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Listeria monocytogenes: towards a complete picture of its physiology and pathogenesis
Listeria monocytogenes is a food-borne pathogen responsible for a disease called listeriosis, which is potentially lethal in immunocompromised individuals. This bacterium, first used as a model to study cell-mediated immunity, has emerged over the past 20 years as a paradigm in infection biology, cell biology and fundamental microbiology. In this Review, we highlight recent advances in the understanding of human listeriosis and L. monocytogenes biology. We describe unsuspected modes of hijacking host cell biology, ranging from changes in organelle morphology to direct effects on host transcription via a new class of bacterial effectors called nucleomodulins. We then discuss advances in understanding infection in vivo, including the discovery of tissue-specific virulence factors and the 'arms race' among bacteria competing for a niche in the microbiota. Finally, we describe the complexity of bacterial regulation and physiology, incorporating new insights into the mechanisms of action of a series of riboregulators that are critical for efficient metabolic regulation, antibiotic resistance and interspecies competition.
Journal Article
Streptococcus pneumoniae: transmission, colonization and invasion
Streptococcus pneumoniae has a complex relationship with its obligate human host. On the one hand, the pneumococci are highly adapted commensals, and their main reservoir on the mucosal surface of the upper airways of carriers enables transmission. On the other hand, they can cause severe disease when bacterial and host factors allow them to invade essentially sterile sites, such as the middle ear spaces, lungs, bloodstream and meninges. Transmission, colonization and invasion depend on the remarkable ability of S. pneumoniae to evade or take advantage of the host inflammatory and immune responses. The different stages of pneumococcal carriage and disease have been investigated in detail in animal models and, more recently, in experimental human infection. Furthermore, widespread vaccination and the resulting immune pressure have shed light on pneumococcal population dynamics and pathogenesis. Here, we review the mechanistic insights provided by these studies on the multiple and varied interactions of the pneumococcus and its host.
Journal Article
كاليجولا : مسرحية
كتب \"ألبير\" مسرحية \"كاليجولا\" عام 1938 وهو في حسن الخامسة والعشرين، وإلى يومنا هذا يعدها النقاد أفضل مسرحياته وبالإضافة إلى كونها أكثر إثارة للجدل والشهرة، نجد فيها عصيانا شيطانيا ضد القدر، قدمه لنا مؤلفها وهو في الطريق للبحث عن معالجة لمشكلة الحرية ولذا أقدم كامو على اختيار حاكم مطلق كبطل لمسرحيته هذه، هو الذي يشرع القوانين، وهو الذي يخرقها ويبدل فيها كما تهوى نفسه، وغالبا ما يزدريها، متباهيا بأنه لم يتوقف قط عن تعليم قومه دروسا في الحرية.
Book
Interactions of commensal and pathogenic microorganisms with the intestinal mucosal barrier
The intestinal mucosal barrier is composed of epithelial cells that are protected by an overlying host-secreted mucous layer and functions as the first line of defence against pathogenic and non-pathogenic microorganisms. Some microorganisms have evolved strategies to either survive in the mucosal barrier or circumvent it to establish infection. In this Review, we discuss the current state of knowledge of the complex interactions of commensal microorganisms with the intestinal mucosal barrier, and we discuss strategies used by pathogenic microorganisms to establish infection by either exploiting different epithelial cell lineages or disrupting the mucous layer, as well as the role of defects in mucus production in chronic disease.
Journal Article
Caligula : The Abuse of Power
\"In this book about Rome's most infamous emperor, expert author, Stephen Dando-Collins' chronicles all the palace intrigues and murders that led to Caligula becoming emperor, and details the horrors of his manic reign and the murderous consequences brought about at the hand of his sister Agrippina the Younger, his uncle Claudius and his nephew Nero.\"--Provided by publisher.
Book
Outer-membrane vesicles from Gram-negative bacteria: biogenesis and functions
Key Points
Vesicles derived from the outer membrane of Gram-negative bacteria, or outer-membrane vesicles (OMVs), are heterogeneous in size and composition, encapsulate soluble periplasmic content and are ubiquitously produced. The difficulty in finding a single molecular or genetic basis for OMV production is probably due to species-dependent differences in envelope architecture, environmental influences on envelope composition and redundancy of OMV-producing pathways.
Mutations that subtly affect envelope crosslinking affect OMV production, whereas bacterial mutants that are unable to crosslink the envelope are typically unstable and form lysis products instead of OMVs. Lipopolysaccharide (LPS) subtypes also affect the levels of OMV production, as well as OMV cargo recruitment.
OMV cargo may be enriched or excluded compared with its abundance in the bacterial envelope, suggesting that cargo recruitment is a regulated rather than stochastic process. Well-characterized cargoes include virulence factors, antibiotic-degrading enzymes, surface adherence factors, proteases and enzymes that are important for nutrient acquisition.
OMVs can serve in bacterial communities as 'public goods' by distributing enzymes that break down extracellular material into nutrients, by recruiting iron, by acting as decoys for bacteriophages or antibiotics and by transferring DNA between cells.
The versatile characteristics of OMVs and their immunomodulatory properties can be exploited for bioengineering applications and vaccine development.
In this Review, Schwechheimer and Kuehn describe recent developments in elucidating the mechanisms of biogenesis and cargo selection of the outer-membrane vesicles (OMVs) produced by Gram-negative bacteria. They also discuss the functions of OMVs in bacterial physiology and during pathogenesis.
Outer-membrane vesicles (OMVs) are spherical buds of the outer membrane filled with periplasmic content and are commonly produced by Gram-negative bacteria. The production of OMVs allows bacteria to interact with their environment, and OMVs have been found to mediate diverse functions, including promoting pathogenesis, enabling bacterial survival during stress conditions and regulating microbial interactions within bacterial communities. Additionally, because of this functional versatility, researchers have begun to explore OMVs as a platform for bioengineering applications. In this Review, we discuss recent advances in the study of OMVs, focusing on new insights into the mechanisms of biogenesis and the functions of these vesicles.
Journal Article
Claudius
\"Claudius became emperor after the assassination of Caligula, and was deified by his successor Nero in AD 54. Opinions of him have varied greatly over succeeding centuries, but he has mostly been caricatured as a reluctant emperor, hampered by a speech impediment, who preferred reading to ruling. Barbara Levick's authoritative study reassesses the reign of Claudius, examining his political objectives and activities within the constitutional, political, social and economic development of Rome. Out of Levick's critical scrutiny of the literary, archaeological and epigraphic sources emerges a different Claudius -- an intelligent politician, ruthlessly determined to secure his position as ruler. Now updated to take account of recent scholarship, Claudius remains essential reading for students and historians of the early Roman Empire\"-- Provided by publisher.
Book
The mycobacterial cell envelope — a moving target
Mycobacterium tuberculosis, the leading cause of death due to infection, has a dynamic and immunomodulatory cell envelope. The cell envelope structurally and functionally varies across the length of the cell and during the infection process. This variability allows the bacterium to manipulate the human immune system, tolerate antibiotic treatment and adapt to the variable host environment. Much of what we know about the mycobacterial cell envelope has been gleaned from model actinobacterial species, or model conditions such as growth in vitro, in macrophages and in the mouse. In this Review, we combine data from different experimental systems to build a model of the dynamics of the mycobacterial cell envelope across space and time. We describe the regulatory pathways that control metabolism of the cell wall and surface lipids in M. tuberculosis during growth and stasis, and speculate about how this regulation might affect antibiotic susceptibility and interactions with the immune system.
Journal Article