Microbiology And Molecular Biology Reviews[JOURNAL]
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200 papers
Mechanical Forces Govern Interactions of Host Cells with Intracellular Bacterial Pathogens.
Bastounis EE, Radhakrishnan P, Prinz CK … +1 more , Theriot JA
Microbiol Mol Biol Rev · 2022 Jun · PMID 35285720 · Full text
To combat infectious diseases, it is important to understand how host cells interact with bacterial pathogens. Signals conveyed from pathogen to host, and vice versa, may be either chemical or mechanical. While the molec...
To combat infectious diseases, it is important to understand how host cells interact with bacterial pathogens. Signals conveyed from pathogen to host, and vice versa, may be either chemical or mechanical. While the molecular and biochemical basis of host-pathogen interactions has been extensively explored, relatively less is known about mechanical signals and responses in the context of those interactions. Nevertheless, a wide variety of bacterial pathogens appear to have developed mechanisms to alter the cellular biomechanics of their hosts in order to promote their survival and dissemination, and in turn many host responses to infection rely on mechanical alterations in host cells and tissues to limit the spread of infection. In this review, we present recent findings on how mechanical forces generated by host cells can promote or obstruct the dissemination of intracellular bacterial pathogens. In addition, we discuss how extracellular mechanical signals influence interactions between host cells and intracellular bacterial pathogens. Examples of such signals include shear stresses caused by fluid flow over the surface of cells and variable stiffness of the extracellular matrix on which cells are anchored. We highlight bioengineering-inspired tools and techniques that can be used to measure host cell mechanics during infection. These allow for the interrogation of how mechanical signals can modulate infection alongside biochemical signals. We hope that this review will inspire the microbiology community to embrace those tools in future studies so that host cell biomechanics can be more readily explored in the context of infection studies.
Mating-Type Switching in Budding Yeasts, from Flip/Flop Inversion to Cassette Mechanisms.
Wolfe KH, Butler G
Microbiol Mol Biol Rev · 2022 Jun · PMID 35195440 · Full text
Mating-type switching is a natural but unusual genetic control process that regulates cell identity in ascomycete yeasts. It involves physically replacing one small piece of genomic DNA by another, resulting in replaceme...
Mating-type switching is a natural but unusual genetic control process that regulates cell identity in ascomycete yeasts. It involves physically replacing one small piece of genomic DNA by another, resulting in replacement of the master regulatory genes in the mating pathway and hence a switch of cell type and mating behavior. In this review, we concentrate on recent progress that has been made on understanding the origins and evolution of mating-type switching systems in budding yeasts (subphylum Saccharomycotina). Because of the unusual nature and the complexity of the mechanism in Saccharomyces cerevisiae, mating-type switching was assumed until recently to have originated only once or twice during yeast evolution. However, comparative genomics analysis now shows that switching mechanisms arose many times independently-at least 11 times in budding yeasts and once in fission yeasts-a dramatic example of convergent evolution. Most of these lineages switch mating types by a flip/flop mechanism that inverts a section of a chromosome and is simpler than the well-characterized 3-locus cassette mechanism (//) used by S. cerevisiae. Mating-type switching (secondary homothallism) is one of the two possible mechanisms by which a yeast species can become self-fertile. The other mechanism (primary homothallism) has also emerged independently in multiple evolutionary lineages of budding yeasts, indicating that homothallism has been favored strongly by natural selection. Recent work shows that HO endonuclease, which makes the double-strand DNA break that initiates switching at the S. cerevisiae locus, evolved from an unusual mobile genetic element that originally targeted a glycolytic gene, .
Chemotropism and Cell-Cell Fusion in Fungi.
Clark-Cotton MR, Jacobs KC, Lew DJ
Microbiol Mol Biol Rev · 2022 Mar · PMID 35138122 · Full text
Fungi exhibit an enormous variety of morphologies, including yeast colonies, hyphal mycelia, and elaborate fruiting bodies. This diversity arises through a combination of polar growth, cell division, and cell fusion. Bec...
Fungi exhibit an enormous variety of morphologies, including yeast colonies, hyphal mycelia, and elaborate fruiting bodies. This diversity arises through a combination of polar growth, cell division, and cell fusion. Because fungal cells are nonmotile and surrounded by a protective cell wall that is essential for cell integrity, potential fusion partners must grow toward each other until they touch and then degrade the intervening cell walls without impacting cell integrity. Here, we review recent progress on understanding how fungi overcome these challenges. Extracellular chemoattractants, including small peptide pheromones, mediate communication between potential fusion partners, promoting the local activation of core cell polarity regulators to orient polar growth and cell wall degradation. However, in crowded environments, pheromone gradients can be complex and potentially confusing, raising the question of how cells can effectively find their partners. Recent findings suggest that the cell polarity circuit exhibits searching behavior that can respond to pheromone cues through a remarkably flexible and effective strategy called exploratory polarization.
The Facts and Family Secrets of Plasmids That Replicate via the Rolling-Circle Mechanism.
Garcillán-Barcia MP, Pluta R, Lorenzo-Díaz F … +2 more , Bravo A, Espinosa M
Microbiol Mol Biol Rev · 2022 Mar · PMID 34878299 · Full text
Plasmids are self-replicative DNA elements that are transferred between bacteria. Plasmids encode not only antibiotic resistance genes but also adaptive genes that allow their hosts to colonize new niches. Plasmid transf...
Plasmids are self-replicative DNA elements that are transferred between bacteria. Plasmids encode not only antibiotic resistance genes but also adaptive genes that allow their hosts to colonize new niches. Plasmid transfer is achieved by conjugation (or mobilization), phage-mediated transduction, and natural transformation. Thousands of plasmids use the rolling-circle mechanism for their propagation (RCR plasmids). They are ubiquitous, have a high copy number, exhibit a broad host range, and often can be mobilized among bacterial species. Based upon the replicon, RCR plasmids have been grouped into several families, the best known of them being pC194 and pUB110 (Rep_1 family), pMV158 and pE194 (Rep_2 family), and pT181 and pC221 (Rep_trans family). Genetic traits of RCR plasmids are analyzed concerning (i) replication mediated by a DNA-relaxing initiator protein and its interactions with the cognate DNA origin, (ii) lagging-strand origins of replication, (iii) antibiotic resistance genes, (iv) mobilization functions, (v) replication control, performed by proteins and/or antisense RNAs, and (vi) the participating host-encoded functions. The mobilization functions include a relaxase initiator of transfer (Mob), an origin of transfer, and one or two small auxiliary proteins. There is a family of relaxases, the MOB family represented by plasmid pMV158, which has been revisited and updated. Family secrets, like a putative open reading frame of unknown function, are reported. We conclude that basic research on RCR plasmids is of importance, and our perspectives contemplate the concept of One Earth because we should incorporate bacteria into our daily life by diminishing their virulence and, at the same time, respecting their genetic diversity.
Evolutionary Morphogenesis of Sexual Fruiting Bodies in Basidiomycota: Toward a New Evo-Devo Synthesis.
Virágh M, Merényi Z, Csernetics Á … +5 more , Földi C, Sahu N, Liu XB, Hibbett DS, Nagy LG
Microbiol Mol Biol Rev · 2022 Mar · PMID 34817241 · Full text
The development of sexual fruiting bodies is one of the most complex morphogenetic processes in fungi. Mycologists have long been fascinated by the morphological and developmental diversity of fruiting bodies; however, e...
The development of sexual fruiting bodies is one of the most complex morphogenetic processes in fungi. Mycologists have long been fascinated by the morphological and developmental diversity of fruiting bodies; however, evolutionary developmental biology of fungi still lags significantly behind that of animals or plants. Here, we summarize the current state of knowledge on fruiting bodies of mushroom-forming Basidiomycota, focusing on phylogenetic and developmental biology. Phylogenetic approaches have revealed a complex history of morphological transformations and convergence in fruiting body morphologies. Frequent transformations and convergence is characteristic of fruiting bodies in contrast to animals or plants, where main body plans are highly conserved. At the same time, insights into the genetic bases of fruiting body development have been achieved using forward and reverse genetic approaches in selected model systems. Phylogenetic and developmental studies of fruiting bodies have each yielded major advances, but they have produced largely disjunct bodies of knowledge. An integrative approach, combining phylogenetic, developmental, and functional biology, is needed to achieve a true fungal evolutionary developmental biology (evo-devo) synthesis for fungal fruiting bodies.
The Peptidyl Transferase Center: a Window to the Past.
Tirumalai MR, Rivas M, Tran Q … +1 more , Fox GE
Microbiol Mol Biol Rev · 2021 Dec · PMID 34756086 · Full text
In his 2001 article, "Translation: in retrospect and prospect," the late Carl Woese made a prescient observation that there was a need for the then-current view of translation to be "reformulated to become an all-embraci...
In his 2001 article, "Translation: in retrospect and prospect," the late Carl Woese made a prescient observation that there was a need for the then-current view of translation to be "reformulated to become an all-embracing perspective about which 21st century Biology can develop" (RNA 7:1055-1067, 2001, https://doi.org/10.1017/s1355838201010615). The quest to decipher the origins of life and the road to the genetic code are both inextricably linked with the history of the ribosome. After over 60 years of research, significant progress in our understanding of how ribosomes work has been made. Particularly attractive is a model in which the ribosome may facilitate an ∼180° rotation of the CCA end of the tRNA from the A-site to the P-site while the acceptor stem of the tRNA would then undergo a translation from the A-site to the P-site. However, the central question of how the ribosome originated remains unresolved. Along the path from a primitive RNA world or an RNA-peptide world to a proto-ribosome world, the advent of the peptidyl transferase activity would have been a seminal event. This functionality is now housed within a local region of the large-subunit (LSU) rRNA, namely, the peptidyl transferase center (PTC). The PTC is responsible for peptide bond formation during protein synthesis and is usually considered to be the oldest part of the modern ribosome. What is frequently overlooked is that by examining the origins of the PTC itself, one is likely going back even further in time. In this regard, it has been proposed that the modern PTC originated from the association of two smaller RNAs that were once independent and now comprise a pseudosymmetric region in the modern PTC. Could such an association have survived? Recent studies have shown that the extant PTC is largely depleted of ribosomal protein interactions. It is other elements like metallic ion coordination and nonstandard base/base interactions that would have had to stabilize the association of RNAs. Here, we present a detailed review of the literature focused on the nature of the extant PTC and its proposed ancestor, the proto-ribosome.
Molecular Mechanisms and Evolutionary Consequences of Spore Killers in Ascomycetes.
Zanders S, Johannesson H
Microbiol Mol Biol Rev · 2021 Dec · PMID 34756084 · Full text
In this review, we examine the fungal spore killers. These are meiotic drive elements that cheat during sexual reproduction to increase their transmission into the next generation. Spore killing has been detected in a nu...
In this review, we examine the fungal spore killers. These are meiotic drive elements that cheat during sexual reproduction to increase their transmission into the next generation. Spore killing has been detected in a number of ascomycete genera, including , , , , and Fusarium. There have been major recent advances in spore killer research that have increased our understanding of the molecular identity, function, and evolutionary history of the known killers. The spore killers vary in the mechanism by which they kill and are divided into killer-target and poison-antidote drivers. In killer-target systems, the drive locus encodes an element that can be described as a killer, while the target is an allele found tightly linked to the drive locus but on the nondriving haplotype. The poison-antidote drive systems encode both a poison and an antidote element within the drive locus. The key to drive in this system is the restricted distribution of the antidote: only the spores that inherit the drive locus receive the antidote and are rescued from the toxicity of the poison. Spore killers also vary in their genome architecture and can consist of a single gene or multiple linked genes. Due to their ability to distort meiosis, spore killers gain a selective advantage at the gene level that allows them to increase in frequency in a population over time, even if they reduce host fitness, and they may have significant impact on genome architecture and macroevolutionary processes such as speciation.
Endoplasmic Reticulum Chaperones in Viral Infection: Therapeutic Perspectives.
Kohli E, Causse S, Baverel V … +4 more , Dubrez L, Borges-Bonan N, Demidov O, Garrido C
Microbiol Mol Biol Rev · 2021 Dec · PMID 34643441 · Full text
Viruses are intracellular parasites that subvert the functions of their host cells to accomplish their infection cycle. The endoplasmic reticulum (ER)-residing chaperone proteins are central for the achievement of differ...
Viruses are intracellular parasites that subvert the functions of their host cells to accomplish their infection cycle. The endoplasmic reticulum (ER)-residing chaperone proteins are central for the achievement of different steps of the viral cycle, from entry and replication to assembly and exit. The most abundant ER chaperones are GRP78 (78-kDa glucose-regulated protein), GRP94 (94-kDa glucose-regulated protein), the carbohydrate or lectin-like chaperones calnexin (CNX) and calreticulin (CRT), the protein disulfide isomerases (PDIs), and the DNAJ chaperones. This review will focus on the pleiotropic roles of ER chaperones during viral infection. We will cover their essential role in the folding and quality control of viral proteins, notably viral glycoproteins which play a major role in host cell infection. We will also describe how viruses co-opt ER chaperones at various steps of their infectious cycle but also in order to evade immune responses and avoid apoptosis. Finally, we will discuss the different molecules targeting these chaperones and the perspectives in the development of broad-spectrum antiviral drugs.
Genetic Networks That Govern Sexual Reproduction in the Pezizomycotina.
Wilson AM, Wilken PM, Wingfield MJ … +1 more , Wingfield BD
Microbiol Mol Biol Rev · 2021 Dec · PMID 34585983 · Full text
Sexual development in filamentous fungi is a complex process that relies on the precise control of and interaction between a variety of genetic networks and pathways. The mating-type () genes are the master regulators of...
Sexual development in filamentous fungi is a complex process that relies on the precise control of and interaction between a variety of genetic networks and pathways. The mating-type () genes are the master regulators of this process and typically act as transcription factors, which control the expression of genes involved at all stages of the sexual cycle. In many fungi, the sexual cycle typically begins when the mating pheromones of one mating type are recognized by a compatible partner, followed by physical interaction and fertilization. Subsequently, highly specialized sexual structures are formed, within which the sexual spores develop after rounds of meiosis and mitosis. These spores are then released and germinate, forming new individuals that initiate new cycles of growth. This review provides an overview of the known genetic networks and pathways that are involved in each major stage of the sexual cycle in filamentous ascomycete fungi.
Sugar-Phosphate Toxicities.
Boulanger EF, Sabag-Daigle A, Thirugnanasambantham P … +2 more , Gopalan V, Ahmer BMM
Microbiol Mol Biol Rev · 2021 Dec · PMID 34585982 · Full text
Accumulation of phosphorylated intermediates during cellular metabolism can have wide-ranging toxic effects on many organisms, including humans and the pathogens that infect them. These toxicities can be induced by feedi...
Accumulation of phosphorylated intermediates during cellular metabolism can have wide-ranging toxic effects on many organisms, including humans and the pathogens that infect them. These toxicities can be induced by feeding an upstream metabolite (a sugar, for instance) while simultaneously blocking the appropriate metabolic pathway with either a mutation or an enzyme inhibitor. Here, we survey the toxicities that can arise in the metabolism of glucose, galactose, fructose, fructose-asparagine, glycerol, trehalose, maltose, mannose, mannitol, arabinose, and rhamnose. Select enzymes in these metabolic pathways may serve as novel therapeutic targets. Some are conserved broadly among prokaryotes and eukaryotes (e.g., glucose and galactose) and are therefore unlikely to be viable drug targets. However, others are found only in bacteria (e.g., fructose-asparagine, rhamnose, and arabinose), and one is found in fungi but not in humans (trehalose). We discuss what is known about the mechanisms of toxicity and how resistance is achieved in order to identify the prospects and challenges associated with targeted exploitation of these pervasive metabolic vulnerabilities.
DNA Repair in .
Ha KP, Edwards AM
Microbiol Mol Biol Rev · 2021 Dec · PMID 34523959 · Full text
Staphylococcus aureus is a common cause of both superficial and invasive infections of humans and animals. Despite a potent host response and apparently appropriate antibiotic therapy, staphylococcal infections frequentl...
Staphylococcus aureus is a common cause of both superficial and invasive infections of humans and animals. Despite a potent host response and apparently appropriate antibiotic therapy, staphylococcal infections frequently become chronic or recurrent, demonstrating a remarkable ability of S. aureus to withstand the hostile host environment. There is growing evidence that staphylococcal DNA repair makes important contributions to the survival of the pathogen in host tissues, as well as promoting the emergence of mutants that resist host defenses and antibiotics. While much of what we know about DNA repair in S. aureus is inferred from studies with model organisms, the roles of specific repair mechanisms in infection are becoming clear and differences with Bacillus subtilis and Escherichia coli have been identified. Furthermore, there is growing interest in staphylococcal DNA repair as a target for novel therapeutics that sensitize the pathogen to host defenses and antibiotics. In this review, we discuss what is known about staphylococcal DNA repair and its role in infection, examine how repair in S. aureus is similar to, or differs from, repair in well-characterized model organisms, and assess the potential of staphylococcal DNA repair as a novel therapeutic target.
Viruses Defined by the Position of the Virosphere within the Replicator Space.
Koonin EV, Dolja VV, Krupovic M … +1 more , Kuhn JH
Microbiol Mol Biol Rev · 2021 Dec · PMID 34468181 · Full text
Originally, viruses were defined as miniscule infectious agents that passed through filters that retain even the smallest cells. Subsequently, viruses were considered obligate intracellular parasites whose reproduction d...
Originally, viruses were defined as miniscule infectious agents that passed through filters that retain even the smallest cells. Subsequently, viruses were considered obligate intracellular parasites whose reproduction depends on their cellular hosts for energy supply and molecular building blocks. However, these features are insufficient to unambiguously define viruses as they are broadly understood today. We outline possible approaches to define viruses and explore the boundaries of the virosphere within the virtual space of replicators and the relationships between viruses and other types of replicators. Regardless of how, exactly, viruses are defined, viruses clearly have evolved on many occasions from nonviral replicators, such as plasmids, by recruiting host proteins to become virion components. Conversely, other types of replicators have repeatedly evolved from viruses. Thus, the virosphere is a dynamic entity with extensive evolutionary traffic across its boundaries. We argue that the virosphere proper, here termed orthovirosphere, consists of a distinct variety of replicators that encode structural proteins encasing the replicators' genomes, thereby providing protection and facilitating transmission among hosts. Numerous and diverse replicators, such as virus-derived but capsidless RNA and DNA elements, or defective viruses occupy the zone surrounding the orthovirosphere in the virtual replicator space. We define this zone as the perivirosphere. Although intense debates on the nature of certain replicators that adorn the internal and external boundaries of the virosphere will likely continue, we present an operational definition of virus that recently has been accepted by the International Committee on Taxonomy of Viruses.
Mating Systems in True Morels ().
Du XH, Yang ZL
Microbiol Mol Biol Rev · 2021 Aug · PMID 34319143 · Full text
True morels ( spp., Morchellaceae, Ascomycota) are widely regarded as a highly prized delicacy and are of great economic and scientific value. Recently, the rapid development of cultivation technology and expansion of ar...
True morels ( spp., Morchellaceae, Ascomycota) are widely regarded as a highly prized delicacy and are of great economic and scientific value. Recently, the rapid development of cultivation technology and expansion of areas for artificial morel cultivation have propelled morel research into a hot topic. Many studies have been conducted in various aspects of morel biology, but despite this, cultivation sites still frequently report failure to fruit or only low production of fruiting bodies. Key problems include the gap between cultivation practices and basic knowledge of morel biology. In this review, in an effort to highlight the mating systems, evolution, and life cycle of morels, we summarize the current state of knowledge of morel sexual reproduction, the structure and evolution of mating-type genes, the sexual process itself, and the influence of mating-type genes on the asexual stages and conidium production. Understanding of these processes is critical for improving technology for the cultivation of morels and for scaling up their commercial production. Morel species may well be good candidates as model species for improving sexual development research in ascomycetes in the future.
The Baltimore Classification of Viruses 50 Years Later: How Does It Stand in the Light of Virus Evolution?
Koonin EV, Krupovic M, Agol VI
Microbiol Mol Biol Rev · 2021 Aug · PMID 34259570 · Full text
Fifty years ago, David Baltimore published a brief conceptual paper delineating the classification of viruses by the routes of genome expression. The six "Baltimore classes" of viruses, with a subsequently added 7th clas...
Fifty years ago, David Baltimore published a brief conceptual paper delineating the classification of viruses by the routes of genome expression. The six "Baltimore classes" of viruses, with a subsequently added 7th class, became the conceptual framework for the development of virology during the next five decades. During this time, it became clear that the Baltimore classes, with relatively minor additions, indeed cover the diversity of virus genome expression schemes that also define the replication cycles. Here, we examine the status of the Baltimore classes 50 years after their advent and explore their links with the global ecology and biology of the respective viruses. We discuss an extension of the Baltimore scheme and why many logically admissible expression-replication schemes do not appear to be realized in nature. Recent phylogenomic analyses allow tracing the complex connections between the Baltimore classes and the monophyletic realms of viruses. The five classes of RNA viruses and reverse-transcribing viruses share an origin, whereas both the single-stranded DNA viruses and double-stranded DNA (dsDNA) viruses evolved on multiple independent occasions. Most of the Baltimore classes of viruses probably emerged during the earliest era of life evolution, at the stage of the primordial pool of diverse replicators, and before the advent of modern-like cells with large dsDNA genomes. The Baltimore classes remain an integral part of the conceptual foundation of biology, providing the essential structure for the logical space of information transfer processes, which is nontrivially connected with the routes of evolution of viruses and other replicators.
How the PhoP/PhoQ System Controls Virulence and Mg Homeostasis: Lessons in Signal Transduction, Pathogenesis, Physiology, and Evolution.
Groisman EA, Duprey A, Choi J
Microbiol Mol Biol Rev · 2021 Aug · PMID 34191587 · Full text
The PhoP/PhoQ two-component system governs virulence, Mg homeostasis, and resistance to a variety of antimicrobial agents, including acidic pH and cationic antimicrobial peptides, in several Gram-negative bacterial speci...
The PhoP/PhoQ two-component system governs virulence, Mg homeostasis, and resistance to a variety of antimicrobial agents, including acidic pH and cationic antimicrobial peptides, in several Gram-negative bacterial species. Best understood in Salmonella enterica serovar Typhimurium, the PhoP/PhoQ system consists o-regulated gene products alter PhoP-P amounts, even under constant inducing conditions. PhoP-P controls the abundance of hundreds of proteins both directly, by having transcriptional effects on the corresponding genes, and indirectly, by modifying the abundance, activity, or stability of other transcription factors, regulatory RNAs, protease regulators, and metabolites. The investigation of PhoP/PhoQ has uncovered novel forms of signal transduction and the physiological consequences of regulon evolution.
On a Special Collection in MMBR on Sex in Fungi: Molecular Mechanisms and Evolutionary Implications.
Butler G, Heitman J, Idnurm A … +1 more , James TY
Microbiol Mol Biol Rev · 2021 Aug · PMID 34132102 · Full text
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Pneumocystis Mating-Type Locus and Sexual Cycle during Infection.
Hauser PM
Microbiol Mol Biol Rev · 2021 Aug · PMID 34132101 · Full text
Pneumocystis species colonize mammalian lungs and cause deadly pneumonia if the immune system of the host weakens. Each species presents a specificity for a single mammalian host species. Pneumocystis jirovecii infects h...
Pneumocystis species colonize mammalian lungs and cause deadly pneumonia if the immune system of the host weakens. Each species presents a specificity for a single mammalian host species. Pneumocystis jirovecii infects humans and provokes pneumonia, which is among the most frequent invasive fungal infections. The lack of culture methods for these fungi complicates their study. Recently, high-throughput sequencing technologies followed by comparative genomics have allowed a better understanding of the mechanisms involved in the sexuality of Pneumocystis organisms. The structure of their mating-type locus corresponding to a fusion of two loci, Plus and Minus, and the concomitant expression of the three mating-type genes revealed that their mode of sexual reproduction is primarily homothallism. This mode is favored by microbial pathogens and involves a single self-compatible mating type that can enter into the sexual cycle on its own. Pneumocystis sexuality is obligatory within the host's lungs during pneumonia in adults, primary infection in children, and possibly colonization. This sexuality participates in cell proliferation, airborne transmission to new hosts, and probably antigenic variation, processes that are crucial to ensure the survival of the fungus. Thus, sexuality is central in the Pneumocystis life cycle. The obligate biotrophic parasitism with obligate sexuality of Pneumocystis is unique among fungi pathogenic to humans. Pneumocystis organisms are similar to the plant fungal obligate biotrophs that complete their entire life cycle within their hosts, including sex, and that are also difficult to grow .
The Classical, Yet Controversial, First Enzyme of Lipid Synthesis: Escherichia coli Acetyl-CoA Carboxylase.
Cronan JE
Microbiol Mol Biol Rev · 2021 Aug · PMID 34132100 · Full text
Escherichia coli acetyl-CoA carboxylase (ACC), the enzyme responsible for synthesis of malonyl-CoA, the building block of fatty acid synthesis, is the paradigm bacterial ACC. Many reports on the structures and stoichiome...
Escherichia coli acetyl-CoA carboxylase (ACC), the enzyme responsible for synthesis of malonyl-CoA, the building block of fatty acid synthesis, is the paradigm bacterial ACC. Many reports on the structures and stoichiometry of the four subunits comprising the active enzyme as well as on regulation of ACC activity and expression have appeared in the almost 20 years since this subject was last reviewed. This review seeks to update and expand on these reports.
Large Clostridial Toxins: Mechanisms and Roles in Disease.
Orrell KE, Melnyk RA
Microbiol Mol Biol Rev · 2021 Aug · PMID 34076506 · Full text
Large clostridial toxins (LCTs) are a family of bacterial exotoxins that infiltrate and destroy target cells. Members of the LCT family include Clostridioides difficile toxins TcdA and TcdB, Paeniclostridium sordellii to...
Large clostridial toxins (LCTs) are a family of bacterial exotoxins that infiltrate and destroy target cells. Members of the LCT family include Clostridioides difficile toxins TcdA and TcdB, Paeniclostridium sordellii toxins TcsL and TcsH, Clostridium novyi toxin TcnA, and Clostridium perfringens toxin TpeL. Since the 19th century, LCT-secreting bacteria have been isolated from the blood, organs, and wounds of diseased individuals, and LCTs have been implicated as the primary virulence factors in a variety of infections, including C. difficile infection and some cases of wound-associated gas gangrene. Clostridia express and secrete LCTs in response to various physiological signals. LCTs invade host cells by binding specific cell surface receptors, ultimately leading to internalization into acidified vesicles. Acidic pH promotes conformational changes within LCTs, which culminates in translocation of the N-terminal glycosyltransferase and cysteine protease domain across the endosomal membrane and into the cytosol, leading first to cytopathic effects and later to cytotoxic effects. The focus of this review is on the role of LCTs in infection and disease, the mechanism of LCT intoxication, with emphasis on recent structural work and toxin subtyping analysis, and the genomic discovery and characterization of LCT homologues. We provide a comprehensive review of these topics and offer our perspective on emerging questions and future research directions for this enigmatic family of toxins.
Endogenous and Borrowed Proteolytic Activity in the .
Coleman JL, Benach JL, Karzai AW
Microbiol Mol Biol Rev · 2021 May · PMID 33980587 · Full text
The spp. are tick-borne pathogenic spirochetes that include the agents of Lyme disease and relapsing fever. As part of their life cycle, the spirochetes traffic between the tick vector and the vertebrate host, which req...
The spp. are tick-borne pathogenic spirochetes that include the agents of Lyme disease and relapsing fever. As part of their life cycle, the spirochetes traffic between the tick vector and the vertebrate host, which requires significant physiological changes and remodeling of their outer membranes and proteome. This crucial proteome resculpting is carried out by a diverse set of proteases, adaptor proteins, and related chaperones. Despite its small genome, has dedicated a large percentage of its genome to proteolysis, including a full complement of ATP-dependent proteases. Energy-driven proteolysis appears to be an important physiological feature of this dual-life-cycle bacterium. The proteolytic arsenal of is strategically deployed for disposal of proteins no longer required as they move from one stage to another or are transferred from one host to another. Likewise, the spp. are systemic organisms that need to break down and move through host tissues and barriers, and so their unique proteolytic resources, both endogenous and borrowed, make movement more feasible. Both the Lyme disease and relapsing fever spp. bind plasminogen as well as numerous components of the mammalian plasminogen-activating system. This recruitment capacity endows the spirochetes with a borrowed proteolytic competency that can lead to increased invasiveness.
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