The transcription factor DksA exerts opposing effects on cell division depending on the presence of ppGpp.

Cell division is a key step in the bacterial lifecycle that must be appropriately regulated to ensure survival. This work identifies the alarmone (p)ppGpp (ppGpp) as a general regulator of cell division, extending our understanding of the role of ppGpp beyond a signal for starvation and other stress. Even in nutrient-replete conditions, basal levels of ppGpp are essential for division to occur appropriately and for cell size to be maintained.

The transcription factor DksA exerts opposing effects on cell division depending on the presence of ppGpp.

Unlabelled: Bacterial cell size is a multifactorial trait that is influenced by variables including nutritional availability and the timing of cell division. Prior work revealed a negative correlation between the alarmone (p)ppGpp (ppGpp) and cell length in , suggesting that ppGpp may promote assembly of the division machinery (divisome) and cytokinesis in this organism. To clarify this counterintuitive connection between a starvation induced stress response effector and cell proliferation, we undertook a systematic analysis of growth and division in cells defective in ppGpp synthesis and/or engineered to overproduce the alarmone.

A listeriolysin O subunit vaccine is protective against Listeria monocytogenes.

Listeria monocytogenes is a facultative intracellular pathogen responsible for the life-threatening disease listeriosis. The pore-forming toxin listeriolysin O (LLO) is a critical virulence factor that plays a major role in the L. monocytogenes intracellular lifecycle and is indispensable for pathogenesis.

The Absence of (p)ppGpp Renders Initiation of Escherichia coli Chromosomal DNA Synthesis Independent of Growth Rates.

The initiation of chromosomal DNA replication starts with the oligomerization of the DnaA protein at repeat sequences within the origin () region. The amount of DNA per cell directly correlates with the growth rate. During fast growth, the cell generation time is shorter than the time required for complete DNA replication; therefore, overlapping rounds of chromosome replication are required.

Mechanistic Origin of Cell-Size Control and Homeostasis in Bacteria.

Evolutionarily divergent bacteria share a common phenomenological strategy for cell-size homeostasis under steady-state conditions. In the presence of inherent physiological stochasticity, cells following this "adder" principle gradually return to their steady-state size by adding a constant volume between birth and division, regardless of their size at birth. However, the mechanism of the adder has been unknown despite intense efforts.

A Chemical Inhibitor of Cell Growth Reduces Cell Size in Bacillus subtilis.

Bacteria exhibit complex responses to biologically active small molecules. These responses include reductions in transcriptional and translational efficiency, alterations in metabolic flux, and in some cases, dramatic changes in growth and morphology. Here, we describe Min-1, a novel small molecule that inhibits growth of Gram-positive bacteria by targeting the cell envelope.

Host cell perforation by listeriolysin O (LLO) activates a Ca-dependent cPKC/Rac1/Arp2/3 signaling pathway that promotes internalization independently of membrane resealing.

Host cell invasion is an indispensable step for a successful infection by intracellular pathogens. Recent studies identified pathogen-induced host cell plasma membrane perforation as a novel mechanism used by diverse pathogens (, , and adenovirus) to promote their internalization into target cells. It was concluded that and adenovirus damage the host cell plasma membrane to hijack the endocytic-dependent membrane resealing machinery, thereby invading the host cell.

Fatty Acid Availability Sets Cell Envelope Capacity and Dictates Microbial Cell Size.

Nutrients-and by extension biosynthetic capacity-positively impact cell size in organisms throughout the tree of life. In bacteria, cell size is reduced 3-fold in response to nutrient starvation or accumulation of the alarmone ppGpp, a global inhibitor of biosynthesis. However, whether biosynthetic capacity as a whole determines cell size or whether particular anabolic pathways are more important than others remains an open question.

Bacterial Size: Can't Escape the Long Arm of the Law.

Environmental perturbations can lead to changes in bacterial cell size that are not predicted by current models. A recent study presents a model that accurately predicts cell size under a variety of environmental conditions, from just a few measurable variables.

Growth rate and cell size: a re-examination of the growth law.

Research into the mechanisms regulating bacterial cell size has its origins in a single paper published over 50 years ago. In it Schaechter and colleagues made the observation that the chemical composition and size of a bacterial cell is a function of growth rate, independent of the medium used to achieve that growth rate, a finding that is colloquially referred to as 'the growth law'. Recent findings hint at unforeseen complexity in the growth law, and suggest that nutrients rather than growth rate are the primary arbiter of size.

CXCR3 expression defines a novel subset of innate CD8+ T cells that enhance immunity against bacterial infection and cancer upon stimulation with IL-15.

Innate CD8(+) T cells are a heterogeneous population with developmental pathways distinct from conventional CD8(+) T cells. However, their biology, classification, and functions remain incompletely understood. We recently demonstrated the existence of a novel population of chemokine (C-X-C motif) receptor 3 (CXCR3)-positive innate CD8(+) T cells.

Human trophoblasts confer resistance to viruses implicated in perinatal infection.

Objective: Primary human trophoblasts were previously shown to be resistant to viral infection, and able to confer this resistance to nontrophoblast cells. Can trophoblasts protect nontrophoblastic cells from infection by viruses or other intracellular pathogens that are implicated in perinatal infection?

Study Design: Isolated primary term human trophoblasts were cultured for 48-72 hours. Diverse nonplacental human cell lines (U2OS, human foreskin fibroblast, TZM-bl, MeWo, and Caco-2) were preexposed to either trophoblast conditioned medium, nonconditioned medium, or miR-517-3p for 24 hours.

Fluxes of Ca2+ and K+ are required for the listeriolysin O-dependent internalization pathway of Listeria monocytogenes.

Listeria monocytogenes is responsible for the life-threatening food-borne disease listeriosis. This disease mainly affects elderly and immunocompromised individuals, causing bacteremia and meningoencephalitis. In pregnant women, L.

The pore-forming toxin listeriolysin O is degraded by neutrophil metalloproteinase-8 and fails to mediate Listeria monocytogenes intracellular survival in neutrophils.

The pore-forming toxin listeriolysin O (LLO) is a major virulence factor secreted by the facultative intracellular pathogen Listeria monocytogenes. This toxin facilitates L. monocytogenes intracellular survival in macrophages and diverse nonphagocytic cells by disrupting the internalization vesicle, releasing the bacterium into its replicative niche, the cytosol.

The pore-forming toxin listeriolysin O mediates a novel entry pathway of L. monocytogenes into human hepatocytes.

Intracellular pathogens have evolved diverse strategies to invade and survive within host cells. Among the most studied facultative intracellular pathogens, Listeria monocytogenes is known to express two invasins-InlA and InlB-that induce bacterial internalization into nonphagocytic cells. The pore-forming toxin listeriolysin O (LLO) facilitates bacterial escape from the internalization vesicle into the cytoplasm, where bacteria divide and undergo cell-to-cell spreading via actin-based motility.