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Evolutionary trajectory for nuclear functions of ciliary transport complex proteins.

Ewerling A, May-Simera HL

Microbiol Mol Biol Rev · 2024 Sep · PMID 38995044 · Full text

SUMMARYCilia and the nucleus were two defining features of the last eukaryotic common ancestor. In early eukaryotic evolution, these structures evolved through the diversification of a common membrane-coating ancestor, t... SUMMARYCilia and the nucleus were two defining features of the last eukaryotic common ancestor. In early eukaryotic evolution, these structures evolved through the diversification of a common membrane-coating ancestor, the protocoatomer. While in cilia, the descendants of this protein complex evolved into parts of the intraflagellar transport complexes and BBSome, the nucleus gained its selectivity by recruiting protocoatomer-like proteins to the nuclear envelope to form the selective nuclear pore complexes. Recent studies show a growing number of proteins shared between the proteomes of the respective organelles, and it is currently unknown how ciliary transport proteins could acquire nuclear functions and . The nuclear functions of ciliary proteins are still observable today and remain relevant for the understanding of the disease mechanisms behind ciliopathies. In this work, we review the evolutionary history of cilia and nucleus and their respective defining proteins and integrate current knowledge into theories for early eukaryotic evolution. We postulate a scenario where both compartments co-evolved and that fits current models of eukaryotic evolution, explaining how ciliary proteins and nucleoporins acquired their dual functions.

Mechanisms of action of microbicides commonly used in infection prevention and control.

Gerba CP, Boone S, Nims RW … +5 more , Maillard J-Y, Sattar SA, Rubino JR, McKinney J, Ijaz MK

Microbiol Mol Biol Rev · 2024 Sep · PMID 38958456 · Full text

SUMMARYUnderstanding how commonly used chemical microbicides affect pathogenic microorganisms is important for formulation of microbicides. This review focuses on the mechanism(s) of action of chemical microbicides commo... SUMMARYUnderstanding how commonly used chemical microbicides affect pathogenic microorganisms is important for formulation of microbicides. This review focuses on the mechanism(s) of action of chemical microbicides commonly used in infection prevention and control. Contrary to the typical site-specific mode of action of antibiotics, microbicides often act via multiple targets, causing rapid and irreversible damage to microbes. In the case of viruses, the envelope or protein capsid is usually the primary structural target, resulting in loss of envelope integrity or denaturation of proteins in the capsid, causing loss of the receptor-binding domain for host cell receptors, and/or breakdown of other viral proteins or nucleic acids. However, for certain virucidal microbicides, the nucleic acid may be a significant site of action. The region of primary damage to the protein or nucleic acid is site-specific and may vary with the virus type. Due to their greater complexity and metabolism, bacteria and fungi offer more targets. The rapid and irreversible damage to microbes may result from solubilization of lipid components and denaturation of enzymes involved in the transport of nutrients. Formulation of microbicidal actives that attack multiple sites on microbes, or control of the pH, addition of preservatives or potentiators, and so on, can increase the spectrum of action against pathogens and reduce both the concentrations and times needed to achieve microbicidal activity against the target pathogens.

Molecular determinants of cross-species transmission in emerging viral infections.

Wickenhagen A, van Tol S, Munster V

Microbiol Mol Biol Rev · 2024 Sep · PMID 38912755 · Full text

SUMMARYSeveral examples of high-impact cross-species transmission of newly emerging or re-emerging bat-borne viruses, such as Sudan virus, Nipah virus, and severe acute respiratory syndrome coronavirus 2, have occurred i... SUMMARYSeveral examples of high-impact cross-species transmission of newly emerging or re-emerging bat-borne viruses, such as Sudan virus, Nipah virus, and severe acute respiratory syndrome coronavirus 2, have occurred in the past decades. Recent advancements in next-generation sequencing have strengthened ongoing efforts to catalog the global virome, in particular from the multitude of different bat species. However, functional characterization of these novel viruses and virus sequences is typically limited with regard to assessment of their cross-species potential. Our understanding of the intricate interplay between virus and host underlying successful cross-species transmission has focused on the basic mechanisms of entry and replication, as well as the importance of host innate immune responses. In this review, we discuss the various roles of the respective molecular mechanisms underlying cross-species transmission using different recent bat-borne viruses as examples. To delineate the crucial cellular and molecular steps underlying cross-species transmission, we propose a framework of overall characterization to improve our capacity to characterize viruses as benign, of interest, or of concern.

Membrane and organelle rearrangement during ascospore formation in budding yeast.

Neiman AM

Microbiol Mol Biol Rev · 2024 Sep · PMID 38899894 · Full text

SUMMARYIn ascomycete fungi, sexual spores, termed ascospores, are formed after meiosis. Ascospore formation is an unusual cell division in which daughter cells are created within the cytoplasm of the mother cell by gene... SUMMARYIn ascomycete fungi, sexual spores, termed ascospores, are formed after meiosis. Ascospore formation is an unusual cell division in which daughter cells are created within the cytoplasm of the mother cell by generation of membranes that encapsulate each of the haploid chromosome sets created by meiosis. This review describes the molecular events underlying the creation, expansion, and closure of these membranes in the budding yeast, . Recent advances in our understanding of the regulation of gene expression and the dynamic behavior of different membrane-bound organelles during this process are detailed. While less is known about ascospore formation in other systems, comparison to the distantly related fission yeast suggests that the molecular events will be broadly similar throughout the ascomycetes.

An in-depth exploration of the multifaceted roles of EVs in the context of pathogenic single-cell microorganisms.

Feix AS, Tabaie EZ, Singh AN … +3 more , Wittenberg NJ, Wilson EH, Joachim A

Microbiol Mol Biol Rev · 2024 Sep · PMID 38869292 · Full text

SUMMARYExtracellular vesicles (EVs) have been recognized throughout scientific communities as potential vehicles of intercellular communication in both eukaryotes and prokaryotes, thereby influencing various physiologica... SUMMARYExtracellular vesicles (EVs) have been recognized throughout scientific communities as potential vehicles of intercellular communication in both eukaryotes and prokaryotes, thereby influencing various physiological and pathological functions of both parent and recipient cells. This review provides an in-depth exploration of the multifaceted roles of EVs in the context of bacteria and protozoan parasite EVs, shedding light on their contributions to physiological processes and disease pathogenesis. These studies highlight EVs as a conserved mechanism of cellular communication, which may lead us to important breakthroughs in our understanding of infection, mechanisms of pathogenesis, and as indicators of disease. Furthermore, EVs are involved in host-microbe interactions, offering insights into the strategies employed by bacteria and protozoan parasites to modulate host responses, evade the immune system, and establish infections.

The biology and pathogenicity of type F: a common human enteropathogen with a new(ish) name.

Shrestha A, Mehdizadeh Gohari I, Li J … +3 more , Navarro M, Uzal FA, McClane BA

Microbiol Mol Biol Rev · 2024 Sep · PMID 38864615 · Full text

SUMMARYIn the 2018-revised typing classification system, isolates carrying the enterotoxin () and alpha toxin genes but no other typing toxin genes are now designated as type F. Type F isolates cause food poisoning and... SUMMARYIn the 2018-revised typing classification system, isolates carrying the enterotoxin () and alpha toxin genes but no other typing toxin genes are now designated as type F. Type F isolates cause food poisoning and nonfoodborne human gastrointestinal (GI) diseases, which most commonly involve type F isolates carrying, respectivefooly, a chromosomal or plasmid-borne gene. Compared to spores of other isolates, spores of type F chromosomal isolates often exhibit greater resistance to food environment stresses, likely facilitating their survival in improperly prepared or stored foods. Multiple factors contribute to this spore resistance phenotype, including the production of a variant small acid-soluble protein-4. The pathogenicity of type F isolates involves sporulation-dependent enterotoxin (CPE) production. sporulation is initiated by orphan histidine kinases and sporulation-associated sigma factors that drive transcription. CPE-induced cytotoxicity starts when CPE binds to claudin receptors to form a small complex (which also includes nonreceptor claudins). Approximately six small complexes oligomerize on the host cell plasma membrane surface to form a prepore. CPE molecules in that prepore apparently extend β-hairpin loops to form a β-barrel pore, allowing a Ca influx that activates calpain. With low-dose CPE treatment, caspase-3-dependent apoptosis develops, while high-CPE dose treatment induces necroptosis. Those effects cause histologic damage along with fluid and electrolyte losses from the colon and small intestine. Sialidases likely contribute to type F disease by enhancing CPE action and, for NanI-producing nonfoodborne human GI disease isolates, increasing intestinal growth and colonization.

Bacterial cell volume regulation and the importance of cyclic di-AMP.

Foster AJ, van den Noort M, Poolman B

Microbiol Mol Biol Rev · 2024 Jun · PMID 38856222 · Full text

SUMMARYNucleotide-derived second messengers are present in all domains of life. In prokaryotes, most of their functionality is associated with general lifestyle and metabolic adaptations, often in response to environment... SUMMARYNucleotide-derived second messengers are present in all domains of life. In prokaryotes, most of their functionality is associated with general lifestyle and metabolic adaptations, often in response to environmental fluctuations of physical parameters. In the last two decades, cyclic di-AMP has emerged as an important signaling nucleotide in many prokaryotic lineages, including Firmicutes, Actinobacteria, and Cyanobacteria. Its importance is highlighted by the fact that both the lack and overproduction of cyclic di-AMP affect viability of prokaryotes that utilize cyclic di-AMP, and that it generates a strong innate immune response in eukaryotes. In bacteria that produce the second messenger, most molecular targets of cyclic di-AMP are associated with cell volume control. Besides, other evidence links the second messenger to cell wall remodeling, DNA damage repair, sporulation, central metabolism, and the regulation of glycogen turnover. In this review, we take a biochemical, quantitative approach to address the main cellular processes that are directly regulated by cyclic di-AMP and show that these processes are very connected and require regulation of a similar set of proteins to which cyclic di-AMP binds. Altogether, we argue that cyclic di-AMP is a master regulator of cell volume and that other cellular processes can be connected with cyclic di-AMP through this core function. We further highlight important directions in which the cyclic di-AMP field has to develop to gain a full understanding of the cyclic di-AMP signaling network and why some processes are regulated, while others are not.

and : global priority pathogens.

Katsipoulaki M, Stappers MHT, Malavia-Jones D … +3 more , Brunke S, Hube B, Gow NAR

Microbiol Mol Biol Rev · 2024 Jun · PMID 38832801 · Full text

SUMMARYA significant increase in the incidence of -mediated infections has been observed in the last decade, mainly due to rising numbers of susceptible individuals. Recently, the World Health Organization published its... SUMMARYA significant increase in the incidence of -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 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 and . Of these, is the most common cause of candidemia around the world and is categorized as a critical priority pathogen. 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.

Genotypic diversity, virulence, and molecular genetic tools in .

Sepúlveda VE, Goldman WE, Matute DR

Microbiol Mol Biol Rev · 2024 Jun · PMID 38819148 · Full text

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 dis... 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. , 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. and histoplasmosis have been classified as being of emergent importance, and in 2022, the World Health Organization included 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 . 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.

CRISPRi functional genomics in bacteria and its application to medical and industrial research.

Enright AL, Heelan WJ, Ward RD … +1 more , Peters JM

Microbiol Mol Biol Rev · 2024 Jun · PMID 38809084 · Full text

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... 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.

Lipoic acid attachment to proteins: stimulating new developments.

Cronan JE

Microbiol Mol Biol Rev · 2024 Jun · PMID 38624243 · Full text

SUMMARYLipoic acid-modified proteins are essential for central metabolism and pathogenesis. In recent years, the and lipoyl assembly pathways have been modified and extended to archaea and diverse eukaryotes including... SUMMARYLipoic acid-modified proteins are essential for central metabolism and pathogenesis. In recent years, the and lipoyl assembly pathways have been modified and extended to archaea and diverse eukaryotes including humans. These extensions include a new pathway to insert the key sulfur atoms of lipoate, several new pathways of lipoate salvage, and a novel use of lipoic acid in sulfur-oxidizing bacteria. Other advances are the modification of LplA for studies of protein localization and protein-protein interactions in cell biology and in enzymatic removal of lipoate from lipoyl proteins. Finally, scenarios have been put forth for the evolution of lipoate assembly in archaea.

Retracing the evolution of species, with a focus on the human pathogen .

Cissé OH, Ma L, Kovacs JA

Microbiol Mol Biol Rev · 2024 Jun · PMID 38587383 · Full text

SUMMARYEvery human being is presumed to be infected by the fungus at least once in his or her lifetime. This fungus belongs to a large group of species that appear to exclusively infect mammals, with being the only one... SUMMARYEvery human being is presumed to be infected by the fungus at least once in his or her lifetime. This fungus belongs to a large group of species that appear to exclusively infect mammals, with being the only one known to cause disease in humans. The mystery of origin and speciation is just beginning to unravel. Here, we provide a review of the major steps of evolution. The genus likely originated from soil or plant-associated organisms during the period of Cretaceous ~165 million years ago and successfully shifted to mammals. The transition coincided with a substantial loss of genes, many of which are related to the synthesis of nutrients that can be scavenged from hosts or cell wall components that could be targeted by the mammalian immune system. Following the transition, the genus cospeciated with mammals. Each species specialized at infecting its own host. Host specialization is presumably built at least partially upon surface glycoproteins, whose protogene was acquired prior to the genus formation. appeared at ~65 million years ago, overlapping with the emergence of the first primates. and its sister species , which infects macaques nowadays, may have had overlapping host ranges in the distant past. Clues from molecular clocks suggest that did not cospeciate with humans. Molecular evidence suggests that speciation involved chromosomal rearrangements and the mounting of genetic barriers that inhibit gene flow among species.

stress-associated mutagenesis and developmental DNA repair.

Pedraza-Reyes M, Abundiz-Yañez K, Rangel-Mendoza A … +7 more , Martínez LE, Barajas-Ornelas RC, Cuéllar-Cruz M, Leyva-Sánchez HC, Ayala-García VM, Valenzuela-García LI, Robleto EA

Microbiol Mol Biol Rev · 2024 Jun · PMID 38551349 · Full text

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... 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) 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.

Structural analysis of resistance-nodulation cell division transporters.

Klenotic PA, Yu EW

Microbiol Mol Biol Rev · 2024 Jun · PMID 38551344 · Full text

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... 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.

White-opaque switching in : cell biology, regulation, and function.

Soll DR

Microbiol Mol Biol Rev · 2024 Jun · PMID 38546228 · Full text

SUMMARY remains a major fungal pathogen colonizing humans and opportunistically invading tissue when conditions are predisposing. Part of the success of was attributed to its capacity to form hyphae that facilitate tiss... SUMMARY remains a major fungal pathogen colonizing humans and opportunistically invading tissue when conditions are predisposing. Part of the success of 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 . For the 15 years following the discovery of white-opaque switching, its role in the biology of remained elusive. Then in 2002, it was discovered that in order to mate, 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 , 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.

Hsp90, a team player in protein quality control and the stress response in bacteria.

Wickramaratne AC, Wickner S, Kravats AN

Microbiol Mol Biol Rev · 2024 Jun · PMID 38534118 · Full text

SUMMARYHeat shock protein 90 (Hsp90) participates in proteostasis by facilitating protein folding, activation, disaggregation, prevention of aggregation, degradation, and protection against degradation of various cellula... SUMMARYHeat shock protein 90 (Hsp90) participates in proteostasis by facilitating protein folding, activation, disaggregation, prevention of aggregation, degradation, and protection against degradation of various cellular proteins. It is highly conserved from bacteria to humans. In bacteria, protein remodeling by Hsp90 involves collaboration with the Hsp70 molecular chaperone and Hsp70 cochaperones. In eukaryotes, protein folding by Hsp90 is more complex and involves collaboration with many Hsp90 cochaperones as well as Hsp70 and Hsp70 cochaperones. This review focuses primarily on bacterial Hsp90 and highlights similarities and differences between bacterial and eukaryotic Hsp90. Seminal research findings that elucidate the structure and the mechanisms of protein folding, disaggregation, and reactivation promoted by Hsp90 are discussed. Understanding the mechanisms of bacterial Hsp90 will provide fundamental insight into the more complex eukaryotic chaperone systems.

Insights into the enigma of oral streptococci in carcinogenesis.

Senthil Kumar S, Johnson MDL, Wilson JE

Microbiol Mol Biol Rev · 2024 Jun · PMID 38506551 · Full text

SUMMARYThe genus 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 viridans... SUMMARYThe genus 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 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.

From isotopically labeled DNA to fluorescently labeled dynamic pili: building a mechanistic model of DNA transport to the cytoplasmic membrane.

Zuke JD, Burton BM

Microbiol Mol Biol Rev · 2024 Mar · PMID 38466096 · Full text

SUMMARYNatural competence, the physiological state wherein bacteria produce proteins that mediate extracellular DNA transport into the cytosol and the subsequent recombination of DNA into the genome, is conserved across... SUMMARYNatural competence, the physiological state wherein bacteria produce proteins that mediate extracellular DNA transport into the cytosol and the subsequent recombination of DNA into the genome, is conserved across the bacterial domain. DNA must successfully translocate across formidable permeability barriers during import, including the cell membrane(s) and the cell wall, that are normally impermeable to large DNA polymers. This review will examine the mechanisms underlying DNA transport from the extracellular space to the cytoplasmic membrane. First, the challenges inherent to DNA movement through the cell periphery will be discussed to provide context for DNA transport during natural competence. The following sections will trace the development of a comprehensive model for DNA translocation to the cytoplasmic membrane, highlighting the crucial studies performed over the last century that have contributed to building contemporary DNA import models. Finally, this review will conclude by reflecting on what is still unknown about the process and the possible solutions to overcome these limitations.

Interplay between group A and host innate immune responses.

Su MS-W, Cheng Y-L, Lin Y-S … +1 more , Wu J-J

Microbiol Mol Biol Rev · 2024 Mar · PMID 38451081 · Full text

SUMMARYGroup A (GAS), also known as , is a clinically well-adapted human pathogen that harbors rich virulence determinants contributing to a broad spectrum of diseases. GAS is capable of invading epithelial, endothelial... SUMMARYGroup A (GAS), also known as , is a clinically well-adapted human pathogen that harbors rich virulence determinants contributing to a broad spectrum of diseases. GAS is capable of invading epithelial, endothelial, and professional phagocytic cells while evading host innate immune responses, including phagocytosis, selective autophagy, light chain 3-associated phagocytosis, and inflammation. However, without a more complete understanding of the different ways invasive GAS infections develop, it is difficult to appreciate how GAS survives and multiplies in host cells that have interactive immune networks. This review article attempts to provide an overview of the behaviors and mechanisms that allow pathogenic GAS to invade cells, along with the strategies that host cells practice to constrain GAS infection. We highlight the counteractions taken by GAS to apply virulence factors such as streptolysin O, nicotinamide-adenine dinucleotidase, and streptococcal pyrogenic exotoxin B as a hindrance to host innate immune responses.

Molecular mechanisms that govern infection and antifungal resistance in Mucorales.

Lax C, Nicolás FE, Navarro E … +1 more , Garre V

Microbiol Mol Biol Rev · 2024 Mar · PMID 38445820 · Full text

SUMMARYThe World Health Organization has established a fungal priority pathogens list that includes species critical or highly important to human health. Among them is the order Mucorales, a fungal group comprising at le... SUMMARYThe World Health Organization has established a fungal priority pathogens list that includes species critical or highly important to human health. Among them is the order Mucorales, a fungal group comprising at least 39 species responsible for the life-threatening infection known as mucormycosis. Despite the continuous rise in cases and the poor prognosis due to innate resistance to most antifungal drugs used in the clinic, Mucorales has received limited attention, partly because of the difficulties in performing genetic manipulations. The COVID-19 pandemic has further escalated cases, with some patients experiencing the COVID-19-associated mucormycosis, highlighting the urgent need to increase knowledge about these fungi. This review addresses significant challenges in treating the disease, including delayed and poor diagnosis, the lack of accurate global incidence estimation, and the limited treatment options. Furthermore, it focuses on the most recent discoveries regarding the mechanisms and genes involved in the development of the disease, antifungal resistance, and the host defense response. Substantial advancements have been made in identifying key fungal genes responsible for invasion and tissue damage, host receptors exploited by the fungus to invade tissues, and mechanisms of antifungal resistance. This knowledge is expected to pave the way for the development of new antifungals to combat mucormycosis. In addition, we anticipate significant progress in characterizing Mucorales biology, particularly the mechanisms involved in pathogenesis and antifungal resistance, with the possibilities offered by CRISPR-Cas9 technology for genetic manipulation of the previously intractable Mucorales species.
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