{"title":"Structural analysis of resistance-nodulation cell division transporters.","authors":"Philip A Klenotic, Edward W Yu","doi":"10.1128/mmbr.00198-23","DOIUrl":"10.1128/mmbr.00198-23","url":null,"abstract":"<p><p>SUMMARYInfectious bacteria have both intrinsic and acquired mechanisms to combat harmful biocides that enter the cell. Through adaptive pressures, many of these pathogens have become resistant to many, if not all, of the current antibiotics used today to treat these often deadly infections. One prominent mechanism is the upregulation of efflux systems, especially the resistance-nodulation-cell division class of exporters. These tripartite systems consist of an inner membrane transporter coupled with a periplasmic adaptor protein and an outer membrane channel to efficiently transport a diverse array of substrates from inside the cell to the extracellular space. Detailed mechanistic insight into how these inner membrane transporters recognize and shuttle their substrates can ultimately inform both new antibiotic and efflux pump inhibitor design. This review examines the structural basis of substrate recognition of these pumps and the molecular mechanisms underlying multidrug extrusion, which in turn mediate antimicrobial resistance in bacterial pathogens.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":null,"pages":null},"PeriodicalIF":8.0,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11332337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140318669","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}
Mario Pedraza-Reyes, Karen Abundiz-Yañez, Alejandra Rangel-Mendoza, Lissett E Martínez, Rocío C Barajas-Ornelas, Mayra Cuéllar-Cruz, Hilda C Leyva-Sánchez, Víctor M Ayala-García, Luz I Valenzuela-García, Eduardo A Robleto
{"title":"<i>Bacillus subtilis</i> stress-associated mutagenesis and developmental DNA repair.","authors":"Mario Pedraza-Reyes, Karen Abundiz-Yañez, Alejandra Rangel-Mendoza, Lissett E Martínez, Rocío C Barajas-Ornelas, Mayra Cuéllar-Cruz, Hilda C Leyva-Sánchez, Víctor M Ayala-García, Luz I Valenzuela-García, Eduardo A Robleto","doi":"10.1128/mmbr.00158-23","DOIUrl":"10.1128/mmbr.00158-23","url":null,"abstract":"<p><p><b>SUMMARY</b>The metabolic conditions that prevail during bacterial growth have evolved with the faithful operation of repair systems that recognize and eliminate DNA lesions caused by intracellular and exogenous agents. This idea is supported by the low rate of spontaneous mutations (10<sup>-9</sup>) that occur in replicating cells, maintaining genome integrity. In contrast, when growth and/or replication cease, bacteria frequently process DNA lesions in an error-prone manner. DNA repairs provide cells with the tools needed for maintaining homeostasis during stressful conditions and depend on the developmental context in which repair events occur. Thus, different physiological scenarios can be anticipated. In nutritionally stressed bacteria, different components of the base excision repair pathway may process damaged DNA in an error-prone approach, promoting genetic variability. Interestingly, suppressing the mismatch repair machinery and activating specific DNA glycosylases promote stationary-phase mutations. Current evidence also suggests that in resting cells, coupling repair processes to actively transcribed genes may promote multiple genetic transactions that are advantageous for stressed cells. DNA repair during sporulation is of interest as a model to understand how transcriptional processes influence the formation of mutations in conditions where replication is halted. Current reports indicate that transcriptional coupling repair-dependent and -independent processes operate in differentiating cells to process spontaneous and induced DNA damage and that error-prone synthesis of DNA is involved in these events. These and other noncanonical ways of DNA repair that contribute to mutagenesis, survival, and evolution are reviewed in this manuscript.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":null,"pages":null},"PeriodicalIF":8.0,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11332352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140318668","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}
Amy L Enright, William J Heelan, Ryan D Ward, Jason M Peters
{"title":"CRISPRi functional genomics in bacteria and its application to medical and industrial research.","authors":"Amy L Enright, William J Heelan, Ryan D Ward, Jason M Peters","doi":"10.1128/mmbr.00170-22","DOIUrl":"10.1128/mmbr.00170-22","url":null,"abstract":"<p><p>SUMMARYFunctional genomics is the use of systematic gene perturbation approaches to determine the contributions of genes under conditions of interest. Although functional genomic strategies have been used in bacteria for decades, recent studies have taken advantage of CRISPR (clustered regularly interspaced short palindromic repeats) technologies, such as CRISPRi (CRISPR interference), that are capable of precisely modulating expression of all genes in the genome. Here, we discuss and review the use of CRISPRi and related technologies for bacterial functional genomics. We discuss the strengths and weaknesses of CRISPRi as well as design considerations for CRISPRi genetic screens. We also review examples of how CRISPRi screens have defined relevant genetic targets for medical and industrial applications. Finally, we outline a few of the many possible directions that could be pursued using CRISPR-based functional genomics in bacteria. Our view is that the most exciting screens and discoveries are yet to come.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":null,"pages":null},"PeriodicalIF":8.0,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11332340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141162305","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}
Sangeetha Senthil Kumar, Michael D L Johnson, Justin E Wilson
{"title":"Insights into the enigma of oral streptococci in carcinogenesis.","authors":"Sangeetha Senthil Kumar, Michael D L Johnson, Justin E Wilson","doi":"10.1128/mmbr.00095-23","DOIUrl":"10.1128/mmbr.00095-23","url":null,"abstract":"<p><p>SUMMARYThe genus <i>Streptococcus</i> consists of a taxonomically diverse group of Gram-positive bacteria that have earned significant scientific interest due to their physiological and pathogenic characteristics. Within the genus <i>Streptococcus,</i> viridans group streptococci (VGS) play a significant role in the oral ecosystem, constituting approximately 80% of the oral biofilm. Their primary role as pioneering colonizers in the oral cavity with multifaceted interactions like adherence, metabolic signaling, and quorum sensing contributes significantly to the complex dynamics of the oral biofilm, thus shaping oral health and disease outcomes. Perturbations in oral streptococci composition drive oral dysbiosis and therefore impact host-pathogen interactions, resulting in oral inflammation and representing VGS as an opportunistic pathogen. The association of oral streptococci in tumors across distant organs, spanning the esophagus, stomach, pancreas, and colon, illuminates a potential association between oral streptococci, inflammation, and tumorigenesis. This finding emphasizes the need for further investigations into the role of oral streptococci in mucosal homeostasis and their involvement in carcinogenesis. Hence, here, we review the significance of oral streptococci in biofilm dynamics and how the perturbation may impact mucosal immunopathogenesis in the context of cancer, with a vision of exploiting oral streptococci for cancer intervention and for the development of non-invasive cancer diagnosis.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":null,"pages":null},"PeriodicalIF":8.0,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11338076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140175536","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}
Myrto Katsipoulaki, Mark H T Stappers, Dhara Malavia-Jones, Sascha Brunke, Bernhard Hube, Neil A R Gow
{"title":"<i>Candida albicans</i> and <i>Candida glabrata</i>: global priority pathogens.","authors":"Myrto Katsipoulaki, Mark H T Stappers, Dhara Malavia-Jones, Sascha Brunke, Bernhard Hube, Neil A R Gow","doi":"10.1128/mmbr.00021-23","DOIUrl":"10.1128/mmbr.00021-23","url":null,"abstract":"<p><p>SUMMARYA significant increase in the incidence of <i>Candida</i>-mediated infections has been observed in the last decade, mainly due to rising numbers of susceptible individuals. Recently, the World Health Organization published its first fungal pathogen priority list, with <i>Candida</i> species listed in medium, high, and critical priority categories. This review is a synthesis of information and recent advances in our understanding of two of these species<i>-Candida albicans</i> and <i>Candida glabrata</i>. Of these, <i>C. albicans</i> is the most common cause of candidemia around the world and is categorized as a critical priority pathogen. <i>C. glabrata</i> is considered a high-priority pathogen and has become an increasingly important cause of candidemia in recent years. It is now the second most common causative agent of candidemia in many geographical regions. Despite their differences and phylogenetic divergence, they are successful as pathogens and commensals of humans. Both species can cause a broad variety of infections, ranging from superficial to potentially lethal systemic infections. While they share similarities in certain infection strategies, including tissue adhesion and invasion, they differ significantly in key aspects of their biology, interaction with immune cells, host damage strategies, and metabolic adaptations. Here we provide insights on key aspects of their biology, epidemiology, commensal and pathogenic lifestyles, interactions with the immune system, and antifungal resistance.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":null,"pages":null},"PeriodicalIF":8.0,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11332356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141237758","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":"White-opaque switching in <i>Candida albicans</i>: cell biology, regulation, and function.","authors":"David R Soll","doi":"10.1128/mmbr.00043-22","DOIUrl":"10.1128/mmbr.00043-22","url":null,"abstract":"<p><p>SUMMARY<i>Candida albicans</i> remains a major fungal pathogen colonizing humans and opportunistically invading tissue when conditions are predisposing. Part of the success of <i>C. albicans</i> was attributed to its capacity to form hyphae that facilitate tissue invasion. However, in 1987, a second developmental program was discovered, the \"white-opaque transition,\" a high-frequency reversible switching system that impacted most aspects of the physiology, cell architecture, virulence, and gene expression of <i>C. albicans</i>. For the 15 years following the discovery of white-opaque switching, its role in the biology of <i>C. albicans</i> remained elusive. Then in 2002, it was discovered that in order to mate, <i>C. albicans</i> had to switch from white to opaque, a unique step in a yeast mating program. In 2006, three laboratories simultaneously identified a putative master switch gene, which led to a major quest to elucidate the underlying mechanisms that regulate white-opaque switching. Here, the evolving discoveries related to this complicated phenotypic transition are reviewed in a quasi-chronological order not only to provide a historical perspective but also to highlight several unique characteristics of white-opaque switching, which are fascinating and may be important to the life history and virulence of this persistent pathogen. Many of these characteristics have not been fully investigated, in many cases, leaving intriguing questions unresolved. Some of these include the function of unique channeled pimples on the opaque cell wall, the capacity to form opaque cells in the absence of the master switch gene <i>WOR1</i>, the formation of separate \"pathogenic\" and \"sexual\" biofilms, and the possibility that a significant portion of natural strains colonizing the lower gastrointestinal tract may be in the opaque phase. This review addresses many of these characteristics with the intent of engendering interest in resolving questions that remain unanswered.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":null,"pages":null},"PeriodicalIF":8.0,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11332339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140306182","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":"IS<i>26</i> and the IS<i>26</i> family: versatile resistance gene movers and genome reorganizers.","authors":"Christopher J Harmer, Ruth M Hall","doi":"10.1128/mmbr.00119-22","DOIUrl":"10.1128/mmbr.00119-22","url":null,"abstract":"<p><p><b>SUMMARY</b>In Gram-negative bacteria, the insertion sequence IS<i>26</i> is highly active in disseminating antibiotic resistance genes. IS<i>26</i> can recruit a gene or group of genes into the mobile gene pool and support their continued dissemination to new locations by creating pseudo-compound transposons (PCTs) that can be further mobilized by the insertion sequence (IS). IS<i>26</i> can also enhance expression of adjacent potential resistance genes. IS<i>26</i> encodes a DDE transposase but has unique properties. It forms cointegrates between two separate DNA molecules using two mechanisms. The well-known copy-in (replicative) route generates an additional IS copy and duplicates the target site. The recently discovered and more efficient and targeted conservative mechanism requires an IS in both participating molecules and does not generate any new sequence. The unit of movement for PCTs, known as a translocatable unit or TU, includes only one IS<i>26</i>. TU formed by homologous recombination between the bounding IS<i>26</i>s can be reincorporated via either cointegration route. However, the targeted conservative reaction is key to generation of arrays of overlapping PCTs seen in resistant pathogens. Using the copy-in route, IS<i>26</i> can also act on a site in the same DNA molecule, either inverting adjacent DNA or generating an adjacent deletion plus a circular molecule carrying the DNA segment lost and an IS copy. If reincorporated, these circular molecules create a new PCT. IS<i>26</i> is the best characterized IS in the IS<i>26</i> family, which includes IS<i>257</i>/IS<i>431</i>, ISSau10, IS<i>1216</i>, IS<i>1006</i>, and IS<i>1008</i> that are also implicated in spreading resistance genes in Gram-positive and Gram-negative pathogens.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":null,"pages":null},"PeriodicalIF":8.0,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11332343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140022193","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}
Victoria E Sepúlveda, William E Goldman, Daniel R Matute
{"title":"Genotypic diversity, virulence, and molecular genetic tools in <i>Histoplasma</i>.","authors":"Victoria E Sepúlveda, William E Goldman, Daniel R Matute","doi":"10.1128/mmbr.00076-23","DOIUrl":"10.1128/mmbr.00076-23","url":null,"abstract":"<p><p><b>SUMMARY</b>Histoplasmosis is arguably the most common fungal respiratory infection worldwide, with hundreds of thousands of new infections occurring annually in the United States alone. The infection can progress in the lung or disseminate to visceral organs and can be difficult to treat with antifungal drugs. <i>Histoplasma</i>, the causative agent of the disease, is a pathogenic fungus that causes life-threatening lung infections and is globally distributed. The fungus has the ability to germinate from conidia into either hyphal (mold) or yeast form, depending on the environmental temperature. This transition also regulates virulence. <i>Histoplasma</i> and histoplasmosis have been classified as being of emergent importance, and in 2022, the World Health Organization included <i>Histoplasma</i> as 1 of the 19 most concerning human fungal pathogens. In this review, we synthesize the current understanding of the ecological niche, evolutionary history, and virulence strategies of <i>Histoplasma</i>. We also describe general patterns of the symptomatology and epidemiology of histoplasmosis. We underscore areas where research is sorely needed and highlight research avenues that have been productive.</p>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":null,"pages":null},"PeriodicalIF":8.0,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11332355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141179978","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":"Lipoic acid attachment to proteins: stimulating new developments","authors":"John E. Cronan","doi":"10.1128/mmbr.00005-24","DOIUrl":"https://doi.org/10.1128/mmbr.00005-24","url":null,"abstract":"SUMMARYLipoic acid-modified proteins are essential for central metabolism and pathogenesis.\u0000In recent years, the Escherichia coli and Bacillus subtilis lipoyl assembly pathways have been modified and extended to archaea and diverse eukaryotes\u0000including ...","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":null,"pages":null},"PeriodicalIF":12.9,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140615386","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}
Ousmane H. CisséLiang MaJoseph A. Kovacs1Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA, Joseph Heitman
{"title":"Retracing the evolution of Pneumocystis species, with a focus on the human pathogen Pneumocystis jirovecii","authors":"Ousmane H. CisséLiang MaJoseph A. Kovacs1Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA, Joseph Heitman","doi":"10.1128/mmbr.00202-22","DOIUrl":"https://doi.org/10.1128/mmbr.00202-22","url":null,"abstract":"Microbiology and Molecular Biology Reviews, Ahead of Print. <br/>","PeriodicalId":18520,"journal":{"name":"Microbiology and Molecular Biology Reviews","volume":null,"pages":null},"PeriodicalIF":12.9,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140587950","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}