{"title":"Ribosome roadblocks and traffic controllers in bacteria.","authors":"Mahmoud Shoman, Mee-Ngan Frances Yap","doi":"10.1128/mmbr.00346-25","DOIUrl":"10.1128/mmbr.00346-25","url":null,"abstract":"<p><p>Protein synthesis by ribosomes proceeds through the sequential stages of initiation, elongation, termination, and ribosome recycling. In most bacteria, coupled transcription-translation enhances the efficiency of transcription but limits opportunities to repair or eliminate faulty mRNAs, thereby increasing the likelihood that ribosomes encounter incomplete or damaged transcripts. Furthermore, mRNA integrity can be compromised by transcriptional errors, abortive transcription, nucleolytic cleavage, or chemical damage. Translation of such defective transcripts, as well as other hard-to-translate mRNAs, can impede elongation or termination, resulting in stalled ribosome complexes that sequester ribosomes and tRNAs, thereby reducing their availability for subsequent rounds of translation. To maintain translation capacity, bacteria employ dedicated ribosome rescue and quality control pathways that resolve stalled complexes and promote the turnover of aberrant mRNAs and nascent polypeptides. Here, we summarize the molecular mechanisms underlying bacterial ribosome stalling, describe the pathways that rescue stalled ribosomes, and discuss current technologies for detecting ribosome stalling. We also highlight the physiological roles of programmed ribosome stalling and explore the potential of ribosome rescue pathways as druggable sites.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0034625"},"PeriodicalIF":11.8,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149183153","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":"Fidelity during bacterial protein synthesis.","authors":"Cierra Wilson, Zhihui Lyu, Jiqiang Ling","doi":"10.1128/mmbr.00337-25","DOIUrl":"https://doi.org/10.1128/mmbr.00337-25","url":null,"abstract":"<p><p>SUMMARYTranslational fidelity is maintained throughout evolution and ensures the accurate flow of genetic information from mRNA to protein. Both aminoacyl-tRNA synthetases and ribosomes use substrate selection and proofreading to lower translational errors. However, genetic mutations and environmental changes frequently alter translational fidelity. Recent technological advances have enabled sensitive detection of translational errors and high-throughput screening of conditions that alter translational fidelity. With a focus on <i>Escherichia coli</i> and <i>Salmonella enterica</i>, this article reviews the methods used to quantitate translational errors <i>in vivo</i>, the impact of various stresses and metabolic changes on translational fidelity, and the effects of altered translational fidelity on evolution, stress adaptation, and bacteria-host interactions.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0033725"},"PeriodicalIF":11.8,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170549","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":"Toward broad-spectrum coronavirus vaccines: navigating viral evolution from past epidemics to future resilience.","authors":"Muzhuo Wang, Weijie Wang, Zhikai Chen, Lu Lu, Zezhong Liu, Shibo Jiang","doi":"10.1128/mmbr.00100-25","DOIUrl":"https://doi.org/10.1128/mmbr.00100-25","url":null,"abstract":"<p><p><b>SUMMARY</b>Newly emerged highly pathogenic coronavirus species, including SARS-CoV, MERS-CoV, and SARS-CoV-2, have successively triggered outbreaks worldwide over the past 25 years. Recently, several MERS-related coronaviruses have been identified from bats or pangolins. These viruses, along with previously found SARS-related coronaviruses, pose significant potential to infect humans and trigger pandemics. Therefore, it is necessary to develop broad-spectrum vaccines that can combat both currently circulating coronaviruses and those that may emerge in the future. Currently, approved COVID-19 vaccines provide strong protection against pre-Omicron variants, while their effectiveness against post-Omicron variants is reduced, and cross-protection against other potential coronaviruses remains limited. In the present review, we discuss vaccine research on SARS-CoV and MERS-CoV prior to the COVID-19 outbreak, as well as vaccine development following the outbreak. We also focus on strategies for developing broad-spectrum coronavirus vaccines and provide a perspective on future directions for coronavirus vaccine development.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0010025"},"PeriodicalIF":11.8,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111863","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":"Efficient host transmission of measles virus: disentangling misconceptions from established findings.","authors":"Angela Liu, Patrick L Sinn","doi":"10.1128/mmbr.00221-25","DOIUrl":"https://doi.org/10.1128/mmbr.00221-25","url":null,"abstract":"<p><p><b>SUMMARY</b>Measles virus (MeV) is considered the most contagious human virus. This review critically examines explanations for MeV's extraordinary transmissibility. Although substantial progress has been made in understanding MeV infection, pathogenesis, and host spread, the fundamental question of why MeV is markedly more transmissible than other structurally similar respiratory viruses within the same taxonomic families remains unresolved. Many commonly cited explanations are either incorrect, oversimplified, or insufficiently supported by rigorous experimental evidence. Notably, there is a striking lack of studies that directly investigate the mechanisms governing MeV transmission. This knowledge gap persists in part because humans are the only natural reservoir for MeV, and thus the most relevant experimental models can be costly, technically challenging, and limited in ability. Moreover, studies addressing MeV environmental stability have relied largely on <i>in vitro</i> laboratory conditions that may have limited relevance to real-world transmission scenarios. While these studies have yielded useful observations, they often lack definitive mechanistic insight into efficient host-to-host spread. In this review, we discuss multiple strategies to investigate and define the efficient transmission of MeV, including (i) epidemiology, (ii) stability in controlled environments, (iii) infectious dose, (iv) incubation period, and (v) shedding from the respiratory epithelium. As will be discussed, quantitative, head-to-head comparisons of MeV transmission dynamics with those of other common respiratory viruses, such as influenza virus, rhinovirus, and respiratory syncytial virus, are notably absent. A clearer understanding of the mechanisms that govern efficient MeV transmission may inform strategies to reduce spread in educational, healthcare, and community settings.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0022125"},"PeriodicalIF":11.8,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111837","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}
Anastasia Chasapi, Alexandros Michailidis, Lynn M Schriml, Claudio Donati, Nikos C Kyrpides, Christos A Ouzounis
{"title":"The grammar of the pangenome: terms, concepts, methods, and emerging patterns-a general framework for comparative genomics and genome biology.","authors":"Anastasia Chasapi, Alexandros Michailidis, Lynn M Schriml, Claudio Donati, Nikos C Kyrpides, Christos A Ouzounis","doi":"10.1128/mmbr.00403-25","DOIUrl":"https://doi.org/10.1128/mmbr.00403-25","url":null,"abstract":"<p><p>SUMMARYThe concept of the pangenome has emerged as the approach of choice for targeted comparative genomics across groups of organisms, from strain or population levels within a species to broader taxonomic or phenotypic categories. Pangenome analyses employ diverse procedures that inevitably introduce reproducibility challenges. Nevertheless, they have already yielded important insights into the structure, function, and evolution of archaeal, bacterial, and eukaryotic genomes across space, time, biogeography, and phylogeny. There is a wide range of applications from vaccine design to synthetic biology that are expected to yield additional technological and biomedical tools for genome biology and biotechnology. We review here the basic concepts underpinning pangenome research, including the estimation of gene and protein family numbers, the modeling of open and closed pangenomes, and key definitions relevant to reporting guidelines. We list and compare computational platforms, algorithms, and data structures, along with their salient features. We present key findings from 249 taxa covering 17,858 genome sequences, subjected to such analyses, and discuss major patterns observed, such as novel families per genome and pangenome size estimates for this validated data set. We propose revised criteria for pangenomes, standard operating procedures, and further targets to enhance the reproducibility of analysis and expand opportunities for experimental and computational comparative genomics. This framework attempts to clarify current methodologies and chart a path forward for integrating pangenome analyses.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0040325"},"PeriodicalIF":11.8,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111869","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":"Beyond the parasite: skin-intrinsic cytolytic circuits drive disease in cutaneous leishmaniasis and reveal targets for host-directed therapy.","authors":"Fernanda O Novais, Phillip Scott","doi":"10.1128/mmbr.00058-25","DOIUrl":"10.1128/mmbr.00058-25","url":null,"abstract":"<p><p><b>SUMMARY</b>Cutaneous leishmaniasis (CL) is a globally prevalent parasitic disease in which tissue pathology often arises primarily from immune-mediated damage rather than uncontrolled parasite replication. Despite effective Th1 responses and the production of IFN-γ, lesions often fail to resolve, highlighting an uncoupling of protective immunity from disease pathogenesis. This review synthesizes evidence from experimental models and human studies demonstrating that skin-intrinsic cytolytic inflammatory circuits-rather than parasite burden-are dominant drivers of lesion persistence and treatment failure in CL. Central to this pathway is the accumulation of cytotoxic CD8<sup>+</sup> T cells within lesions, where perforin-dependent cell death triggers NLRP3 inflammasome activation and IL-1β production. IL-1β acts as a potent amplifier of inflammation by promoting neutrophil recruitment, tissue injury, and local hypoxia, which further programs pathogenic CD8<sup>+</sup> T-cell differentiation. These responses are exacerbated by alterations of the skin microbiome, particularly the dominance of <i>Staphylococcus aureus</i>, and are normally constrained by Foxp3<sup>+</sup> regulatory T cells that limit excessive IFN-γ-driven cytotoxicity. In parallel, parasite persistence within permissive macrophage subsets provides a continuous antigenic stimulus that sustains inflammation without achieving sterilizing immunity. Together, these interconnected pathways form a self-reinforcing inflammatory circuit that promotes ulceration, chronic disease, and therapeutic failure. Importantly, this pathogenic network is largely dispensable for parasite control and, therefore, provides multiple targets for host-directed therapies that could complement anti-parasitic drugs and improve clinical outcomes in CL.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0005825"},"PeriodicalIF":11.8,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149069889","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":"Translation factors that keep the ribosome Pro-active.","authors":"Heather A Feaga","doi":"10.1128/mmbr.00017-26","DOIUrl":"10.1128/mmbr.00017-26","url":null,"abstract":"<p><p>SUMMARYRibosomes produce the staggering array of proteins that perform the structural and enzymatic feats of the cell. Therefore, most of the cell's energy goes toward producing ribosomes and the work performed by them. The work of the ribosome is relatively simple-decode mRNA codons and catalyze the formation of peptide bonds. By marching iteratively along the length of an open reading frame, a complete peptide is produced. Ribosomes catalyze the formation of peptide bonds at a rate of approximately 15 amino acids per second. However, bonds between amino acids do not form with equal efficiency, and ribosomes can become stalled at difficult-to-translate sequences. Proline is unique among the amino acids in that its side chain is covalently bonded to the peptide backbone to form a rigid ring. The rigidity of proline, and especially tracts of proline, makes it a difficult substrate for peptide bond formation, but it is also an essential motif in many protein structures. Elongation factor P (EF-P) is the star player for facilitating translation of polyproline tracts. However, recently identified factors play an important supporting role, and loss of these factors incurs a severe fitness defect in the absence of EF-P. These factors include an EF-P paralog, EfpL, as well as the ABCF ATPase YfmR/Uup and YebC2. The abundance and partial redundancy of factors that prevent ribosome stalling at polyprolines highlights the structural importance of polyproline tracts and the need to facilitate their translation. Here, we review recently identified translation factors that prevent ribosome stalling at polyprolines in bacteria.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0001726"},"PeriodicalIF":11.8,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13602936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679125","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":"LPS in gram-negative bacterial growth and physiology: outside but fully integrated.","authors":"Ryan A Valdez, Petra Anne Levin","doi":"10.1128/mmbr.00394-25","DOIUrl":"10.1128/mmbr.00394-25","url":null,"abstract":"<p><p>SUMMARYFor single-celled organisms, the cell envelope is the thin barrier between life and death, responding dynamically to both the ever-expanding self and the ever-changing environment. Failure to balance these responses can lead to disastrous consequences, such as lysis. In gram-negative bacteria, the cell envelope is tripartite, consisting of two lipid bilayers with the periplasm, an aqueous space containing the thin peptidoglycan sacculus, between them. The outer of these lipid bilayers-aptly called the outer membrane-is asymmetric, bearing phospholipids on the inner leaflet and lipopolysaccharide (LPS) on the outer leaflet. Surface-exposed, highly immunoreactive, and essential to nearly all tested gram-negative bacteria, the overall architecture of LPS is largely conserved, but its modifications are subject to a myriad of variations. LPS has been studied extensively for its roles in pathogenesis and immunobiology and as a target of potential novel antibiotics. However, LPS exists in both free-living and pathogenic bacteria, suggesting it plays a critical role in bacterial physiology independent of the host. This aspect of LPS biology and its contribution to overall gram-negative cell physiology remains an area of active investigation. Addressing this gap, here we describe recent work detailing the essential contributions of LPS to bacterial physiology: particularly its role in cell envelope rigidity, its contributions to outer membrane capacity and fluidity, and the mechanisms integrating LPS synthesis into diverse aspects of cell envelope biogenesis during growth and division. We end with a discussion of the subset of gram-negative organisms that survive-either naturally or through genetic manipulation-in the absence of LPS and the adaptations that make this possible.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0039425"},"PeriodicalIF":11.8,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13540297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148701627","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}
Siobhan A Cusack, Sebastián Riquelme-Barrios, Luis Rivera-Montero, Leonardo Vásquez-Camus, Dania Devassy, Kirsten Jung
{"title":"Compendium of RNA modifications for bacterial stress adaptation.","authors":"Siobhan A Cusack, Sebastián Riquelme-Barrios, Luis Rivera-Montero, Leonardo Vásquez-Camus, Dania Devassy, Kirsten Jung","doi":"10.1128/mmbr.00374-25","DOIUrl":"10.1128/mmbr.00374-25","url":null,"abstract":"<p><p>SUMMARYRNA modifications in the tRNA, rRNA, and mRNA constitute a widespread layer of post-transcriptional gene regulation, commonly known as the epitranscriptome. In bacteria, tRNA and rRNA modifications are well documented and play essential roles in tRNA folding, rRNA maturation, translation, and peptidyl transfer. Although mRNA modifications have been extensively characterized in eukaryotes, their functional implications for mRNA fate in prokaryotes remain uncertain, and their identities and locations are the subject of an emerging field of research. Importantly, RNA modification is a dynamic process, and variation in the presence and abundance of these modifications has significant consequences for bacterial physiology. Here, we discuss current knowledge of modified RNA nucleotides in bacteria, with a particular focus on their roles in bacterial adaptation to environmental stress.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0037425"},"PeriodicalIF":11.8,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13602947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148604926","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, Emma Kundracik, Wei Li, Svitlana Babii, Komal Choukate, Alex Aboagye, Philip A Klenotic, Rakesh Maharjan, William D Gregor, Benjamin M Swarts, Helen I Zgurskaya, Mary Jackson, Edward W Yu
{"title":"Structure, assembly, and mechanism of the MmpL family of transporters.","authors":"Zhemin Zhang, Emma Kundracik, Wei Li, Svitlana Babii, Komal Choukate, Alex Aboagye, Philip A Klenotic, Rakesh Maharjan, William D Gregor, Benjamin M Swarts, Helen I Zgurskaya, Mary Jackson, Edward W Yu","doi":"10.1128/mmbr.00139-26","DOIUrl":"10.1128/mmbr.00139-26","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":" ","pages":"e0013926"},"PeriodicalIF":11.8,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13602945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148345823","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}