer a competitive advantage in complex microbial communities. These beneficial properties, along with their capacity to produce such bioactive molecules, make Lactobacillaceae a valuable microbial group with broad application potential. This review provides a comprehensive overview of bacteriocin classes within Lactobacillaceae, detailing their classification, mechanisms of action, and genetic organization. We propose a unified classification system, including an extension of existing classes and a standardized, source-based nomenclature for ribosomally produced and post-translationally modified peptides (RiPPs) and unmodified bacteriocins from gram-positive bacteria to enhance clarity and consistency. While proposed for Lactobacillaceae, our proposal fits within the broader scope of the field for the development of community standards in line with the scope of, for example, the "Minimum Information about a Biosynthetic Gene cluster" (MIBiG) database. We also systematically reviewed all reported bacteriocins within Lactobacillaceae, identifying 474 individual bacteriocins to date. Despite advances in genome and peptidome technologies, most remain only partially characterized. Notably, the majority of producing strains originate from food-related niches, highlighting the untapped potential of species from underexplored environments. Given the growing threat of antibiotic resistance and the demand for natural food preservatives, there is an urgent need to fully characterize these bioactive molecules and discover new ones from lesser-studied Lactobacillaceae species for future applications.
Looking beyond the rumen: uncovering opportunities to improve health and performance by considering the whole gastrointestinal tract.
Costello MK, McClure JC, Olson EG … +3 more , Tarcin HA, Mantovani HC, Ricke SC
Microbiol Mol Biol Rev · 2026 Jun · PMID 42053280 · Full text
SUMMARYModulating the lower gastrointestinal tract (GIT) is an untapped opportunity for improvement in cattle production. The microbial communities across the GIT regions are closely related to host function and anatomic...
SUMMARYModulating the lower gastrointestinal tract (GIT) is an untapped opportunity for improvement in cattle production. The microbial communities across the GIT regions are closely related to host function and anatomical structures, impacting digestion and feed efficiency, the immune response, growth, and methane production. In this review, the characteristics of each GIT location are discussed to better understand how different anatomical structures of the host digestive tract and the microbial communities interact within and between GIT locations. There are several major issues faced by the cattle industry that are impacted by the lower GIT (duodenum, jejunum, ileum, cecum, and large intestines), including managing the inflammatory response, release of waste products, and food safety concerns. As there continues to be a push for agricultural sustainability, improved food safety, reduced economic losses, and efficient early life development, exploring the less understood contributions of the lower GIT is crucial. Finally, this review will explore increasingly convenient and affordable sampling and sequencing techniques that will transform our understanding of the bovine GIT.
Typhoid toxin: reframing enteric fever.
Galán JE
Microbiol Mol Biol Rev · 2026 Jun · PMID 42041253 · Full text
SUMMARY serovars Typhi and Paratyphi A cause enteric (typhoid/paratyphoid) fever, a systemic disease that remains a major source of morbidity and mortality worldwide. The most distinctive clinical manifestations, such as...
SUMMARY serovars Typhi and Paratyphi A cause enteric (typhoid/paratyphoid) fever, a systemic disease that remains a major source of morbidity and mortality worldwide. The most distinctive clinical manifestations, such as sustained fever with relative bradycardia, leukopenia, neuropsychiatric symptoms/encephalopathy, and ileal perforation, have long lacked a unifying mechanistic explanation. Over the past two decades, studies of typhoid toxin have reframed how we understand this disease. Typhoid toxin is a human-adapted, chimeric AB exotoxin assembled exclusively inside infected cells. It couples an ADP-ribosyltransferase (PltA) and a DNase I-like nuclease (CdtB) on a pentameric delivery ring (PltB or the alternate, PltC), that recognizes N-acetylneuraminic acid (Neu5Ac)-terminated human sialoglycans. The toxin is produced by bacteria residing within the -containing vacuole (SCV), secreted across the bacterial envelope into the SCV lumen by a phage-derived pathway now classified as type 10 secretion system, sorted for export by the host CI-M6PR/COPII trafficking machinery, and then re-enters distant target cells via retrograde transport to the endoplasmic reticulum (ER). Recent work has linked typhoid toxin to leukopenia, blood-brain barrier disruption causing encephalopathy, gut-vascular and immune dysfunction leading to intestinal perforation, and hepatobiliary injury. The discovery of an alternate B-subunit (PltC) established a paradigm of modular B-subunit exchange that diversifies receptor usage, tissue tropism, and biology. Collectively, these insights redefine typhoid fever as a toxin-driven immunovascular disease and identify actionable targets for neutralizing antibodies and barrier-protective therapies.
A 60-year journey with a fungal transporter: from classical genetics to functional, structural, and evolutionary insights.
Diallinas G, Scazzocchio C
Microbiol Mol Biol Rev · 2026 Jun · PMID 42041252 · Full text
SUMMARYTransporters are transmembrane proteins that mediate the selective translocation of metabolites, ions, and drugs across biological membranes. Their activity is essential for cellular communication, nutrition, deto...
SUMMARYTransporters are transmembrane proteins that mediate the selective translocation of metabolites, ions, and drugs across biological membranes. Their activity is essential for cellular communication, nutrition, detoxification, homeostasis, and responses to stress. Despite their fundamental biological and biomedical importance, particularly their involvement in genetic diseases and multidrug resistance in microbes and cancer cells, transporters remained relatively understudied until recently. This was largely due to the technical challenges of isolating and functionally characterizing these dynamic proteins, whose structure, function, and cellular expression continuously depends on specific interactions with membrane lipids. Nevertheless, since the mid-1960s, several transporters have been identified and extensively characterized at the genetic and physiological levels in model microorganisms, including fungi. In this review, we trace the 60-year research journey of UapA, a uric acid-xanthine transporter from the filamentous fungus (Ascomycota). The UapA story spans from early classical genetic analyses to the recent determination of its high-resolution structure. We describe the development of genetic, molecular, and cellular tools and how these enabled the functional dissection of UapA and were subsequently used for other transporters, including studies on cellular expression and turnover regulation. We additionally highlight up-to-date structural approaches that refined our knowledge on the transport mechanism, how substrate specificity is determined, and on membrane trafficking pathways underlying biogenesis and endocytosis of UapA and other transporters. The concepts developed through 60 years of persistent work on UapA have established important paradigms relevant to fungal physiology that have proven to be broadly applicable to understanding transporter-linked processes in other eukaryotic organisms.
Genetic factors contributing to viral myocarditis.
Wang Z, Mohamud Y, Luo H
Microbiol Mol Biol Rev · 2026 Jun · PMID 42007711 · Full text
SUMMARYViral myocarditis is an inflammatory disease of the heart muscle caused by diverse viral pathogens and shaped by complex interactions between viruses and host responses, ultimately leading to myocardial inflammati...
SUMMARYViral myocarditis is an inflammatory disease of the heart muscle caused by diverse viral pathogens and shaped by complex interactions between viruses and host responses, ultimately leading to myocardial inflammation and dysfunction. While environmental factors contribute to disease onset, growing evidence highlights a central role for host genetic determinants in influencing susceptibility, severity, and clinical outcomes. In addition, sex-specific differences have emerged as important modifiers of immune responses and disease progression. This review examines the genetic architecture of viral myocarditis, integrating human genetic studies with mechanistic insights derived largely from coxsackievirus B3 (CVB3) models, which provide the most comprehensive experimental framework for dissecting gene-disease relationships . By integrating genetic associations with their functional implications, we aim to deepen the understanding of viral myocarditis and inform future research directions and potential therapeutic strategies.
Catching our breath: development of interventions and therapies for respiratory syncytial virus.
Mathew AM, Neilsen G, Lan S … +9 more , Shooter SL, Zheng JSJ, Estes J, Cao D, Schinazi RF, Singh US, Liang B, Lee S, Sarafianos SG
Microbiol Mol Biol Rev · 2026 Jun · PMID 42007710 · Full text
SUMMARYRespiratory syncytial virus (RSV) continues to be a significant global health concern, particularly affecting infants, young children, and older adults. Although the virus was discovered decades ago, a complete cu...
SUMMARYRespiratory syncytial virus (RSV) continues to be a significant global health concern, particularly affecting infants, young children, and older adults. Although the virus was discovered decades ago, a complete cure remains elusive. RSV is a leading cause of lower respiratory tract infections, contributing to significant illness and mortality around the world. Recent scientific advances have brought promising developments in the fight against RSV. Progress in vaccine technology has led to the approval and distribution of preventative vaccines, particularly for high-risk groups. Monoclonal antibodies, designed to target and neutralize the virus, are used both to prevent and treat infections. Antiviral treatments, though still limited, are also showing potential in reducing disease severity and duration. Advanced animal and controlled human infection models have bolstered preclinical and clinical research, allowing for the testing and refinement of therapeutic candidates in more physiologically relevant systems. These models are playing a crucial role in understanding disease mechanisms and evaluating the efficacy of new interventions. As the field rapidly evolves, it is essential to pause and assess our current standing in the fight against RSV. In many ways, we are finally -equipped with better tools and a deeper understanding, yet still facing the challenges of a persistent and complex virus. Continued innovation, investment, and global collaboration will be essential to translate these developments into widespread therapy for those most vulnerable to RSV.
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